bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell hydration and mTOR‐dependent signalling
Authors: Schliess F. , Richter L. , Vom Dahl S. , Häussinger D. 
Published: May 2006

AbstractInsulin‐ and amino acid‐induced signalling by the mammalian target of rapamycin (mTOR) involves hyperphosphorylation of the p70 ribosomal S6 protein kinase (p70S6‐kinase) and the eukaryotic initiation factor 4E (eIF4E) binding protein 4E‐BP1 and contributes to regulation of protein metabolism. This review considers the impact of cell hydration on mTOR‐dependent signalling. Although hypoosmotic hepatocyte swelling in some instances activates p70S6‐kinase, the hypoosmolarity‐induced proteolysis inhibition in perfused rat liver is insensitive to mTOR inhibition by rapamycin. Likewise, swelling‐dependent proteolysis inhibition by insulin and swelling‐independent proteolysis inhibition by leucine, a potent activator of p70S6‐kinase and 4E‐BP1 hyperphosphorylation, in perfused rat liver is insensitive to rapamycin, indicating that at least rapamycin‐sensitive mTOR signalling is not involved. Hyperosmotic dehydration in different cell types produces inactivation of signalling components around mTOR, thereby attenuating insulin‐induced glucose uptake, glycogen synthesis, and lipogenesis in adipocytes, and MAP‐kinase phosphatase MKP‐1 expression in hepatoma cells. Direct inactivation of mTOR, stimulation of the AMP‐activated protein kinase, and the destabilization of individual proteins may impair mTOR signalling under dehydrating conditions. Further investigation of the crosstalk between the mTOR pathway(s) and hyperosmotic signalling will improve our understanding about the contribution of cell hydration changes in health and disease and will provide further rationale for fluid therapy of insulin‐resistant states.
The ICln interactome
Authors: Fürst J. , Bottà G. , Saino S. , Dopinto S. , Gandini R. , Dossena S. , Vezzoli V. , Rodighiero S. , Bazzini C. , Garavaglia M. L. , Meyer G. , Jakab M. , Ritter M. , Wappl‐Kornherr E. , Paulmichl M. 
Published: May 2006

AbstractThe many different functional phenotypes described in mammalian cells can only be explained by an intense interaction of the underlying proteins, substantiated by the fact that the number of independently expressed proteins in living cells seems not to exceed 25 K, a number way too small to explain the >250 K different phenotypes on a one‐protein–one‐function base. Therefore, the study of the interactome of the different proteins is of utmost importance. Here, we describe the present knowledge of the ICln interactome. ICln is a protein, we cloned and whose function was reported to be as divers as (i) ion permeation, (ii) cytoskeletal organization, and (iii) RNA processing. The role of ICln in these different functional modules can be described best as being a ‘connector hub’ with ‘date hub’ function.
Functional role of amino terminus in ClC‐3 chloride channel regulation by phosphorylation and cell volume
Authors: Rossow C. F. , Duan D. , Hatton W. J. , Britton F. , Hume J. R. , Horowitz B. 
Published: May 2006

AbstractAim:  This study investigated the functional role of the ClC‐3 amino‐terminus in channel regulation in response to changes in cell volume.Methods:  Wild‐type sClC‐3 tagged with a green fluorescence protein (GFP) at the C‐terminus was used as a template to construct a number of deletion mutants which were functionally expressed in NIH‐3T3 cells. Whole cell and single channel patch‐clamp electrophysiology was used to determine the functional properties of heterologously expressed channels.Results:  The first 100 amino acids of the ClC‐3 N‐terminus were removed and the truncated channel (sClC‐3ΔNT) was functionally expressed. Immunocytochemistry confirmed membrane expression of both wtsClC‐3 and sClC‐3ΔNT channels in NIH/3T3 cells. sClC‐3ΔNT yielded constitutively active functional channels, which showed no response to protein kinase C or changes in cell volume. Deletion of a cluster of negatively charged amino acids 16–21 (sClC‐3Δ16–21) within the N‐terminus also yielded a constitutively active open channel phenotype, indicating these amino acids are involved in the N‐type regulation. Intracellular delivery of a thiol‐phosphorylated peptide corresponding to N‐terminal residues 12–61 (NT peptide) markedly inhibited sClC‐3ΔNT whole‐cell and single‐channel currents, further confirming the essential role of the N‐terminus in volume regulation of channel activity.Conclusions:  These data strongly suggest the N‐terminus of sClC‐3 channels acts as a blocking particle inhibiting the flow of anions through the channel pore. This ‘N‐type’ regulation of sClC‐3 channels may be an important transducing mechanism linking changes in cell volume and channel protein phosphorylation to channel gating.
Normotonic cell shrinkage induces apoptosis under extracellular low Cl− conditions in human lymphoid and epithelial cells
Authors: Maeno E. , Shimizu T. , Okada Y. 
Published: May 2006

AbstractAim:  Sustained cell shrinkage is associated with apoptosis. Apoptotic volume decrease, which is known to be induced by release of osmolytes including Cl− ions, may be an essential event for apoptosis induction. Provided any anion channels and/or anion transporters are basally functioning, there is a possibility that imposition of a driving force for Cl− efflux per se results in sustained cell shrinkage and thereby induces apoptotic death. Here, this possibility was tested by reducing the extracellular Cl− concentration.Methods:  Human lymphoid U937 and epithelial HeLa cells were provided for experiments after exposing to isotonic electrolyte solution which contains 146 or 1 mm Cl−. Measurements of mean cell volume, caspase‐3 activity and cell viability were performed by a Coulter‐type cell size analyzer, a fluorometric assay and a colorimetric assay, respectively.Results:  After exposure to low Cl− solution in which most chloride was replaced with aspartate, gluconate, phosphate or methanesulphonate, both U937 and HeLa cells exhibited, for up to 60 min, shrinkage to a level (90–80%) significantly lower than that in control high Cl− solution. Reduction in cell viability started within 2 h and reached below 20% within 8 h after exposure to low Cl− solution. The cell death was found to be associated with caspase‐3 activation and DNA fragmentation.Conclusions:  Exposure to isotonic low Cl− solution induced sustained shrinkage and thereafter apoptotic death in U937 and HeLa cells. Thus, it is suggested that sustained cell shrinkage per se provides a sufficient condition for apoptosis induction.
Na+/H+ exchangers and the regulation of volume
Authors: Alexander R. T. , Grinstein S. 
Published: May 2006

AbstractThe regulation of volume is fundamental to life. There exist numerous conditions that can produce perturbations of cell volume. The cell has developed mechanisms to directly counteract these perturbations so as to maintain its physiological volume. Directed influx of the major extracellular cation, sodium, serves to counteract a decreased cell volume through the subsequent osmotically coupled movement of water to the intracellular space. This process, termed regulatory volume increase is often mediated by the ubiquitous sodium/hydrogen ion exchanger, NHE1. Similarly, the maintenance of intravascular volume is essential for the maintenance of blood pressure and consequently the proper perfusion of vital organs. Numerous mechanisms exist to counterbalance alterations in intravascular volume, not the least of which is the renal absorption of sodium filtered at the glomerulus. Two‐thirds of filtered sodium and water are absorbed in the renal proximal tubule, a mechanism that intimately involves the apical sodium/hydrogen ion exchanger, NHE3. This isoform is fundamental to the maintenance and regulation of intravascular volume and blood pressure. In this article, the effects of cell volume on the activity of these different isoforms, NHE1 and NHE3, will be described and the consequences of their activity on intracellular and intravascular volume will be explored.
On the mechanism of ionic regulation of apoptosis: would the Na+/K+‐ATPase please stand up?
Authors: Panayiotidis M. I. , Bortner C. D. , Cidlowski J. A. 
Published: May 2006

AbstractApoptosis is an active process with distinct features including loss of cell volume, chromatin condensation, internucleosomal DNA fragmentation, and apoptotic body formation. Among the classical characteristics that define apoptosis, the loss of cell volume has become a very important component of the programmed cell death process. Changes in cell volume result from alterations in the homeostasis of ions and in particular the movement of Na+ and K+ ions. Most living cells have a high concentration of intracellular K+ and a low concentration of intracellular Na+. This is in contrast to the outside of the cell, where there is a high concentration of extracellular Na+ and a low concentration of extracellular K+. Thus a concentration gradient exists for the loss and gain of intracellular K+ and Na+, respectively. This gradient is maintained through the activity of various ionic channels and transporters, but predominantly the activity of the Na+/K+‐ATPase. During apoptosis, there is compelling evidence indicating an early increase in intracellular Na+ followed by a decrease in both intracellular K+ and Na+ suggesting a regulatory role for these cations during both the initial signalling, and the execution phase of apoptosis. Recent studies have shown that the Na+/K+‐ATPase is involved in controlling perturbations of Na+ and K+ homeostasis during apoptosis, and that anti‐apoptotic Bcl‐2 and Bcl‐XL molecules influence these ionic fluxes. Finally, understanding the regulation or deregulation of ionic homeostasis during apoptosis is critical to facilitate the treatment of cardiovascular, neurological, and renal diseases where apoptosis is known to play a major role.
Aquaporins in plants
Authors: Kaldenhoff R. , Fischer M. 
Published: May 2006

AbstractAlthough very often exposed to a rapid changing environment, plants are in general unable to evade from unfavourable conditions. Therefore, a fine tuned adaptation of physiology including the water balance appears to be of crucial importance. As a consequence a relatively large number of aquaporin genes are present in plant genomes. So far aquaporins in plants were shown to be involved in root water uptake, reproduction or photosynthesis. Accordingly, plant aquaporin classification as simple water pores has changed corresponding to their molecular function into channels permeable for water, small solutes and/or gases. An adjustment of the respective physiological process could be achieved by regulation mechanisms, which range from post‐translational modification, molecular trafficking to heteromerization of aquaporin isoforms. Here the function of the four plant aquaporin family subclasses with regard to substrate specificity, regulation and physiological relevance is described.
SPAK and OSR1, key kinases involved in the regulation of chloride transport
Authors: Delpire E. , Gagnon K. B. 
Published: May 2006

AbstractReversible phosphorylation by protein kinases is probably one of the most important examples of post‐translational modification of ion transport proteins. Ste20‐related proline alanine‐rich kinase (SPAK) and oxidative stress response kinase (OSR1) are two serine/threonine kinases belonging to the germinal centre‐like kinase subfamily VI. Genetic analysis suggests that OSR1 evolved first, with SPAK arising following a gene duplication in vertebrate evolution. SPAK and OSR1 are two recently discovered kinases which have been linked to several key cellular processes, including cell differentiation, cell transformation and proliferation, cytoskeleton rearrangement, and most recently, regulation of ion transporters. Na–K–2Cl cotransporter activity is regulated by phosphorylation. Pharmacological evidence has identified several kinases and phosphatases which alter cotransporter function, however, no direct linkage between these enzymes and the cotransporter has been demonstrated. This article will review some of the physical and physiological properties of SPAK and OSR1, and present new evidence of a direct interaction between the Na–K–Cl cotransporter and the stress kinases.
Fluid transport and ion fluxes in mammalian kidney proximal tubule: a model analysis of isotonic transport
Authors: Larsen E. H. , Møbjerg N. , Sørensen J. N. 
Published: May 2006

AbstractAim:  By mathematical modelling, we analyse conditions for near‐isotonic and isotonic transport by mammalian kidney proximal tubule.Methods:  The model comprises compliant lateral intercellular space (lis) and cells, and infinitely large luminal and peritubular compartments with diffusible species: Na+, K+, Cl− and an intracellular non‐diffusible anion. Unknown model variables are solute concentrations, electrical potentials, volumes and hydrostatic pressures in cell and lis, and transepithelial potential. We used data mainly from rat proximal tubule to model epithelial cells and interspace with luminal and peritubular baths of identical composition.Results:  The model of the tubular epithelium with physiological water permeability and paracellular electrical resistance generates solute coupled water uptake with an approx. 3% hypertonic absorbate. This function remains unperturbed following ‘blocking’ of apical water channels and in ‘aquaporin‐null’ simulation. Reduced rate of volume reabsorption in AQP(‐/‐) mice would also require decreased apical sodium permeability. Paracellular convection accounts for approx. 36% of the net Na+ absorption, and the model epithelium accomplishes uphill water transport similar to rat proximal tubule. Na+ recirculation is required for truly isotonic transport. The tonicity of the absorbate and the recirculation flux depend critically on ion permeabilities of interspace basement membrane.Conclusion:  Our model based on solute‐solvent coupling in lateral space simulates major physiological features of proximal tubule, including significantly lower water permeability of the AQP1‐null preparation, and a ratio of net sodium uptake and oxygen consumption exceeding that predicted from stoichiometry of the Na+/K+‐pump. Physical properties of interspace basement membrane are critical for obtaining near‐isotonic and truly isotonic transport.
Nitric oxide in the kidney: functions and regulation of synthesis
Authors: Mount P. F. , Power D. A. 
Published: May 2006

AbstractIn the kidney nitric oxide (NO) has numerous important functions including the regulation of renal haemodynamics, maintenance of medullary perfusion, mediation of pressure–natriuresis, blunting of tubuloglomerular feedback, inhibition of tubular sodium reabsorption and modulation of renal sympathetic neural activity. The net effect of NO in the kidney is to promote natriuresis and diuresis. Significantly, deficient renal NO synthesis has been implicated in the pathogenesis of hypertension. All three isoforms of nitric oxide synthase (NOS), namely neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2) and endothelial NOS (eNOS or NOS3) are reported to contribute to NO synthesis in the kidney. The regulation of NO synthesis in the kidney by NOSs is complex and incompletely understood. Historically, many studies of NOS regulation in the kidney have emphasized the role of variations in gene transcription and translation. It is increasingly appreciated, however, that the constitutive NOS isoforms (nNOS and eNOS) are also subject to rapid regulation by post‐translational mechanisms such as Ca2+ flux, serine/threonine phosphorylation and protein–protein interactions. Recent studies have emphasized the role of post‐translational regulation of nNOS and eNOS in the regulation of NO synthesis in the kidney. In particular, a role for phosphorylation of nNOS and eNOS at both activating and inhibitory sites is emerging in the regulation of NO synthesis in the kidney. This review summarizes the roles of NO in renal physiology and discusses recent advances in the regulation of eNOS and nNOS in the kidney by post‐translational mechanisms such as serine/threonine phosphorylation.
Cellular basis of sex disparities in human cardiac electrophysiology
Authors: Verkerk A. O. , Wilders R. , De Geringel W. , Tan H. L. 
Published: May 2006

AbstractAim: Sex disparities in electrocardiogram variables and dysrhythmia susceptibility exist, notably in long QT syndrome (LQTS) and Brugada syndrome, but the underlying mechanisms in man are unknown. We studied the cellular basis of sex distinctions in human cardiac electrophysiology and dysrhythmia susceptibility using mathematical models of human ventricular myocytes.Methods: We implemented sex differences in the Priebe–Beuckelmann and ten Tusscher–Noble–Noble–Panfilov human ventricular cell models by modifying densities of the L‐type Ca2+current (ICa,L), transient outward K+current (Ito), and rapid delayed rectifier K+current (IKr), according to experimental data from male and female hearts of various species. Sex disparities in transmural repolarization were studied in transmural strands of cells with ion current densities based on canine experimental data.Results: Female cells have longer action potential duration (APD), steeper APD‐heart rate relationship, larger transmural APD heterogeneity, and a greater susceptibility to pro‐dysrhythmogenic early afterdepolarizations (EADs) than male cells. Conversely, male cells have more prominent phase‐1 repolarization and are more susceptible to all‐or‐none repolarization.Conclusion: Sex differences inICa,L,ItoandIKrdensities may explain sex disparities in human cardiac electrophysiology. Female cells exhibit a limited ‘repolarization reserve’ as demonstrated by their larger susceptibility to EADs, which, combined with their larger transmural electrical heterogeneity, renders them more vulnerable to tachydysrhythmias in LQTS. Conversely, male cells have a limited ‘depolarization reserve’, as shown by their larger susceptibility to all‐or‐none repolarization, which facilitates tachydysrhythmias in Brugada syndrome. These general principles may also apply to dysrhythmia susceptibility in common disease.
Overexpression of VEGF‐A induces neovascularization and increased vascular leakage in rabbit eye after intravitreal adenoviral gene transfer
Authors: Kinnunen K. , Korpisalo P. , Rissanen T. T. , Heikura T. , Viita H. , Uusitalo H. , Ylä‐Herttuala S. 
Published: May 2006

AbstractAims:  The aim of this study was to determine dose–response effects of vascular endothelial growth factor A as delivered using an adenoviral vector on vascular growth and pathological changes in the rabbit eye. Moreover, we wanted to develop a large animal model for angioproliferative diseases in the eye.Methods:  Seventeen New Zealand White rabbits were injected with adenoviral vascular endothelial growth factor‐A (AdVEGF‐A) intravitreally with different doses (109–1011 vp). Controls were injected with an empty virus (AdCMV). Some animals had a combination of AdVEGF‐A and AdsKDR (a soluble form of the VEGF receptor‐2). Animals were killed 6 days after the gene transfer. On the basis of these results, 14 rabbits were injected intravitreally with AdVEGF‐A or adenoviral LacZ (AdLacZ) with 1010 vp in a volume of 0.1 mL. Animals were killed 3, 6, 14 and 28 days after the gene transfer, eyes were removed and analysed histologically.Results:  In enzyme‐linked immunosorbent assay (ELISA) analysis, human VEGF‐A was present in vitreous humour in all VEGF‐A transduced eyes. The amount of VEGF‐A showed a dose‐dependent increase with the AdVEGF‐A dose and was the highest 6 days after the gene transfer. Histologic analyses revealed an increased capillary area and density in the AdVEGF‐A eyes when compared with the AdLacZ eyes (P < 0.05). In the AdVEGF‐A/AdsKDR eyes the average capillary area was not increased compared with AdLacZ eyes.Conclusion:  This model could be useful for large animal studies regarding the pathogenesis of neoangiogenesis and for the development of new therapeutic strategies for angioproliferative diseases of the eye. Our results establish the key role of VEGF‐A in the induction of neovascularization and pathological changes in the rabbit eye.
Adsorption Modification of Carboxylated Carbon Nanotubes with Aniline in Aqueous Solution
Authors: Xie Xiaofeng , Gao Lian 
Published: May 2006

Abstract
Aniline-modified multi-walled carbon nanotubes (MWNT) have been obtained through interaction between carboxylated MWNT and aniline in aqueous solution. The influence of three species carboxylation treatment on the interaction has been studied. FT-IR spectra bands detectable in this case implied the generation of amide bonds and the conjugation of aromatic ring in samples. The results show that citric acid serves as super intermediate medium in the course of aniline-modified MWNT. Moreover, higher temperature can promote the modified procedure significantly.
Synthesis of 1,3-Selenazines and 1,3-Selenazolidines via Intramolecular Addition of N-Allylselenoureas
Authors: Koketsu Mamoru , Kiyokuni Takashi , Sakai Tsutomu , Ando Hiromune , Ishihara Hideharu 
Published: May 2006

Abstract
The regiochemistry of intramolecular addition of N-allylselenoureas leading to 2-imino-5-methyl-1,3-selenazolidines or 2-amino-5-iodo-4H-5,6-dihydro-1,3-selenazines depends on the treatment of hydrogen chloride or iodine: treatment of hydrogen chloride with N-allylselenoureas affords preferentially 2-imino-5-methyl-1,3-selenazolidines through 5-endo closure, whereas treatment of iodine affords preferentially 2-amino-5-iodo-4H-5,6-dihydro-1,3-selenazines through 6-exo closure.
Photochromism of Diarylethene-functionalized Polystyrene with High Conversion in a Solid-state Polymer Film
Authors: Kobatake Seiya , Kuratani Hirotsugu 
Published: May 2006

Abstract
Photochromic polymers that exhibit thermally irreversible and photochemically reversible color changes were synthesized by radical polymerization of a styrene monomer having a photochromic diarylethene chromophore. The photocoloration reaction of the polymer proceeded with high conversion even in the solid-state polymer film.
SnCl2·2H2O—An Alternative to Lewis Acidic Ionic Liquids
Authors: Arumugam Pandurangan , Perumal Paramasivan T 
Published: May 2006

Abstract
Inexpensive and commercially available SnCl2·2H2O has been shown to be an alternative to Lewis acidic ionic liquids by carrying out a variety of organic synthesis. The reaction medium is recycleable and the reaction time is comparable with the microwave reactions.
Simultaneous Synthesis and Self-assembly of Cyclic Diphenylalanine at Hydrothermal Condition
Authors: Togashi Takanari , Umetsu Mitsuo , Tsuchizaki Hiroyuki , Ohara Satoshi , Naka Takashi , Adschiri Tadafumi 
Published: May 2006

Abstract
Hydrophobic amino acid, l-phenylalanine, formed insoluble aggregates with unique morphologies at hydrothermal condition. The analyses by infrared spectrum and gel permeation chromatography indicate the highly efficient synthesis of cyclic diphenylalanine probably due to solid–liquid phase separation. The formed cyclic diphenylalanine simultaneously self-assembled to form nanorod structure in the hydrothermal condition.
Construction of a Fuel Cell from Proton-conducting Silica Nanofilm
Authors: Li Haibin , Kunitake Toyoki 
Published: May 2006

Abstract
We constructed a fuel cell using a proton-conducting porous silica film with thickness of 650 nm. This fuel cell delivered an open circuit voltage (OCV) of 540 mV and a maximum power density of 51 μW/cm2 at room temperature. The silanol group on the pore wall promoted proton conduction, and water molecules adsorbed in the pore suppressed permeation of fuel gas.