Adenosine transport in cultured human umbilical vein endothelial cells (HUVEC) was characterized and shown to be mediated by a single facilitated diffusion mechanism. Initial rates of adenosine influx at 22 degrees C were saturable [apparent Michaelis constant, 69 +/- 10 mu M; maximum velocity (V-max), 600 +/- 70 pmol.10(6) cells(-1).s(-1)] and inhibited by nitrobenzylthioinosine (NBMPR). Formycin B had an unusually high affinity [inhibitory constant K-i), 18 +/- 4.3 mu M], whereas inosine had a low affinity (K-i, 440 (...) +/- 68 mu M) and nucleobases were without effect on adenosine influx. The number of transporters (1.2 x 10(6) sites/cell) was estimated by NBMPR equilibrium binding (apparent dissociation constant, 0.11 +/- 0.01 nM; maximum binding, 2.0 +/- 0.15 pmol/10(6) cells). In addition, we compared these endothelial cells with those obtained from cords from pregnancies complicated by diabetes (HUVEC-D), since embriopathy may occur in these conditions. HUVEC-D exhibited a 2.3-fold reduction in both the V-max for adenosine influx and the maximum number of NBMPR binding sites (260 +/- 40 pmol.10(6) cells(-1).s(-1) and 0.86 +/- 0.08 pmol/10(6) cells, respectively). However, the turnover number for each nucleoside transporter in normal and diabetic HUVEC was similar (approximate to 300 adenosine molecules/s). Adenosine metabolism at 10 mu M in HUVEC-D was modified compared with normal cells. Intracellular phosphorylation (> 90%) was the predominant pathway in normal HUVEC, whereas in HUVEC-D, substantial levels of adenine and adenosine were detected. The present results demonstrate therefore the downregulation of the NBMPR-sensitive nucleoside transporter and changes in adenosine metabolism in HUVEC from diabetic pregnancies. (shrink)

Polyclonal antibodies raised against the human erythrocyte nucleoside transporter were used to investigate the distribution of the nucleoside transporters in the placenta. Immunoblots of brush-border membranes isolated from the human syncytiotrophoblast revealed a cross-reactive species that co-migrated with the erythrocyte nucleoside transporter as a broad band of apparent M 55,000. In contrast, no labelling was detected in basal membranes containing a similar number of equilibrative nucleoside transporters as assessed by nitrobenzylthioinosine -binding. The absence of cross-reactive epitopes in basal membranes and (...) their presence in brush-border membranes was confirmed by confocal immunofluorescence microscopy. The results suggest that at least two isoforms of the NBMPR-sensitive nucleoside transporter are present in the human placenta. The lumenal surfaces of fetal capillaries, small placental vessels and umbilical vein ware also strongly labelled by the antibody, a finding that suggests that the high fetal-placental adenosine uptake previously reported is due to endothelial transporters. (shrink)

Citrate, an organic trivalent anion, is a major substrate for generation of energy in most cells. It is produced in mitochondria and used either in the Krebs' cycle or released into cytoplasm through a specific mitochondrial carriers. Citrate can also be taken up from blood through different plasma membrane transporters. In the cytoplasm, citrate can be used ultimately for fatty acid synthesis, which is increased in cancer cells. Here, we review the ways in which citrate can be transported (...) and discuss the changes in transport and metabolism that occur in cancer cells. The primary focus is on the prostate gland, which is known to produce and release large amounts of citrate during its normal secretory function. The significant changes that occur in citrate‐related metabolism and transport in prostate cancer are the second focus. This review strives to relate these mechanisms to molecular biology on the one hand and to clinical applications on the other. (shrink)

This review explores the hypothesis that regulation of nucleocytoplasmic shuttling is a means of driving differentiation, using spermatogenesis as a model. The transition from undifferentiated spermatogonial stem cell to terminally differentiated spermatozoon is, at its most basic, a change in the repertoire of expressed genes. To effect this, the complement of nuclear proteins, such as transcription factors and chromatin remodelling components must change. Current knowledge of the nuclear proteins and nucleocytoplasmic transport machinery relevant to spermatogenesis is consolidated in this (...) review, and their functional linkages are highlighted not only as a means of regulating nuclear protein composition, but also as a key mechanism regulating gene transcription and hence cell fate. Through this, we hypothesize that male germ cell differentiation is mediated through regulation of nuclear transport machinery components, and thereby of the access of critical factors to the nucleus. The importance of nucleocytoplasmic trafficking to male germ cell differentiation is discussed, using the sex-determining factors Sry and SOX9, cell cycle regulators, CREM and cofactors and the Smads as specific examples, together with the roles in gametogenesis for particular nuclear transport factors in Caenorhabditis elegans and Drosophila. BioEssays 27:1011–1025, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Depletion of mitochondrial endo/exonuclease G‐like (EXOG) in cultured neonatal cardiomyocytes stimulates mitochondrial oxygen consumption rate (OCR) and induces hypertrophy via reactive oxygen species (ROS). Here, we show that neurohormonal stress triggers cell death in endo/exonuclease G‐like‐depleted cells, and this is marked by a decrease in mitochondrial reserve capacity. Neurohormonal stimulation with phenylephrine (PE) did not have an additive effect on the hypertrophic response induced by endo/exonuclease G‐like depletion. Interestingly, PE‐induced atrial natriuretic peptide (ANP) gene expression was completely abolished in (...) endo/exonuclease G‐like‐depleted cells, suggesting a reverse signaling function of endo/exonuclease G‐like. Endo/exonuclease G‐like depletion initially resulted in increased mitochondrial OCR, but this declined upon PE stimulation. In particular, the reserve capacity of the mitochondrial respiratory chain and maximal respiration were the first indicators of perturbations in mitochondrial respiration, and these marked the subsequent decline in mitochondrial function. Although pathological stimulation accelerated these processes, prolonged EXOG depletion also resulted in a decline in mitochondrial function. At early stages of endo/exonuclease G‐like depletion, mitochondrial ROS production was increased, but this did not affect mitochondrial DNA (mtDNA) integrity. After prolonged depletion, ROS levels returned to control values, despite hyperpolarization of the mitochondrial membrane. The mitochondrial dysfunction finally resulted in cell death, which appears to be mainly a form of necrosis. In conclusion, endo/exonuclease G‐like plays an essential role in cardiomyocyte physiology. Loss of endo/exonuclease G‐like results in diminished adaptation to pathological stress. The decline in maximal respiration and reserve capacity is the first sign of mitochondrial dysfunction that determines subsequent cell death. (shrink)

A major problem in the treatment of cancer is the specific targeting of anti‐tumor drugs to these abnormal cells. Ideally, such a drug should act over short distances to minimize damage to healthy cells, and target subcellular compartments that have the highest sensitivity to the drug. Photosensitizers, alpha‐emitting radionuclides and many other medicines could be considered as such drugs if they possessed cellular and subcellular specificity. The author describes a novel approach of using modular recombinant transporters to target (...) photosensitizers and alpha‐emitting radionuclides to the nucleus, where their action is most pronounced, of cancer cells. Photosensitizer‐transporter conjugates have up to 3000 times greater efficacy than free photosensitizers and display cell specificity in contrast to free photosensitizers. Alpha‐emitting radionuclides, conjugated with the modular transporters, acquired similar properties. The different modules of the transporters are interchangeable, meaning that they can be tailored for particular applications. BioEssays 30:278–287, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The rate‐limiting step in the uptake and metabolism of Dglucose by insulin target cells is thought to be glucose transport mediated by glucose transporters (primarily the GLUT4 isoform) localized to the plasma membrane. However, subcellular fractionation, photolabelling and immunocytochemical studies have shown that the pool of GLUT4 present in the plasma membrane is only one of many subcellular pools of this protein. GLUT4 has been found in occluded vesicles at the plasma membrane, clathrin‐coated pits and vesicles, early endosomes, (...) and tubulo‐vesicular structures; the latter are analogous to known specialized secretory compartments. Tracking the movement of GLUT4 through these compartments, and defining the mechanism and site of action of insulin in stimulating this subcellular trafficking, are major topics of current investigation. Recent evidence focuses attention on the exocytosis of GLUT4 as the major site of insulin action. Increased exocytosis may be due to decreased retention of glucose transporters in an intracellular pool, or possibly to increased assembly of a vesicle docking and fusion complex. Although details are unknown, the presence in GLUT4 vesicles of a synaptobrevin homologue leads us to propose that a process analogous to that occurring in synaptic vesicle trafficking is involved in the assembly of GLUT4 vesicles into a form suitable for fusion with the plasma membrane. Evidence that the pathways of signalling from the insulin receptor and of GLUT4 vesicle exocytosis may converge at the level of the key signalling enzyme, phosphatidylinositol 3‐kinase, is discussed. (shrink)

Imagine cells that live in a high‐gradient magnetic field (HGMF). Through what mechanisms do the cells sense a non‐uniform magnetic field and how such a field changes the cell fate? We show that magnetic forces generated by HGMFs can be comparable to intracellular forces and therefore may be capable of altering the functionality of an individual cell and tissues in unprecedented ways. We identify the cellular effectors of such fields and propose novel routes in cell biology predicting new (...) biological effects such as magnetic control of cell‐to‐cell communication and vesicle transport, magnetic control of intracellular ROS levels, magnetically induced differentiation of stem cells, magnetically assisted cell division, or prevention of cells from dividing. On the basis of experimental facts and theoretical modeling we reveal timescales of cellular responses to high‐gradient magnetic fields and suggest an explicit dependence of the cell response time on the magnitude of the magnetic field gradient. (shrink)

Among emotions, surprise has been extensively studied in psychology. In linguistics, surprise, like other emotions, has mainly been studied through the syntactic patterns involving surprise lexemes. However, little has been done so far to correlate the reaction of surprise investigated in psychological approaches and the effects of surprise on language. This cross-disciplinary volume aims to bridge the gap between emotion, cognition and language by bringing together nine contributions on surprise from different backgrounds - psychology, human-agent interaction, linguistics. Using different methods (...) at different levels of analysis, all contributors concur in defining surprise as a cognitive operation and as a component of emotion rather than as a pure emotion. Surprise results from expectations not being met and is therefore related to epistemicity. Linguistically, there does not exist an unequivocal marker of surprise. Surprise may be either described by surprise lexemes, which are often associated with figurative language, or it may be expressed by grammatical and syntactic constructions. Originally published as a special issue of Review of Cognitive Linguistics 13:2 (2015). (shrink)

This article summarizes the study of anion exchange mechanisms in bacteria. Along with defining at least two different families of anion exchange, an examination of such carrier‐mediated antiport reactions has led to techniques that considerably broaden the scope of biochemical methods for examining membrane proteins. Such advances have been exploited to show that anion exchange itself forms the mechanistic base of an entirely new kind of proton pump, one which may shed light on a variety of bacterial events, including methanogenesis. (...) Perhaps most important, the study of exchange provided the final link in a chain of evidence pointing to a structural [rhythm] that seems to characterize membrane carriers. These three issues ‐ a biochemical tool, a new proton pump, and a common structural rhythm ‐ are briefly examined in the context of their origins in the analysis of bacterial anion exchange. (shrink)

Organelles transported along microtubules are normally moved to precise locations within cells. For example, synaptic vesiceles are transported to the neruronal synapse, the Golgi apparatus is generally found in a perinuclear location, and the membranes of the endoplasmic reticulum are actively extended to the cell periphery. The correct positioning of these organelles depends on microtubules and microtubule motors. Melanophores provide an extreme example of organized organelle transport. These cells are specialized to transport pigment granules, which are (...) coordinately moved towards or away from the cell center, and result in the cell appearing alternately light or dark. Melanophores have proved to be an ideal system for studying the mechanisms by which the cell controls the direction of its organelle transport. Pigment granule dispersion (the movement away from the cell center) requires protein phosphorylation, while pigment aggregation (the movement towards the cell center) requires protein dephosphorylation. The target of this phosphorylation and dephosphorylation event is a protein that interacts with the microtubule motor protein, kinesin. Thus, the direction of organelle transport along microtubules may be regulated by controlling the activity of a microtubule motor. (shrink)

This study presents a sociological profile of Peruvian female industrialists and some narratives of their struggle for personal independence and entrepreneurial success within the context of global restructuring and local deindustrialization. The study adopts the classical definition of woman's economic independence as a result of women's participation in the world of paid labor.

Surprise is treated as an affect in Aristotelian philosophy as well as in Cartesian philosophy. In experimental psychology, surprise is considered to be an emotion. In phenomenology, it is only addressed indirectly (Husserl, Heidegger, Levinas), with the important exception of Ricoeur and Maldiney; it is reduced to a break in cognition by cognitivists (Dennett). Only recently was it broached in linguistics, with a focus on lexico-syntactic categories. As for the expression of surprise, it has been studied in connection with evidentiality (...) in languages that encode surprise morphosyntactically. However, how surprise is encoded in languages that lack an evidential morphosyntactic system has been largely unexplored. This book provides new insights into the dynamics of surprise based on a heuristic hypothesis tested against the investigation of time, language and emotion. It is intended to arouse the interest of a multidisciplinary audience keen on crossing the disciplinary borders of phenomenology, cognitive sciences, and pragmatics. The theoretical approaches adopted in this collection of articles rely on experiments and corpus data. They advance knowledge by building on robust empirical results coming from psychology, microphenomenology, linguistics and physiology. (shrink)

Most of the essential cellular components, like nucleic acids, lipids and sugars, are phosphorylated. The phosphate equilibrium in Escherichia coli is regulated by the phosphate (Pi) input from the surrounding medium. Some 90 proteins are synthesized at an increased rate during Pi starvation and the global control of the cellular metabolism requires cross‐talk with other regulatory mechanisms. Since the Pi concentration is normally low in E. coli's natural habitat, these cells have devised a mechanism for synthesis of about 15 (...) proteins to accomplish two specific functions: transport of Pi and its intracellular regulation. The synthesis of these proteins is controlled by two genes (the phoB‐phoR operon), involving both negative and positive functions. PhoR protein is a histidine protein kinase, induced in Pi starvation and is a transmembrane protein. It phosphorylates the regulator protein PhoB which is also Pi starvation‐induced. The PhoB phosphorylated form binds specifically to a DNA sequence of 18 nucleotides (the pho Box), which is part of the promoters of the Pho genes. The genes controlled by phoB constitute the Pho regulon.The repression of phoA (the gene encoding alkaline phosphatase) by high Pi concentrations in the medium requires the presence of an intact Pst operon (pstS, pstC, pstA, pstB and phoU) and phoR. The products of pstA and pstC are membrane bound, whereas the product of pstS is periplasmic and PstB and PhoU proteins are cytoplasmic. The function of the PhoU protein may be regulated by cofactor nucleotides and may be involved in signaling the activation of the regulon via PhoR. (shrink)

When cells are starved of their substrate, many nutrient transporters are induced. These undergo rapid endocytosis and redirection of their intracellular trafficking when their substrate becomes available again. The discovery that some of these transporters also act as receptors, or transceptors, suggests that at least part of the sophisticated controls governing the trafficking of these proteins has to do with their signaling function rather than with control of transport. In yeast, the general amino acid permease Gap1 mediates signaling (...) to the protein kinase A pathway. Its endocytic internalization and intracellular trafficking are subject to amino acid control. Other nutrient transceptors controlling this signal transduction pathway appear to be subject to similar trafficking regulation. Transporters with complex regulatory control have also been suggested to function as transceptors in other organisms. Hence, precise regulation of intracellular trafficking in nutrient transporters may be related to the need for tight control of nutrient‐induced signaling. (shrink)

Extracellular ATP released from necrotic cells in inflamed tissues activates the P2X7 receptor, stimulates the exposure of phosphatidylserine, and causes cell lysis. Recent findings indicated that XK, a paralogue of XKR8 lipid scramblase, forms a complex with VPS13A at the plasma membrane of T cells. Upon engagement by ATP, an unidentified signal(s) from the P2X7 receptor activates the XK‐VPS13A complex to scramble phospholipids, followed by necrotic cell death. P2X7 is expressed highly in CD25+CD4+ T cells but weakly (...) in CD8+ T cells, suggesting a role of this system in the activation of the immune system to prevent infection. On the other hand, a loss‐of‐function mutation in XK or VPS13A causes neuroacanthocytosis, indicating the crucial involvement of XK‐VPS13A‐mediated phospholipid scrambling at plasma membranes in the maintenance of homeostasis in the nervous and red blood cell systems. (shrink)

Most lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic αβ chains associated with invariant CD3‐γδε components and ζ chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4+CD8+ thymocytes expressing only 10% of the number of αβ TCR complexes on their surfaces expressed by mature CD4+ and CD8+ T cells. (...) Recent evidence demonstrates that low surface TCR density on CD4+CD8+ thymocytes results from the limited survival of a single TCR component within the ER, the TCRα chain, which has a half life of only 15 minutes in immature thymocytes, compared to >75 minutes in mature T cells. Instability of TCRα proteins in immature CD4+CD8+ thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of αβ TCR complexes in CD4+CD8+ thymocytes and comment on the functional significance of TCRα instability during T cell development. (shrink)

In this article, a number of future energy visions, especially those basing the energy systems on hydrogen, are discussed. Some often missing comparisons between alternatives, from a sustainability perspective, are identified and then performed for energy storage, energy transportation, and energy use in vehicles. It is shown that it is important to be aware of the losses implied by production, packaging, distribution, storage, and end-use of hydrogen when suggesting a “hydrogen economy.” It is also shown that for stationary electric energy (...) storage, fuel cell electrolyzers could be feasible. Zero-tailpipeemission vehicles are compared. The battery electric vehicle has the highest electrical efficiency, but other requirements imply that plug-in hybrids or fuel cell hybrids might be a better option in some types of vehicles. Finally, a simplified example is applied to the overall results and used to discuss the needs and nature of an energy system based on intermittent energy sources. (shrink)

The transport of molecules across the nuclear envelope plays a central role in the metabolism of the cell. Significant advances hi three major areas highlight the limits of our current knowledge and point to the prospect of exciting future developments. Firstly, findings that ions and small proteins do not diffuse freely into the nucleus call into question the current views of nuclear envelope permeability. Secondly, indications that nuclear protein import can be regulated in conjunction with the cell cycle and (...) development have been confirmed by the clear demonstration of regulated nuclear entry of specific transcription factors and morphogens. Thirdly, identification and characterisation of candidate receptor proteins indicates that the recognition of the nuclear targeting sequence occurs in the cytoplasm, suggesting that a different recognition event occurs at the nuclear pore. (shrink)

In the 4 1/2 to 5 days between fertilization and implantation, the mouse conceptus must gain the abilities to implant and produce an embryo. Each of these is the sole developmental responsibility of one of two cell types forming the blastocyst, trophectoderm and inner cell mass (ICM), respectively. Trophectoderm is a polarized transporting epithelium while the ICM is an aggregate of non‐epithelial pluripotent stem cells. These two cell types originate from the division of polar blastomeres when their cleavage furrows (...) parallel their apical surfaces. Blastomeres polarize in response to asymmetric cell–cell contact, and understanding the mechanism of this induction is regarded as the key to understanding the origin of trophectoderm and ICM. Here we propose a model based on transcellular ion current loops for the induction of cell polarity during the development of the first epithelium, trophectoderm. (shrink)

It has become customary to conceptualize the living cell as an intricate piece of machinery, different to a man-made machine only in terms of its superior complexity. This familiar understanding grounds the conviction that a cell's organization can be explained reductionistically, as well as the idea that its molecular pathways can be construed as deterministic circuits. The machine conception of the cell owes a great deal of its success to the methods traditionally used in molecular biology. However, the recent introduction (...) of novel experimental techniques capable of tracking individual molecules within cells in real time is leading to the rapid accumulation of data that are inconsistent with an engineering view of the cell. This paper examines four major domains of current research in which the challenges to the machine conception of the cell are particularly pronounced: cellular architecture, protein complexes, intracellular transport, and cellular behaviour. It argues that a new theoretical understanding of the cell is emerging from the study of these phenomena which emphasizes the dynamic, self-organizing nature of its constitution, the fluidity and plasticity of its components, and the stochasticity and non-linearity of its underlying processes. (shrink)

The development of synthetic biology calls for accurate understanding of the critical functions that allow construction and operation of a living cell. Besides coding for ubiquitous structures, minimal genomes encode a wealth of functions that dissipate energy in an unanticipated way. Analysis of these functions shows that they are meant to manage information under conditions when discrimination of substrates in a noisy background is preferred over a simple recognition process. We show here that many of these functions, including transporters and (...) the ribosome construction machinery, behave as would behave a material implementation of the informationmanaging agent theorized by Maxwell almost 150 years ago and commonly known as Maxwell’s demon (MxD). A core gene set encoding these functions belongs to the minimal genome required to allow the construction of an autonomous cell. These MxDs allow the cell to perform computations in an energy-efficient way that is vastly better than our contemporary computers. (shrink)

Spontaneous polarization without spatial cues, or symmetry breaking, is a fundamental problem of spatial organization in biological systems. This question has been extensively studied using yeast models, which revealed the central role of the small GTPase switch Cdc42. Active Cdc42‐GTP forms a coherent patch at the cell cortex, thought to result from amplification of a small initial stochastic inhomogeneity through positive feedback mechanisms, which induces cell polarization. Here, I review and discuss the mechanisms of Cdc42 activity self‐amplification and dynamic turnover. (...) A robust Cdc42 patch is formed through the combined effects of Cdc42 activity promoting its own activation and active Cdc42‐GTP displaying reduced membrane detachment and lateral diffusion compared to inactive Cdc42‐GDP. I argue the role of the actin cytoskeleton in symmetry breaking is not primarily to transport Cdc42 to the active site. Finally, negative feedback and competition mechanisms serve to control the number of polarization sites. (shrink)

JIPs are JNK interacting proteins and bind to JNK cascade kinases. JIP1 and JIP3 were known to be adaptors linking cargo to Kinesin‐I, a major molecular motor for axonal transport. Recent research sheds further light on JIPs' complex roles in axonal transport, namely in activation of Kinesin‐I and in cargo release. In Drosophila, APLIP1/JIP1 allows the Kinesin‐I complex to enable cargo release through activation of JNK signaling.1 In mammalian cell culture, JIP1 is necessary and, together with UNC‐76/FEZ1, sufficient (...) for activating Kinesin‐I.2 I discuss and compare the many roles played by JIP1 and JIP3 through interactions with several distinct players, in retrograde as well as anterograde transport. BioEssays 30:10–14, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

The cilium/flagellum is a sensory-motile organelle ancestrally present in eukaryotic cells. For assembly cilia universally rely on intraflagellar transport (IFT), a specialised bidirectional transport process mediated by the ancestral and conserved IFT complex. Based on the homology of IFT complex proteins to components of coat protein I (COPI) and clathrin-coated vesicles, we propose that the non- vesicular, membrane-bound IFT evolved as a specialised form of coated vesicle transport from a protocoatomer complex. IFT thus shares common ancestry (...) with all protocoatomer derivatives, including all vesicle coats and the nuclear pore complex (NPC). This has major implications for the evolutionary origin of the cilium. First, it reinforces the tenet that duplication and divergence of pre-existing structures, rather than symbiosis, were the major themes during cilium evolution. Second, it suggests that the initial step in the autogenous origin of the cilium was the establishment of a membrane patch with transmembrane proteins transported by the ancestral vesicle-coating IFT complex. We propose a scenario for how the initial membrane patch gradually protruded to enhance exposure to the environment, then started to move, and finally compartmentalised to render receptor signalling and ciliary beating more efficient. BioEssays 28: 191–198, 2006. © 2006 Wiley periodicals, Inc. (shrink)

The recent development of RNA replicating protocells and capsules that enclose complex biosynthetic cascade reactions are encouraging signs that we are gradually getting better at mastering the complexity of biological systems. The road to truly cellular compartments is still very long, but concrete progress is being made. Compartmentalization is a crucial natural methodology to enable control over biological processes occurring within the living cell. In fact, compartmentalization has been considered by some theories to be instrumental in the creation of life. (...) With the advancement of chemical biology, artificial compartments that can mimic the cell as a whole, or that can be regarded as cell organelles, have recently received much attention. The membrane between the inner and outer environment of the compartment has to meet specific requirements, such as semi‐permeability, to allow communication and molecular transport over the border. The membrane can either be built from natural constituents or from synthetic polymers, introducing robustness to the capsule. (shrink)

Hydrogen fuel cells are likely to begin replacing conventional internal combustion engines as a power generation method for transportation applications in the near future. A life cycle analysis of a hydrogen fuel cell was performed to examine the major environmental impacts of such an engine in comparison with an internal combustion engine. To quantify the emissions, material consumption and energy consumption were identified by carrying out mass and energy balances, respectively. Wherever possible, a “well-to-wheel” approach was adopted to identify (...) all the processes involved. The size of the hydrogen fuel cell engine selected was 60 kW, which would power a small automobile weighing around 800 kg. This report briefly describes the materials and processes involved in assembling such an engine, with their respective environmental impacts. Different technologies to build a hydrogen economy also are discussed because hydrogen is an integral part of most fuel cell engines. The main conclusion is that if an environmentally sustainable system of hydrogen production is found, the use of hydrogen and, in turn, hydrogen fuel cell cars would be highly beneficial. Thus, the theoretical potential of fuel cells is great for environmental benefits, but practical applications might prove otherwise. (shrink)

This paper presents its author's famous distinction between globalization, as the process or vehicle by which ideas, habits and worldviews travel from one culture to another and are transformed in the process, and mundialization, as the taking in of the outside world into our own lifeworlds, a process by which the ideas and customs of other cultures are transported into our homeworlds. In this process, what was once strange and unfamiliar is transformed into something comfortable and familiar. This is the (...) process that is generally known as cultural assimilation, and by virtue of which the boundaries of our individual homeworlds become constantly widened. Examining this phenomenon, which he calls the 'mundialization of home', leads the author to sketch the main features of a possible transcultural moral world. (shrink)

Many biologically active compounds including neurotransmitters, metabolic precursors, and certain drugs are accumulated intracellularly by transporters that are coupled to the transmembrane Na+ gradient. Amino acid neurotransmitter transporters play a key role in the regulation of extracellular amino acid concentrations and termination of neurotransmission in the CNSAbbreviations: CNS, central nervous system; GABA, γ‐aminobutyric acid; cDNA, complementary deoxyribonucleic acid; mRNA, messenger ribonucleic acid; NMDA, N‐methyl‐D‐aspartate; PKC, protein kinase C; PMA, phorbol 12‐myristate 13‐acetate; DAG, diacyl glycerol; R59022, DAG kinase inhibitor; AA, arachidonic (...) acid; ACHC, cis‐3‐aminocyclohexanecarboxylic acid; GAT‐A, ACHC‐sensitive GABA transporter; GAT‐B, β‐alanine‐sensitive GABA transporter; GLY‐1 and GLYT‐1, glycine transporters; PROT‐1, proline transporter; BGT‐1, betaine transporter.. Transporters for the major amino acid neurotransmitters glutamate, GABA, and glycine are found in both neurons and glial cells. Recent work has resulted in the identification of cDNAs encoding several amino acid neurotransmitter transport proteins, all of which belong to the Na+‐and Cl−‐dependent transporter gene family. The diversity of this family suggests a degree of transporter heterogeneity that is greater than that indicated by biochemical and pharmacological studies. (shrink)

A tight control of intracellular [Ca2+\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{2+}$$\end{document}] is essential for the survival and normal function of cells. In this study we investigate key mechanistic steps by which calcium is regulated and calcium oscillations could occur using in silico modeling of membrane transporters. To do so we give a deterministic description of intracellular Ca2+\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{2+}$$\end{document} dynamics using nonlinear dynamics in order to understand Ca2+\documentclass[12pt]{minimal} \usepackage{amsmath} (...) \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{2+}$$\end{document} signaling. We first present the ordinary differential equations system for cell calcium kinetics and make a preliminary work on Sobol indices. We then describe and analyze complex transporters action. Besides, we analyze the whole system. We finally perform numerical simulations and compare our results to real data. (shrink)

Polypeptide growth factors (mitogens) which stimulate proliferation of fibroblasts and epithelial cells also rapidly activate transmembrane ion transport systems. The mitogen‐induced Na+ influx is due to the activation of a Na+/H+ antiport. Recent methodological developments allow, for the first time, precise measurements of the factors that control activation of the Na+/H+ antiport by these agents, and provide the tools needed to assess the physiological significance of this exchange mechanism.

Recent findings in several organ systems show that cytoneme‐mediated signaling transports signaling proteins along cellular extensions and targets cell‐to‐cell exchanges to synaptic contacts. This mechanism of paracrine signaling may be a general one that is used by many (or all) cell types in many (or all) organs. We briefly review these findings in this perspective. We also describe the properties of several signaling systems that have previously been interpreted to support a passive diffusion mechanism of signaling protein dispersion, but can (...) now be understood in the context of the cytoneme mechanism.Also watch the Video Abstract. (shrink)

Endothelial cells in culture have, in the past, been a valuable but capricious tool to test hypotheses on the role of components of the blood vessel wall in such functions as blood pressure homeostasis, hemostasis, permeability, transport of macromolecules and the processing of circulating biologically active substances. Now techniques are becoming available for raising long‐term, large‐scale cultures that can be maintained reproducibly and without loss of phenotypic characteristics. The outlook for establishing endothelial cell factories invites speculation on some (...) far‐reaching possibilities, such as endothelial cell banks that could be used for seeding autogenous cells on vascular prostheses, artificial kidney tubing, heart valves, or corneas, or for virus production, or for synthesis by endothelial cells of products at present beyond the reach of bacterial cells. (shrink)

Chromosome segregation requires the ordered separation of the newly replicated chromosomes between the two daughter cells. In most cells, this requires nuclear envelope (NE) disassembly during mitotic entry and its reformation at mitotic exit. Nuclear envelope breakdown (NEB) results in the mixture of two cellular compartments. This process is controlled through phosphorylation of multiple targets by cyclin‐dependent kinase 1 (Cdk1)‐cyclin B complexes as well as other mitotic enzymes. Experimental evidence also suggests that nucleo‐cytoplasmic transport of critical cell (...) cycle regulators such as Cdk1‐cyclin B complexes or Greatwall, a kinase responsible for the inactivation of PP2A phosphatases, plays a major role in maintaining the boost of mitotic phosphorylation thus preventing the potential mitotic collapse derived from NEB. These data suggest the relevance of nucleo‐cytoplasmic transport not only to communicate cytoplasmic and nuclear compartments during interphase, but also to prepare cells for the mixture of these two compartments during mitosis. (shrink)

The hemolysin toxin (HlyA) is secreted across both the cytoplasmic and outer membranes of pathogenic Escherichia coli and forms membrane pores in cells of the host immune system, causing cell dysfunction and death. The processes underlying the interaction of HlyA with the bacterial and mammalian cell membranes are remarkable. Secretion of HlyA occurs without a periplasmic intermediate and is directed by an uncleaved C‐terminal targetting signal and the HlyB and HlyD translocator proteins, the former being a member of a (...) transporter superfamily central to import and export of a wide range of substrates by prokaryotic and eukaryotic cells. The separate process by which HlyA is targetted to mammalian cell membranes is dependent upon fatty acylation of a non‐toxic precursor, proHlyA. This is achieved by a novel mechanism directed by the activator protein HlyC, which binds to an internal proHlyA recognition sequence and provides specificity for the transfer of fatty acid from cellular acyl carrier protein. (shrink)

Endosomes shuttle select cargoes between cellular compartments and, in doing so, maintain intracellular homeostasis and enable interactions with the extracellular space. Directionality of endosomal transport critically impinges on cargo fate, as retrograde (microtubule minus‐end directed) traffic delivers vesicle contents to the lysosome for proteolysis, while the opposing anterograde (plus‐end directed) movement promotes recycling and secretion. Intriguingly, the endoplasmic reticulum (ER) is emerging as a key player in spatiotemporal control of late endosome and lysosome transport, through the establishment of (...) physical contacts with these organelles. Earlier studies have described how minus‐end‐directed motor proteins become discharged from vesicles engaged at such contact sites. Now, Raiborg et al. implicate ER‐mediated interactions, induced by protrudin, in loading plus‐end‐directed motor kinesin‐1 onto endosomes, thereby stimulating their transport toward the cell's periphery. In this review, we recast the prevailing concepts on bidirectional late endosome transport and discuss the emerging paradigm of inter‐compartmental regulation from the ER‐endosome interface viewpoint. (shrink)

In general terms there are only three primary energy sources: fossil fuels, renewable energy, and nuclear fission. For fueling road transportation, there has been much speculation about the use of hydrogen as an energy carrier, which would usher in the “hydrogen economy.” A parallel situation would use a simple battery to store electricity directly in order to power vehicles. The efficiency of these two different approaches has been compared and shows that the hydrogen and fuel cell system would consume nearly (...) three times the primary energy required by a battery storage system. Successful introduction into the marketplace of the plug-in hybrid vehicle would eliminate the need for road vehicles to use petroleum fuels, at least for the majority of miles traveled. If electricity were to be generated primarily from sustainable primary energy sources, then road transportation would also become sustainable, resulting in an “electricity economy” rather than a “hydrogen economy.”. (shrink)

This paper presents an integrated model describing the control of Saccharomyces cerevisiae yeast cells bioenergetics. This model describes the oxidative and respirofermentative metabolism. The model assumes that the mitochondria of the Saccharomyces cerevisiae cells are charged with NADH during the tricarboxylic acid cycle, and NADH is discharged from mitochondria later in the electron transport system. Selected effects observed in the Saccharomyces cerevisiae eucaryotic cells, including the Pasteur's and Crabtree effects, are also modeled.

The cellular machinery responsible for conveying proteins between the endoplasmic reticulum and the Golgi is being investigated using genetics and biochemistry. A role for vesicles in mediating protein traffic between the ER and the Golgi has been established by characterizing yeast mutants defective in this process, and by using recently developed cell‐free assays that measure ER to Golgi transport. These tools have also allowed the identification of several proteins crucial to intracellular protein trafficking. The characterization and possible functions of (...) several GTP‐binding proteins, peripheral membrane proteins, and an integral membrane protein during ER to Golgi transport are discussed here. (shrink)

Cells can change their function by rapidly modulating the levels of certain proteins at the plasma membrane. This rapid modulation is achieved by using a specialised trafficking process called constitutive cycling. The constitutive cycling of a variety of transmembrane proteins such as receptors, channels and transporters has recently been directly demonstrated in a wide range of cell types. This regulation is thought to underlie important biological phenomena such as learning and memory, gastric acid secretion and water and blood glucose (...) homeostasis. This review discusses the molecular mechanisms of constitutive cycling, its regulation by extracellular agents such as hormones and its misregulation in disease states. BioEssays 25:39–46, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

As targeted proteins that move within the cell, the steroid receptors have become very useful probes for understanding the linked phenomena of protein folding and transport. From the study of steroid receptor‐associated proteins it has become clear over the past two years that these receptors are bound to a multiprotein complex containing at least two heat shock proteins, hsp90 and hsp56. Attachment of receptors to this complex in a cell‐free system appears to require the protein unfolding/folding activity of a (...) third heat shock protein, hsp70. Like the oncogenic tyrosine kinase pp60src, steroid receptors bind to this complex of chaperone proteins at the time of their translation. Binding of the receptor to the hsp90 component of the system occurs through the hormone binding domain and is under strict hormonal control. The hormone binding domain of the receptor acts as a transferable regulatory unit that confers both tight hormonal control and hsp90 binding onto chimaeric proteins. The model of folding and transport being developed for steroid receptors leads to some general suggestions regarding the folding and transport of targeted proteins in the cell. (shrink)