Segment-specific expression of sodium-phosphate cotransporters NaPi-IIa and -IIc and interacting proteins in mouse renal proximal tubules

Sodium-dependent phosphate cotransport in renal proximal tubules (PTs) is heterogeneous with respect to proximal tubular segmentation (S1 vs. S3) and nephron generation (superficial vs. juxtamedullary). In the present study, S1 and S3 segments of superficial and juxtamedullary nephrons were laser-microdissected and mRNA and protein expression of the Na/Pi-cotransporters NaPi-IIa and NaPi-IIc and the PDZ proteins NHERF-1 and PDZK1 determined. Expression of NaPi-IIa mRNA decreased axially in juxtamedullary nephrons. There was no effect of dietary Pi content on NaPi-lla mRNA expression in any proximal tubular segment. The abundance of the NaPi-IIa cotransporter in the brush-border membrane showed inter- and intranephron heterogeneity and increased in response to a low-Pi diet (5days), suggesting that up-regulation of NaPi-lla occurs via post-transcriptional mechanisms. In contrast, NaPi-IIc mRNA and protein was up-regulated by the low-Pi diet in all nephron generations analysed. NHERF-1 and PDZK1, at both mRNA and protein levels, were distributed evenly along the PTs and did not change after a low-Pi die

AMADEOS SysML Profile for SoS Conceptual Modeling

International audienc

A First Comparison of the responses of a He4-based fast-neutron detector and a NE-213 liquid-scintillator reference detector

A first comparison has been made between the pulse-shape discrimination characteristics of a novel $^{4}$He-based pressurized scintillation detector and a NE-213 liquid-scintillator reference detector using an Am/Be mixed-field neutron and gamma-ray source and a high-resolution scintillation-pulse digitizer. In particular, the capabilities of the two fast neutron detectors to discriminate between neutrons and gamma-rays were investigated. The NE-213 liquid-scintillator reference cell produced a wide range of scintillation-light yields in response to the gamma-ray field of the source. In stark contrast, due to the size and pressure of the $^{4}$He gas volume, the $^{4}$He-based detector registered a maximum scintillation-light yield of 750~keV$_{ee}$ to the same gamma-ray field. Pulse-shape discrimination for particles with scintillation-light yields of more than 750~keV$_{ee}$ was excellent in the case of the $^{4}$He-based detector. Above 750~keV$_{ee}$ its signal was unambiguously neutron, enabling particle identification based entirely upon the amount of scintillation light produced.Comment: 23 pages, 7 figures, Nuclear Instruments and Methods in Physics Research Section A review addresse

Sodium Transport in Capillaries Isolated from Rat Brain

Brain capillary endothelial cells form a bloodbrain barrier (BBB) that appears to play a role in fluid and ion homeostasis in brain. One important transport system that may be involved in this regulatory function is the Na + ,K + -ATPase that was previously demonstrated to be present in isolated brain capillaries. The goal of the present study was to identify additional Na + transport systems in brain capillaries that might contribute to BBB function. Microvessels were isolated from rat brains and 22 Na + uptake by and efflux from the cells were studied. Total 22 Na + uptake was increased and the rate of 22 Na + efflux was decreased by ouabain, confirming the presence of Na + ,K + -ATPase in capillary cells. After inhibition of Na + ,K + -ATPase activity, another saturable Na + transport mechanism became apparent. Capillary uptake of 22 Na + was stimulated by an elevated concentration of Na + or H + inside the cells and inhibited by extracellular Na + , H + , Li + , and NH 4 + . Amiloride inhibited 22 Na + uptake with a K i between 10 −5 and 10 −6 M but there was no effect of 1 mM furosemide on 22 Na + uptake by the isolated microvessels. These results indicate the presence in brain capillaries of a transport system capable of mediating Na + / Na + and Na + /H + exchange. As a similar transport system does not appear to be present on the luminal membrane of the brain capillary endothelial cell, it is proposed that Na + /H + exchange occurs primarily across the antiluminal membrane.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66187/1/j.1471-4159.1983.tb09065.x.pd

Clinical and pathological findings of a fatal systemic capillary leak syndrome (Clarkson Disease)

Systemic capillary leak syndrome (SCLS) is a rare disorder with episodes of hypotension, hypoalbuminemia, and hemoconcentration. During attacks endothelial hyperpermeability results in leakage of plasma proteins into the interstitial space. Attacks vary in severity and may be lethal.A 49-year-old previously healthy man was admitted to hospital for hypovolemic shock, anasarca with pleuropericardial effusion, muscle fatigue, and oliguria occurring after a flu-like syndrome. Laboratory data showed an increase in hematocrit (65%), leucocytes (24.590\u200a\u3bc/L), creatinine (2.5\u200amg/dL), creatine phosphokinase (10.000\u200aU/L), and a decrease in serum albumin (17\u200ag/L) without proteinuria. Immunoglobulins of class G/\u3bb monoclonal gammopathy were detected (1.3\u200ag/L). The initial suspicions addressed to a protein-loosing syndrome or to an effort-related rhabdomyolysis. Initial therapy was based on steroids, albumin, and high molecular weight plasma expanders (hydroxyethyl starch). Because of high hematocrit, phlebotomy was also performed. The patient had complete clinical remission and a diagnosis of SCLS was finally made. He received prophylactic therapy with verapamil and theophylline that was self-stopped for intolerance (hypotension and tachycardia). He had a new crisis 2 days after a physical effort, and was admitted in intensive care unit. The patient died for severe hypovolemic shock with multiorgan failure and sudden cardiac arrest 15 hours after hospital admission. Postmortem investigation revealed massive interstitial edema of main organs with myocardial hyperacute ischemia.Studies on SCLS are limited for the rarity of the disease and its unpredictable course. Both prophylactic and acute crisis treatments are empirical and optimal management of severe attacks is still lacking

Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sjögren's syndrome

BACKGROUND: the classification criteria for primary Sjögren's syndrome (pSS) include a number of oral components. In this study we evaluated if salivary flow and composition as well as dental caries are oral markers of disease severity in pSS. METHODS: in 20 patients fulfilling the American-European Consensus criteria for pSS and 20 age-matched healthy controls whole and parotid saliva flow rates and composition, measures of oral dryness, scores of decayed, missing and filled tooth surfaces (DMFS), periodontal indices, oral hygiene, and dietary habits were examined. RESULTS: in pSS, salivary flow rates, pH, and buffer capacities were lower, and DMFS, salivary sodium and chloride concentrations higher than in the healthy controls. DMFS also correlated inversely to salivary flow rates and positively to oral dryness. Apart from slightly increased gingival index, and more frequent dental visits in pSS, the periodontal condition, oral hygiene or sugar intake did not differ between these two groups. In pSS, findings were correlated to labial salivary gland focus score (FS) and presence of serum-autoantibodies to SSA/SSB (AB). The patients having both presence of AB and the highest FS (>2) also had the highest salivary sodium and chloride concentrations, the lowest salivary phosphate concentrations, lowest salivary flow rates, and highest DMFS compared to those with normal salivary concentrations of sodium and chloride at a given flow rate. CONCLUSION: the salivary changes observed in some pSS patients reflect impaired ductal salt reabsorption, but unaffected acinar transport mechanisms, despite low salivary secretion. Our results suggest that changes in salivary flow and composition as well as dental caries may serve as potential markers of the extent of autoimmune-mediated salivary gland dysfunction in pSS. The study also indicates that the ductal epithelium is functionally affected in some pSS patients, which calls for future pathophysiological studies on the mechanisms underlying this impaired salt reabsorption

A randomised controlled trial investigating motor skill training as a function of attentional focus in old age

BACKGROUND: Motor learning research has had little impact on clinical applications and rarely extended to research about how older adults learn motor skills. There is consistent evidence that motor skill performance and learning can be enhanced by giving learners instructions that direct their attention. The aim of this study was to test whether elderly individuals that receive an external focus instruction during training of dynamic balance skills would learn in a different manner compared to individuals that received an internal focus instruction. METHODS: This randomised trial included 26 older persons (81 +/- 6 years) that were training functional balance twice a week for the duration of 5 weeks. Learning outcomes were recorded after every training session. Weight shifting score and dynamic balance parameters (Biodex Balance System), components of the Extended Timed-Get-Up-and-Go test, five chair rises, and falls efficacy (FES-I) was assessed at baseline and post-intervention. RESULTS: Participation for training sessions was 94%. No differences between groups were found following 5 weeks of training for weight shifting score, dynamic balance index and dynamic balance time (p < 0.95, p = 0.16, p < 0.50), implying no learning differences between training groups. Extended Timed-Get-Up-and-Go components Sit-to-stand, p = .036; Gait initiation, p = .039; Slow down, stop, turnaround, and sit down, p = 0.011 and the Fes-I (p = 0.014) showed improvements for the total group, indicating that function improved compared to baseline. CONCLUSION: A 5-week balance training improved weight shifting scores and dynamic balance parameters as well as functional abilities. The observed improvements were independent from the type of attentional focus instructions. The findings provide support for the proposition of different motor learning principles in older adults compared to younger adults

Optostimulation of striatonigral terminals in substantia nigra induces dyskinesia that increases after L‐DOPA in a mouse model of Parkinson's disease

Background and Purpose: L-DOPA-induced dyskinesia (LID) remains a major complication of L-DOPA therapy in Parkinson's disease. LID is believed to result from inhibition of substantia nigra reticulata (SNr) neurons by GABAergic striatal projection neurons that become supersensitive to dopamine receptor stimulation after severe nigrostriatal degeneration. Here, we asked if stimulation of direct medium spiny neuron (dMSN) GABAergic terminals at the SNr can produce a full dyskinetic state similar to that induced by L-DOPA. Experimental Approach: Adult C57BL6 mice were lesioned with 6-hydroxydopamine in the medial forebrain bundle. Channel rhodopsin was expressed in striatonigral terminals by ipsilateral striatal injection of adeno-associated viral particles under the CaMKII promoter. Optic fibres were implanted on the ipsilateral SNr. Optical stimulation was performed before and 24 hr after three daily doses of L-DOPA at subthreshold and suprathreshold dyskinetic doses. We also examined the combined effect of light stimulation and an acute L-DOPA challenge. Key Results: Optostimulation of striatonigral terminals inhibited SNr neurons and induced all dyskinesia subtypes (optostimulation-induced dyskinesia [OID]) in 6-hydroxydopamine animals, but not in sham-lesioned animals. Additionally, chronic L-DOPA administration sensitised dyskinetic responses to striatonigral terminal optostimulation, as OIDs were more severe 24 hr after L-DOPA administration. Furthermore, L-DOPA combined with light stimulation did not result in higher dyskinesia scores than OID alone, suggesting that optostimulation has a masking effect on LID. Conclusion and Implications: This work suggests that striatonigral inhibition of basal ganglia output (SNr) is a decisive mechanism mediating LID and identifies the SNr as a target for managing LID.Fil: Keifman, Ettel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Consejo Superior de Investigaciones Científicas; EspañaFil: Ruiz De Diego, Irene. Consejo Superior de Investigaciones Científicas; EspañaFil: Pafundo, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Paz, Rodrigo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Solís, Oscar. Consejo Superior de Investigaciones Científicas; EspañaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Moratalla, Rosario. Consejo Superior de Investigaciones Científicas; Españ

Localization and Functional Characterization of the Rat Oatp4c1 Transporter in an In Vitro Cell System and Rat Tissues

The organic anion transporting polypeptide 4c1 (Oatp4c1) was previously identified as a novel uptake transporter predominantly expressed at the basolateral membrane in the rat kidney proximal tubules. Its functional role was suggested to be a vectorial transport partner of an apically-expressed efflux transporter for the efficient translocation of physiological substrates into urine, some of which were suggested to be uremic toxins. However, our in vitro studies with MDCKII cells showed that upon transfection rat Oatp4c1 polarizes to the apical membrane. In this report, we validated the trafficking and function of Oatp4c1 in polarized cell systems as well as its subcellular localization in rat kidney. Using several complementary biochemical, molecular and proteomic methods as well as antibodies amenable to immunohistochemistry, immunofluorescence, and immunobloting we investigated the expression pattern of Oatp4c1 in polarized cell systems and in the rat kidney. Collectively, these data demonstrate that rat Oatp4c1 traffics to the apical cell surface of polarized epithelium and localizes primarily in the proximal straight tubules, the S3 fraction of the nephron. Drug uptake studies in Oatp4c1-overexpressing cells demonstrated that Oatp4c1-mediated estrone-3-sulfate (E3S) uptake was pH-dependent and ATP-independent. These data definitively demonstrate the subcellular localization and histological location of Oatp4c1 and provide additional functional evidence that reconciles expression-function reports found in the literature

Designing Hybrid Gifts

Hybrid gifting combines physical artefacts and experiences with digital interactivity to generate new kinds of gifts. Our review details how gifting is a complex social phenomenon and how digital gifting is less engaging than physical gifting for both givers and receivers. Employing a Research Through Design approach, we developed a portfolio of four hybrid gifting experiences: an augmented advent calendar; edible music tracks; personalised museum tours; and a narrated city walk. Our reflection addresses three concepts: hybrid wrapping where physical gifts become wrapped in digital media and vice versa; the importance of effortful interactions that are visible and pleasurable; and the need to consider social obligation, including opportunities for acknowledgement and reciprocation, dealing with embarrassment, and recognising the distinction between giving and sharing. Our concepts provide guidance to practitioners who wish to design future gifting experiences while helping HCI researchers engage with the concept of gifting in a nuanced way