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Int. J. Mol. Sci., Volume 10, Issue 3 (March 2009), Pages 724-1418

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Editorial

Jump to: Research, Review

Open AccessEditorial Protein Dynamics: From Molecules, to Interactions, to Biology
Int. J. Mol. Sci. 2009, 10(3), 1360-1368; doi:10.3390/ijms10031360
Received: 19 February 2009 / Revised: 13 March 2009 / Accepted: 17 March 2009 / Published: 20 March 2009
PDF Full-text (164 KB) | HTML Full-text | XML Full-text
Abstract
Proteins have a remarkably rich diversity of dynamical behaviors, and the articles in this issue of the International Journal of Molecular Sciences are a testament to that fact. From the picosecond motions of single sidechains probed by NMR or fluorescence spectroscopy, to aggregation
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Proteins have a remarkably rich diversity of dynamical behaviors, and the articles in this issue of the International Journal of Molecular Sciences are a testament to that fact. From the picosecond motions of single sidechains probed by NMR or fluorescence spectroscopy, to aggregation processes at interfaces that take months, all time scales play a role. Proteins are functional molecules, so by their nature they always interact with their environment. This environment includes water, other biomolecules, or larger cellular structures. In a sense, it also includes the protein molecule itself: proteins are large enough to fold and interact with themselves. These interactions have been honed by evolution to produce behaviors completely different from those of random polymers. Full article
(This article belongs to the Special Issue Protein Folding 2009)

Research

Jump to: Editorial, Review

Open AccessArticle Formation versus Hydrolysis of the Peptide Bond from a Quantum-mechanical Viewpoint: The Role of Mineral Surfaces and Implications for the Origin of Life
Int. J. Mol. Sci. 2009, 10(3), 746-760; doi:10.3390/ijms10030746
Received: 16 January 2009 / Revised: 16 February 2009 / Accepted: 23 February 2009 / Published: 26 February 2009
Cited by 7 | PDF Full-text (651 KB) | HTML Full-text | XML Full-text
Abstract
The condensation (polymerization by water elimination) of molecular building blocks to yield the first active biopolymers (e.g. of amino acids to form peptides) during primitive Earth is an intriguing question that nowadays still remains open since these processes are thermodynamically disfavoured in
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The condensation (polymerization by water elimination) of molecular building blocks to yield the first active biopolymers (e.g. of amino acids to form peptides) during primitive Earth is an intriguing question that nowadays still remains open since these processes are thermodynamically disfavoured in highly dilute water solutions. In the present contribution, formation and hydrolysis of glycine oligopeptides occurring on a cluster model of sanidine feldspar (001) surface have been simulated by quantum mechanical methods. Results indicate that the catalytic interplay between Lewis and Brønsted sites both present at the sanidine surface, in cooperation with the London forces acting between the biomolecules and the inorganic surface, plays a crucial role to: i) favour the condensation of glycine to yield oligopeptides as reaction products; ii) inhibit the hydrolysis of the newly formed oligopeptides. Both facts suggest that mineral surfaces may have helped in catalyzing, stabilizing and protecting from hydration the oligopeptides formed in the prebiotic era. Full article
(This article belongs to the Special Issue Origin of Life)
Open AccessArticle Ordering and Reverse Ordering Mechanisms of Triblock Copolymers in the Presence of Solvent
Int. J. Mol. Sci. 2009, 10(3), 805-816; doi:10.3390/ijms10030805
Received: 21 January 2009 / Revised: 24 February 2009 / Accepted: 24 February 2009 / Published: 27 February 2009
Cited by 1 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text
Abstract
Self-consistent field theory is used to study the self-assembly of a triblock copolymer melt. Two different external factors (temperature and solvent) are shown to affect the self-assembly. Either one or two-step self-assembly can be found as a function of temperature in the case
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Self-consistent field theory is used to study the self-assembly of a triblock copolymer melt. Two different external factors (temperature and solvent) are shown to affect the self-assembly. Either one or two-step self-assembly can be found as a function of temperature in the case of a neat triblock melt, or as a function of increasing solvent content (for non-selective solvents) in the case of a triblock-solvent mixture. For selective solvents, it is shown that increasing the solvent content leads to more complicated self-assembly mechanisms, including a reversed transition where order is found to increase instead of decreasing as expected, and re-entrant behavior where order is found to increase at first, and then decrease to a previous state of disorder. Full article
(This article belongs to the Special Issue Molecular Self-Assembly)
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Open AccessArticle Chaperonin Structure - The Large Multi-Subunit Protein Complex
Int. J. Mol. Sci. 2009, 10(3), 844-861; doi:10.3390/ijms10030844
Received: 9 February 2009 / Revised: 23 February 2009 / Accepted: 26 February 2009 / Published: 2 March 2009
Cited by 4 | PDF Full-text (544 KB) | HTML Full-text | XML Full-text
Abstract
The multi sub-unit protein structure representing the chaperonins group is analyzed with respect to its hydrophobicity distribution. The proteins of this group assist protein folding supported by ATP. The specific axial symmetry GroEL structure (two rings of seven units stacked back to back
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The multi sub-unit protein structure representing the chaperonins group is analyzed with respect to its hydrophobicity distribution. The proteins of this group assist protein folding supported by ATP. The specific axial symmetry GroEL structure (two rings of seven units stacked back to back - 524 aa each) and the GroES (single ring of seven units - 97 aa each) polypeptide chains are analyzed using the hydrophobicity distribution expressed as excess/deficiency all over the molecule to search for structure-to-function relationships. The empirically observed distribution of hydrophobic residues is confronted with the theoretical one representing the idealized hydrophobic core with hydrophilic residues exposure on the surface. The observed discrepancy between these two distributions seems to be aim-oriented, determining the structure-to-function relation. The hydrophobic force field structure generated by the chaperonin capsule is presented. Its possible influence on substrate folding is suggested. Full article
(This article belongs to the Special Issue Protein Folding 2009)
Open AccessArticle Grunwald-Winstein Analysis - Isopropyl Chloroformate Solvolysis Revisited
Int. J. Mol. Sci. 2009, 10(3), 862-879; doi:10.3390/ijms10030862
Received: 9 February 2009 / Revised: 20 February 2009 / Accepted: 27 February 2009 / Published: 2 March 2009
Cited by 18 | PDF Full-text (212 KB) | HTML Full-text | XML Full-text
Abstract
Specific rates of solvolysis at 25 °C for isopropyl chloroformate (1) in 24 solvents of widely varying nucleophilicity and ionizing power, plus literature values for studies in water and formic acid, are reported. Previously published solvolytic rate constants at 40.0 °C are supplemented
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Specific rates of solvolysis at 25 °C for isopropyl chloroformate (1) in 24 solvents of widely varying nucleophilicity and ionizing power, plus literature values for studies in water and formic acid, are reported. Previously published solvolytic rate constants at 40.0 °C are supplemented with two additional values in the highly ionizing fluoroalcohols. These rates are now are analyzed using the one and two-term Grunwald-Winstein Equations. In the more ionizing solvents including ten fluoroalcohols negligible sensitivities towards changes in solvent nucleophilicity (l) and very low sensitivities towards changes in solvent ionizing power (m) values are obtained, evocative to those previously observed for 1-adamantyl and 2-adamantyl chloroformates 2 and 3. These observations are rationalized in terms of a dominant solvolysis-decomposition with loss of the CO2 molecule. In nine of the more nucleophilic pure alchohols and aqueous solutions an association-dissociation mechanism is believed to be operative. Deficiencies in the acid production indicate 2-33% isopropyl chloride formation, with the higher values in less nucleophilic solvents. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle Hypoglycemic Effects of Crude Polysaccharide from Purslane
Int. J. Mol. Sci. 2009, 10(3), 880-888; doi:10.3390/ijms10030880
Received: 1 February 2009 / Revised: 19 February 2009 / Accepted: 23 February 2009 / Published: 2 March 2009
Cited by 34 | PDF Full-text (110 KB) | HTML Full-text | XML Full-text
Abstract
The effects of crude polysaccharide from Purslane (CPP) on body weight (bw), blood glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG) and serum insulin levels were studied in diabetes mellitus mice. CPP treatment (200, 400 mg/kg bw) for 28 days resulted
[...] Read more.
The effects of crude polysaccharide from Purslane (CPP) on body weight (bw), blood glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG) and serum insulin levels were studied in diabetes mellitus mice. CPP treatment (200, 400 mg/kg bw) for 28 days resulted in a significant decrease in the concentrations of fasting blood glucose (FBG), TC and TG. Furthermore, CPP significantly increased the concentration of HDL-c, body weight and serum insulin level in the mice. In addition, according to acute toxicity studies and single cell gel electrophoresis analysis, CPP did not produce any physical or behavioral signs of toxicity. More significantly, our data demonstrated CPP exhibited the best effects at the dose of 400 mg/kg bw. The above results suggest that CPP can control blood glucose and modulate the metabolism of glucose and blood lipids in diabetes mellitus mice, so we conclude that CPP should be evaluated as a candidate for future studies on diabetes mellitus. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Corrrelation of the Specific Rates of Solvolysis of Ethyl Fluoroformate Using the Extended Grunwald-Winstein Equation
Int. J. Mol. Sci. 2009, 10(3), 929-941; doi:10.3390/ijms10030929
Received: 15 February 2009 / Revised: 27 February 2009 / Published: 2 March 2009
Cited by 5 | PDF Full-text (196 KB) | HTML Full-text | XML Full-text
Abstract
The specific rates of solvolysis of ethyl fluoroformate have been measured at 24.2 °C in 21 pure and binary solvents. These give a satisfactory correlation over the full range of solvents when the extended Grunwald-Winstein equation is applied. The sensitivities to changes in
[...] Read more.
The specific rates of solvolysis of ethyl fluoroformate have been measured at 24.2 °C in 21 pure and binary solvents. These give a satisfactory correlation over the full range of solvents when the extended Grunwald-Winstein equation is applied. The sensitivities to changes in the NT solvent nucleophilicity scale and the YCl solvent ionizing power scale, and the kF/kCl values are very similar to those for solvolyses of n-octyl fluoroformate, consistent with the addition step of an addition-elimination pathway being rate-determining. For methanolysis, a solvent deuterium isotope effect of 3.10 is compatible with the incorporation of general-base catalysis into the substitution process. For five representative solvents, studies were made at several temperatures and activation parameters determined. The results are also compared with those reported earlier for ethyl chloroformate and mechanistic conclusions are drawn. Full article
(This article belongs to the Special Issue Grunwald-Winstein Equations – 60 Years & Counting)
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Open AccessArticle The Contribution of the Elastic Reaction is Severely Underestimated in Studies on Myofibril Contraction
Int. J. Mol. Sci. 2009, 10(3), 942-953; doi:10.3390/ijms10030942
Received: 23 January 2009 / Revised: 22 February 2009 / Accepted: 24 February 2009 / Published: 2 March 2009
Cited by 2 | PDF Full-text (122 KB) | HTML Full-text | XML Full-text
Abstract
We have considered the Huxley-Simmons manoeuvre. On the assumption that the quick release is an elastic process and on the basis of the isometric tension and of the stiffness of the muscle fibre we calculated that the spontaneous release of the fibre requires
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We have considered the Huxley-Simmons manoeuvre. On the assumption that the quick release is an elastic process and on the basis of the isometric tension and of the stiffness of the muscle fibre we calculated that the spontaneous release of the fibre requires ~43 μs, which is much faster than the observed release, ~180 μs. We concluded that the observed quick release is a guided process. After proper selection of the mass and of the stiffness of the system we mimicked the early recovery and noticed that most of the energy required to accomplish the early recovery is supplied by the kinetic energy accumulated during the course of the quick release. We computed that the frequency of the working strokes in the half sarcomere was between 4×106 and 40×106 s-1. This is not to say that the ATPase rate constants are accumulative but only that the overall frequency of the working strokes in the half saromere is many orders of magnitude faster than the average ATPase rate constant. With this frequency no part of the Huxley-Simmons manoeuvre, quick release included, escapes the control of the working stroke. This means also that there is no reason to take the early recovery as an indication of the length of the working stroke. Full article
Open AccessArticle Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter
Int. J. Mol. Sci. 2009, 10(3), 954-963; doi:10.3390/ijms10030954
Received: 10 February 2009 / Revised: 23 February 2009 / Accepted: 25 February 2009 / Published: 5 March 2009
Cited by 22 | PDF Full-text (234 KB) | HTML Full-text | XML Full-text
Abstract
Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly
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Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of β-arrestin2 was proven by overexpression or knockdown of its homology β-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting β-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Kinetics of Chromium(III) Transport Through a Liquid Membrane Containing DNNSA as a Carrier
Int. J. Mol. Sci. 2009, 10(3), 964-975; doi:10.3390/ijms10030964
Received: 5 January 2009 / Revised: 4 March 2009 / Accepted: 6 March 2009 / Published: 9 March 2009
Cited by 9 | PDF Full-text (270 KB) | HTML Full-text | XML Full-text
Abstract
Kinetics of Cr(III) ions transport through a bulk liquid membrane containing dinonylnaphthalenesulfonic acid (DNNSA) as a carrier, flowing over aqueous phases, has been examined. Special attention has been paid to the effect of the membrane’s velocity flow on the chromium concentration decrease in
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Kinetics of Cr(III) ions transport through a bulk liquid membrane containing dinonylnaphthalenesulfonic acid (DNNSA) as a carrier, flowing over aqueous phases, has been examined. Special attention has been paid to the effect of the membrane’s velocity flow on the chromium concentration decrease in a feed phase. For the description of relationships of chromium(III) concentration in particular phases with the time, a model based on the assumption of consecutive first-order reactions was proposed. Satisfactory compatibility of experiments and model results have been obtained both for the membrane flow velocities below 0.0034 m·s-1 when the interfaces begin to fluctuate slightly and for low initial Cr(III) concentration in the feed phase. Full article
(This article belongs to the Section Green Chemistry)
Open AccessArticle Molecular Pathology of Human Prion Diseases
Int. J. Mol. Sci. 2009, 10(3), 976-999; doi:10.3390/ijms10030976
Received: 2 February 2009 / Revised: 27 February 2009 / Accepted: 4 March 2009 / Published: 9 March 2009
Cited by 35 | PDF Full-text (410 KB) | HTML Full-text | XML Full-text
Abstract
Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP) to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms
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Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP) to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, abundant disease-associated PrP together with tissue pathology characterizes prion diseases and associates with transmissibility. Prion diseases have different etiological background with distinct pathogenesis and phenotype. Mutations of the prion protein gene are associated with genetic forms. The codon 129 polymorphism in combination with the Western blot pattern of PrP after proteinase K digestion serves as a basis for molecular subtyping of sporadic Creutzfeldt-Jakob disease. Tissue damage may result from several parallel, interacting or subsequent pathways that involve cellular systems associated with synapses, protein processing, oxidative stress, autophagy, and apoptosis. Full article
(This article belongs to the Special Issue Advances in Molecular Neuropathology)
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Open AccessArticle Probing the Nanosecond Dynamics of a Designed Three-Stranded Beta-Sheet with a Massively Parallel Molecular Dynamics Simulation
Int. J. Mol. Sci. 2009, 10(3), 1013-1030; doi:10.3390/ijms10031013
Received: 15 January 2009 / Revised: 4 March 2009 / Accepted: 9 March 2009 / Published: 10 March 2009
Cited by 3 | PDF Full-text (1699 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recently a temperature-jump FTIR study of a designed three-stranded sheet showing a fast relaxation time of ~140 ± 20 ns was published. We performed massively parallel molecular dynamics simulations in explicit solvent to probe the structural events involved in this relaxation. While our
[...] Read more.
Recently a temperature-jump FTIR study of a designed three-stranded sheet showing a fast relaxation time of ~140 ± 20 ns was published. We performed massively parallel molecular dynamics simulations in explicit solvent to probe the structural events involved in this relaxation. While our simulations produce similar relaxation rates, the structural ensemble is broad. We observe the formation of turn structure, but only very weak interaction in the strand regions, which is consistent with the lack of strong backbone-backbone NOEs in previous structural NMR studies. These results suggest that either DPDP-II folds at time scales longer than 240 ns, or that DPDP-II is not a well-defined three-stranded β-sheet. This work also provides an opportunity to compare the performance of several popular forcefield models against one another. Full article
(This article belongs to the Special Issue Protein Folding 2009)
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Open AccessArticle Quantitative Prediction of Solvation Free Energy in Octanol of Organic Compounds
Int. J. Mol. Sci. 2009, 10(3), 1031-1044; doi:10.3390/i10031031
Received: 9 February 2009 / Revised: 5 March 2009 / Accepted: 9 March 2009 / Published: 11 March 2009
Cited by 2 | PDF Full-text (67 KB) | HTML Full-text | XML Full-text
Abstract
The free energy of solvation, ΔGS0 , in octanol of organic compunds is quantitatively predicted from the molecular structure. The model, involving only three molecular descriptors, is obtained by multiple linear regression analysis from a data set of 147 compounds
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The free energy of solvation, ΔGS0 , in octanol of organic compunds is quantitatively predicted from the molecular structure. The model, involving only three molecular descriptors, is obtained by multiple linear regression analysis from a data set of 147 compounds containing diverse organic functions, namely, halogenated and non-halogenated alkanes, alkenes, alkynes, aromatics, alcohols, aldehydes, ketones, amines, ethers and esters; covering a ΔGS0 range from about –50 to 0 kJ·mol-1. The model predicts the free energy of solvation with a squared correlation coefficient of 0.93 and a standard deviation, 2.4 kJ·mol-1, just marginally larger than the generally accepted value of experimental uncertainty. The involved molecular descriptors have definite physical meaning corresponding to the different intermolecular interactions occurring in the bulk liquid phase. The model is validated with an external set of 36 compounds not included in the training set. Full article
(This article belongs to the Special Issue Recent Advances in QSAR/QSPR Theory)
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Open AccessArticle Dietary Protection Against Free Radicals: A Case for Multiple Testing to Establish Structure-activity Relationships for Antioxidant Potential of Anthocyanic Plant Species
Int. J. Mol. Sci. 2009, 10(3), 1081-1103; doi:10.3390/ijms10031081
Received: 2 December 2008 / Revised: 27 January 2009 / Accepted: 3 March 2009 / Published: 11 March 2009
Cited by 21 | PDF Full-text (169 KB) | HTML Full-text | XML Full-text
Abstract
DNA damage by reactive species is associated with susceptibility to chronic human degenerative disorders. Anthocyanins are naturally occurring antioxidants, that may prevent or reverse such damage. There is considerable interest in anthocyanic food plants as good dietary sources, with the potential for reducing
[...] Read more.
DNA damage by reactive species is associated with susceptibility to chronic human degenerative disorders. Anthocyanins are naturally occurring antioxidants, that may prevent or reverse such damage. There is considerable interest in anthocyanic food plants as good dietary sources, with the potential for reducing susceptibility to chronic disease. While structure-activity relationships have provided guidelines on molecular structure in relation to free hydroxyl- radical scavenging, this may not cover the situation in food plants where the anthocyanins are part of a complex mixture, and may be part of complex structures, including anthocyanic vacuolar inclusions (AVIs). Additionally, new analytical methods have revealed new structures in previously-studied materials. We have compared the antioxidant activities of extracts from six anthocyanin-rich edible plants (red cabbage, red lettuce, blueberries, pansies, purple sweetpotato skin, purple sweetpotato flesh and Maori potato flesh) using three chemical assays (DPPH, TRAP and ORAC), and the in vitro Comet assay. Extracts from the flowering plant, lisianthus, were used for comparison. The extracts showed differential effects in the chemical assays, suggesting that closely related structures have different affinities to scavenge different reactive species. Integration of anthocyanins to an AVI led to more sustained radical scavenging activity as compared with the free anthocyanin. All but the red lettuce extract could reduce endogenous DNA damage in HT-29 colon cancer cells. However, while extracts from purple sweetpotato skin and flesh, Maori potato and pansies, protected cells against subsequent challenge by hydrogen peroxide at 0oC, red cabbage extracts were pro-oxidant, while other extracts had no effect. When the peroxide challenge was at 37oC, all of the extracts appeared pro-oxidant. Maori potato extract, consistently the weakest antioxidant in all the chemical assays, was more effective in the Comet assays. These results highlight the dangers of generalising to potential health benefits, based solely on identification of high anthocyanic content in plants, results of a single antioxidant assay and traditional approaches to structure activity relationships. Subsequent studies might usefully consider complex mixtures and a battery of assays. Full article
(This article belongs to the Special Issue Structure-Property/Activity Modeling of Polyphenols)
Open AccessArticle Calcium Ions Regulate K+ Uptake into Brain Mitochondria: The Evidence for a Novel Potassium Channel
Int. J. Mol. Sci. 2009, 10(3), 1104-1120; doi:10.3390/ijms10031104
Received: 18 February 2009 / Revised: 6 March 2009 / Accepted: 10 March 2009 / Published: 12 March 2009
Cited by 40 | PDF Full-text (500 KB) | HTML Full-text | XML Full-text
Abstract
The mitochondrial response to changes of cytosolic calcium concentration has a strong impact on neuronal cell metabolism and viability. We observed that Ca2+ additions to isolated rat brain mitochondria induced in potassium ion containing media a mitochondrial membrane potential depolarization and an
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The mitochondrial response to changes of cytosolic calcium concentration has a strong impact on neuronal cell metabolism and viability. We observed that Ca2+ additions to isolated rat brain mitochondria induced in potassium ion containing media a mitochondrial membrane potential depolarization and an accompanying increase ofmitochondrial respiration. These Ca2+ effects can be blocked by iberiotoxin and charybdotoxin, well known inhibitors of large conductance potassium channel (BKCa channel). Furthermore, NS1619 – a BKCa channel opener – induced potassium ion–specific effects on brain mitochondria similar to those induced by Ca2+. These findings suggest the presence of a calcium-activated, large conductance potassium channel (sensitive to charybdotoxin and NS1619), which was confirmed by reconstitution of the mitochondrial inner membrane into planar lipid bilayers. The conductance of the reconstituted channel was 265 pS under gradient (50/450 mM KCl) conditions. Its reversal potential was equal to 50 mV, which proved that the examined channel was cation-selective. We also observed immunoreactivity of anti-b4 subunit (of the BKCa channel) antibodies with ~26 kDa proteins of rat brain mitochondria. Immunohistochemical analysis confirmed the predominant occurrence of b4 subunit in neuronal mitochondria. We hypothesize that the mitochondrial BKCa channel represents a calcium sensor, which can contribute to neuronal signal transduction and survival. Full article
(This article belongs to the Special Issue Molecular System Bioenergetics)
Open AccessArticle Folding of Trp-cage Mini Protein Using Temperature and Biasing Potential Replica—Exchange Molecular Dynamics Simulations
Int. J. Mol. Sci. 2009, 10(3), 1121-1137; doi:10.3390/ijms10031121
Received: 2 February 2009 / Revised: 5 March 2009 / Accepted: 9 March 2009 / Published: 12 March 2009
Cited by 13 | PDF Full-text (553 KB) | HTML Full-text | XML Full-text
Abstract
The folding process of the 20 residue Trp-cage mini-protein was investigated using standard temperature replica exchange molecular dynamics (T-RexMD) simulation and a biasing potential RexMD (BP-RexMD) method. In contrast to several conventional molecular dynamics simulations, both RexMD methods sampled conformations close to the
[...] Read more.
The folding process of the 20 residue Trp-cage mini-protein was investigated using standard temperature replica exchange molecular dynamics (T-RexMD) simulation and a biasing potential RexMD (BP-RexMD) method. In contrast to several conventional molecular dynamics simulations, both RexMD methods sampled conformations close to the native structure after 10-20 ns simulation time as the dominant conformational states. In contrast, to T-RexMD involving 16 replicas the BP-RexMD method achieved very similar sampling results with only five replicas. The result indicates that the BP-RexMD method is well suited to study folding processes of proteins at a significantly smaller computational cost, compared to T-RexMD. Both RexMD methods sampled not only similar final states but also agreed on the sampling of intermediate conformations during Trp-cage folding. The analysis of the sampled potential energy contributions indicated that Trp-cage folding is favored by both van der Waals and to a lesser degree electrostatic contributions. Folding does not introduce any significant sterical strain as reflected by similar energy distributions of bonded energy terms (bond length, bond angle and dihedral angle) of folded and unfolded Trp-cage structures. Full article
(This article belongs to the Special Issue Protein Folding 2009)
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Open AccessArticle Changes in Metallothionein Level in Rat Hepatic Tissue after Administration of Natural Mouldy Wheat
Int. J. Mol. Sci. 2009, 10(3), 1138-1160; doi:10.3390/ijms10031138
Received: 3 January 2009 / Revised: 28 February 2009 / Accepted: 9 March 2009 / Published: 12 March 2009
Cited by 14 | PDF Full-text (644 KB) | HTML Full-text | XML Full-text
Abstract
Mycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. This work was aimed at investigation of influence of mouldy wheat contaminated by pathogenic fungi producing mycotoxins on metallothionein levels in hepatic tissue
[...] Read more.
Mycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. This work was aimed at investigation of influence of mouldy wheat contaminated by pathogenic fungi producing mycotoxins on metallothionein levels in hepatic tissue of rats. The rats were administrating feed mixtures with different contents of vitamins or naturally mouldy wheat for 28 days. It was found that the wheat contained deoxynivalenol (80 ± 5 µg per kg of mouldy wheat), zearalenone (56 ± 3 µg/kg), T2-toxin (20 ± 2 µg/kg) and aflatoxins as a sum of B1, B2, G1 and G2 (3.9 ± 0.2 µg/kg). Rats were fed diets containing 0, 33, 66 and 100% naturally moulded wheat. Control group 0, 33, 66 and 100% contained vitamins according to Nutrient Requirements of Rats (NRC). Other four groups (control group with vitamins, vit33, vit66 and vit100%) were fed on the same levels of mouldy wheat, also vitamins at levels 100% higher than the previous mixtures. We determined weight, feed conversion and performed dissection to observe pathological processes. Changes between control group and experimental groups exposed to influence of mouldy wheat and experimental groups supplemented by higher concentration of vitamins and mouldy wheat were not observed. Livers were sampled and did not demonstrate significant changes in morphology compared to control either. In the following experiments the levels of metallothionein as a marker of oxidative stress was determined. We observed a quite surprising trend in metallothionein levels in animals supplemented with increased concentration of vitamins. Its level enhanced with increasing content of mouldy wheat. It was possible to determine a statistically significant decline (p<0.05) between control group and groups of animals fed with 33, 66 and 100% mouldy wheat. It is likely that some mycotoxins presented in mouldy wheat are able to block the mechanism of metallothionein synthesis. Full article
Open AccessArticle Quantum-SAR Extension of the Spectral-SAR Algorithm. Application to Polyphenolic Anticancer Bioactivity
Int. J. Mol. Sci. 2009, 10(3), 1193-1214; doi:10.3390/ijms10031193
Received: 18 January 2009 / Revised: 9 March 2009 / Accepted: 11 March 2009 / Published: 16 March 2009
Cited by 32 | PDF Full-text (295 KB) | HTML Full-text | XML Full-text
Abstract
Aiming to assess the role of individual molecular structures in the molecular mechanism of ligand-receptor interaction correlation analysis, the recent Spectral-SAR approach is employed to introduce the Quantum-SAR (QuaSAR) “wave” and “conversion factor” in terms of difference between inter-endpoint inter-molecular activities for a
[...] Read more.
Aiming to assess the role of individual molecular structures in the molecular mechanism of ligand-receptor interaction correlation analysis, the recent Spectral-SAR approach is employed to introduce the Quantum-SAR (QuaSAR) “wave” and “conversion factor” in terms of difference between inter-endpoint inter-molecular activities for a given set of compounds; this may account for inter-conversion (metabolization) of molecular (concentration) effects while indicating the structural (quantum) based influential/detrimental role on bio-/eco- effect in a causal manner rather than by simple inspection of measured values; the introduced QuaSAR method is then illustrated for a study of the activity of a series of flavonoids on breast cancer resistance protein. Full article
(This article belongs to the Special Issue Recent Advances in QSAR/QSPR Theory)
Open AccessArticle Ultra Low-Dose Radiation: Stress Responses and Impacts Using Rice as a Grass Model
Int. J. Mol. Sci. 2009, 10(3), 1215-1225; doi:10.3390/ijms10031215
Received: 5 February 2009 / Revised: 11 March 2009 / Accepted: 13 March 2009 / Published: 16 March 2009
Cited by 13 | PDF Full-text (358 KB) | HTML Full-text | XML Full-text
Abstract
We report molecular changes in leaves of rice plants (Oryza sativa L. - reference crop plant and grass model) exposed to ultra low-dose ionizing radiation, first using contaminated soil from the exclusion zone around Chernobyl reactor site. Results revealed induction of stress-related
[...] Read more.
We report molecular changes in leaves of rice plants (Oryza sativa L. - reference crop plant and grass model) exposed to ultra low-dose ionizing radiation, first using contaminated soil from the exclusion zone around Chernobyl reactor site. Results revealed induction of stress-related marker genes (Northern blot) and secondary metabolites (LC-MS/MS) in irradiated leaf segments over appropriate control. Second, employing the same in vitro model system, we replicated results of the first experiment using in-house fabricated sources of ultra low-dose gamma (g) rays and selected marker genes by RT-PCR. Results suggest the usefulness of the rice model in studying ultra low-dose radiation response/s. Full article
(This article belongs to the Special Issue Biotic and Abiotic Stress)
Open AccessArticle Dielectric Properties of Binary Solvent Mixtures of Dimethyl Sulfoxide with Water
Int. J. Mol. Sci. 2009, 10(3), 1261-1270; doi:10.3390/ijms10031261
Received: 6 February 2009 / Revised: 8 March 2009 / Accepted: 11 March 2009 / Published: 17 March 2009
Cited by 26 | PDF Full-text (275 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, the dielectric properties of water-dimethylsulfoxide (DMSO) mixtures with different mole ratios have been investigated in the range of 1 GHz to 40 GHz at 298 K by using a molecular dynamics (MD) simulation. Only one dielectric loss peak was observed
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In this paper, the dielectric properties of water-dimethylsulfoxide (DMSO) mixtures with different mole ratios have been investigated in the range of 1 GHz to 40 GHz at 298 K by using a molecular dynamics (MD) simulation. Only one dielectric loss peak was observed in the frequency range and the relaxation in these mixtures can be described by a single relaxation time of the Davidson-Cole. It was observed that within experimental error the dielectric relaxation can be described by the Debye-like model (β ≈ 1, S.M. Puranik, et al. J. Chem. Soc. Faraday Trans.1992, 88, 433 - 435). In general, the results are very consistent with the experimental measurements. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle Explaining Ionic Liquid Water Solubility in Terms of Cation and Anion Hydrophobicity
Int. J. Mol. Sci. 2009, 10(3), 1271-1289; doi:10.3390/ijms10031271
Received: 12 February 2009 / Revised: 11 March 2009 / Accepted: 16 March 2009 / Published: 18 March 2009
Cited by 61 | PDF Full-text (314 KB) | HTML Full-text | XML Full-text
Abstract
The water solubility of salts is ordinarily dictated by lattice energy and ion solvation. However, in the case of low melting salts also known as ionic liquids, lattice energy is immaterial and differences in hydrophobicity largely account for differences in their water solubility.
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The water solubility of salts is ordinarily dictated by lattice energy and ion solvation. However, in the case of low melting salts also known as ionic liquids, lattice energy is immaterial and differences in hydrophobicity largely account for differences in their water solubility. In this contribution, the activity coefficients of ionic liquids in water are split into cation and anion contributions by regression against cation hydrophobicity parameters that are experimentally determined by reversed phase liquid chromatography. In this way, anion hydrophobicity parameters are derived, as well as an equation to estimate water solubilities for cation-anion combinations for which the water solubility has not been measured. Thus, a new pathway to the quantification of aqueous ion solvation is shown, making use of the relative weakness of interactions between ionic liquid ions as compared to their hydrophobicities. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Open AccessArticle Origin of Homochirality in Biosystems
Int. J. Mol. Sci. 2009, 10(3), 1290-1299; doi:10.3390/ijms10031290
Received: 12 January 2009 / Revised: 12 March 2009 / Accepted: 18 March 2009 / Published: 18 March 2009
Cited by 12 | PDF Full-text (187 KB) | HTML Full-text | XML Full-text
Abstract
Experimental data for a series of central and simple molecules in biosystems show that some amino acids and a simple sugar molecule have a chiral discrimination in favor of homochirality. Models for segregation of racemic mixtures of chiral amphiphiles and lipophiles in aqueous
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Experimental data for a series of central and simple molecules in biosystems show that some amino acids and a simple sugar molecule have a chiral discrimination in favor of homochirality. Models for segregation of racemic mixtures of chiral amphiphiles and lipophiles in aqueous solutions show that the amphiphiles with an active isomerization kinetics can perform a spontaneous break of symmetry during the segregation and self-assembly to homochiral matter. Based on this observation it is argued that biomolecules with a sufficiently strong chiral discrimination could be the origin of homochirality in biological systems. Full article
(This article belongs to the Special Issue Origin of Life)
Open AccessArticle AFM and Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) Studies on Formation of Air-Stable Supported Lipid Bilayers
Int. J. Mol. Sci. 2009, 10(3), 1407-1418; doi:10.3390/ijms10031407
Received: 31 January 2009 / Revised: 11 March 2009 / Accepted: 19 March 2009 / Published: 26 March 2009
Cited by 1 | PDF Full-text (402 KB) | HTML Full-text | XML Full-text
Abstract
Supported lipid bilayers (SLBs) were prepared by deposition of unilamellar vesicles on a silicon substrate. Atomic force microscopy (AFM) and a new Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) developed by us were used to trace the dynamic formation of lipid bilayers on the silicon
[...] Read more.
Supported lipid bilayers (SLBs) were prepared by deposition of unilamellar vesicles on a silicon substrate. Atomic force microscopy (AFM) and a new Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) developed by us were used to trace the dynamic formation of lipid bilayers on the silicon surfaces. The evolution from deformation of vesicles to formation of bilayers can be distinguished clearly by AFM imaging. MTR-IR provided high quality infrared spectra of ultrathin lipid bilayers with high sensitivity and high signal to noise ratio (SNR). The structural and orientational changes during vesicle’s fusion were monitored with MTR-IR. MTR-IR shows superiority over other infrared approaches for ultrathin films on standard silicon wafers in view of its economy and high sensitivity. Both MTR-IR and AFM results were consistent with each other and they provided more information for understanding the self-assembling procedure of SLBs. Full article
(This article belongs to the Special Issue Molecular Self-Assembly)
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Open AccessReview Molecular Pathology of Lewy Body Diseases
Int. J. Mol. Sci. 2009, 10(3), 724-745; doi:10.3390/ijms10030724
Received: 18 December 2008 / Revised: 3 February 2009 / Accepted: 23 February 2009 / Published: 26 February 2009
Cited by 21 | PDF Full-text (115 KB) | HTML Full-text | XML Full-text
Abstract
Lewy body diseases are characterized by the presence of Lewy bodies, alpha-synuclein(AS)-positive inclusions in the brain. Since their main component is conformationally modified AS, aggregation of the latter is thought to be a key pathogenic event in these diseases. The analysis of inclusion
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Lewy body diseases are characterized by the presence of Lewy bodies, alpha-synuclein(AS)-positive inclusions in the brain. Since their main component is conformationally modified AS, aggregation of the latter is thought to be a key pathogenic event in these diseases. The analysis of inclusion body constituents gives additional information about pathways also involved in the pathology of synucleinopathies. Widespread mitochondrial dysfunction is very closely related to disease development. The impairment of protein degradation pathways, including both the ubiquitin-proteasome system and the autophagy-lysosomepathway also play an important role during the development of Lewy body diseases. Finally, differential expression changes of isoforms corresponding to genes primarily involved in Lewy body formation point to alternative splicing as another important mechanism in the development of Parkinson’s disease, as well as dementia with Lewy bodies. The present paper attempts to give an overview of recent molecular findings related to the pathogenesis of Lewy body diseases. Full article
(This article belongs to the Special Issue Advances in Molecular Neuropathology)
Open AccessReview An Algorithm for Emulsion Stability Simulations: Account of Flocculation, Coalescence, Surfactant Adsorption and the Process of Ostwald Ripening
Int. J. Mol. Sci. 2009, 10(3), 761-804; doi:10.3390/ijms10030761
Received: 18 November 2008 / Revised: 1 January 2009 / Accepted: 13 January 2009 / Published: 26 February 2009
Cited by 19 | PDF Full-text (472 KB) | HTML Full-text | XML Full-text
Abstract
The first algorithm for Emulsion Stability Simulations (ESS) was presented at the V Conferencia Iberoamericana sobre Equilibrio de Fases y Diseño de Procesos [Luis, J.; García-Sucre, M.; Urbina-Villalba, G. Brownian Dynamics Simulation of Emulsion Stability In: Equifase 99. Libro de Actas, 1
[...] Read more.
The first algorithm for Emulsion Stability Simulations (ESS) was presented at the V Conferencia Iberoamericana sobre Equilibrio de Fases y Diseño de Procesos [Luis, J.; García-Sucre, M.; Urbina-Villalba, G. Brownian Dynamics Simulation of Emulsion Stability In: Equifase 99. Libro de Actas, 1st Ed., Tojo J., Arce, A., Eds.; Solucion’s: Vigo, Spain, 1999; Volume 2, pp. 364-369]. The former version of the program consisted on a minor modification of the Brownian Dynamics algorithm to account for the coalescence of drops. The present version of the program contains elaborate routines for time-dependent surfactant adsorption, average diffusion constants, and Ostwald ripening. Full article
(This article belongs to the Special Issue Algorithms and Molecular Sciences)
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Open AccessReview The Role of Disordered Ribosomal Protein Extensions in the Early Steps of Eubacterial 50 S Ribosomal Subunit Assembly
Int. J. Mol. Sci. 2009, 10(3), 817-834; doi:10.3390/ijms10030817
Received: 5 February 2009 / Revised: 23 February 2009 / Accepted: 24 February 2009 / Published: 2 March 2009
Cited by 20 | PDF Full-text (6304 KB) | HTML Full-text | XML Full-text
Abstract
Although during the past decade research has shown the functional importance of disorder in proteins, many of the structural and dynamics properties of intrinsically unstructured proteins (IUPs) remain to be elucidated. This review is focused on the role of the extensions of the
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Although during the past decade research has shown the functional importance of disorder in proteins, many of the structural and dynamics properties of intrinsically unstructured proteins (IUPs) remain to be elucidated. This review is focused on the role of the extensions of the ribosomal proteins in the early steps of the assembly of the eubacterial 50 S subunit. The recent crystallographic structures of the ribosomal particles have revealed the picture of a complex assembly pathway that condenses the rRNA and the ribosomal proteins into active ribosomes. However, little is know about the molecular mechanisms of this process. It is thought that the long basic r-protein extensions that penetrate deeply into the subunit cores play a key role through disorder-order transitions and/or co-folding mechanisms. A current view is that such structural transitions may facilitate the proper rRNA folding. In this paper, the structures of the proteins L3, L4, L13, L20, L22 and L24 that have been experimentally found to be essential for the first steps of ribosome assembly have been compared. On the basis of their structural and dynamics properties, three categories of extensions have been identified. Each of them seems to play a distinct function. Among them, only the coil-helix transition that occurs in a phylogenetically conserved cluster of basic residues of the L20 extension appears to be strictly required for the large subunit assembly in eubacteria. The role of a helix-coil transitions in 23 S RNA folding is discussed in the light of the calcium binding protein calmodulin that shares many structural and dynamics properties with L20. Full article
(This article belongs to the Special Issue Protein Folding 2009)
Open AccessReview Model Protocells from Single-Chain Lipids
Int. J. Mol. Sci. 2009, 10(3), 835-843; doi:10.3390/ijms10030835
Received: 6 February 2009 / Revised: 23 February 2009 / Accepted: 26 February 2009 / Published: 2 March 2009
Cited by 12 | PDF Full-text (101 KB) | HTML Full-text | XML Full-text
Abstract
Significant progress has been made in the construction of laboratory models of protocells. Most frequently the developed vesicle systems utilize single-chain lipids rather than the double-chain lipids typically found in biological membranes. Although single-chain lipids yield less robust vesicles, their dynamic characteristics are
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Significant progress has been made in the construction of laboratory models of protocells. Most frequently the developed vesicle systems utilize single-chain lipids rather than the double-chain lipids typically found in biological membranes. Although single-chain lipids yield less robust vesicles, their dynamic characteristics are highly exploitable for protocellular functions. Herein the advantages of using single-chain lipids in the construction of protocells are discussed. Full article
(This article belongs to the Special Issue Origin of Life)
Open AccessReview Insights from Coarse-Grained Gō Models for Protein Folding and Dynamics
Int. J. Mol. Sci. 2009, 10(3), 889-905; doi:10.3390/ijms10030889
Received: 21 January 2009 / Revised: 23 February 2009 / Accepted: 26 February 2009 / Published: 2 March 2009
Cited by 131 | PDF Full-text (470 KB) | HTML Full-text | XML Full-text
Abstract
Exploring the landscape of large scale conformational changes such as protein folding at atomistic detail poses a considerable computational challenge. Coarse-grained representations of the peptide chain have therefore been developed and over the last decade have proved extremely valuable. These include topology-based Gō
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Exploring the landscape of large scale conformational changes such as protein folding at atomistic detail poses a considerable computational challenge. Coarse-grained representations of the peptide chain have therefore been developed and over the last decade have proved extremely valuable. These include topology-based Gō models, which constitute a smooth and funnel-like approximation to the folding landscape. We review the many variations of the Gō model that have been employed to yield insight into folding mechanisms. Their success has been interpreted as a consequence of the dominant role of the native topology in folding. The role of local contact density in determining protein dynamics is also discussed and is used to explain the ability of Gō-like models to capture sequence effects in folding and elucidate conformational transitions. Full article
(This article belongs to the Special Issue Protein Folding 2009)
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Open AccessReview Multiple, but Concerted Cellular Activities of the Human Protein Hap46/BAG-1M and Isoforms
Int. J. Mol. Sci. 2009, 10(3), 906-928; doi:10.3390/ijms10030906
Received: 11 January 2009 / Accepted: 23 February 2009 / Published: 2 March 2009
Cited by 7 | PDF Full-text (939 KB) | HTML Full-text | XML Full-text
Abstract
The closely related human and murine proteins Hap46/BAG-1M and BAG-1, respectively, were discovered more than a decade ago by molecular cloning techniques. These and the larger isoform Hap50/BAG-1L, as well as shorter isoforms, have the ability to interact with a seemingly unlimited array
[...] Read more.
The closely related human and murine proteins Hap46/BAG-1M and BAG-1, respectively, were discovered more than a decade ago by molecular cloning techniques. These and the larger isoform Hap50/BAG-1L, as well as shorter isoforms, have the ability to interact with a seemingly unlimited array of proteins of completely unrelated structures. This problem was partially resolved when it was realized that molecular chaperones of the hsp70 heat shock protein family are major primary association partners, binding being mediated by the carboxy terminal BAG-domain and the ATP-binding domain of hsp70 chaperones. The latter, in turn, can associate with an almost unlimited variety of proteins through their substrate-binding domains, so that ternary complexes may result. The protein folding activity of hsp70 chaperones is affected by interactions with Hap46/BAG-1M or isoforms. However, there also exist several proteins which bind to Hap46/BAG-1M and isoforms independent of hsp70 mediation. Moreover, Hap46/BAG-1M and Hap50/BAG-1L, but not the shorter isoforms, can bind to DNA in a sequence-independent manner by making use of positively charged regions close to their amino terminal ends. This is the molecular basis for their effects on transcription which are of major physiological relevance, as discussed here in terms of a model. The related proteins Hap50/BAG-1L and Hap46/BAG-1M may thus serve as molecular links between such diverse bioactivities as regulation of gene expression and protein quality control. These activities are coordinated and synergize in helping cells to cope with conditions of external stress. Moreover, they recently became markers for the aggressiveness of several cancer types. Full article
(This article belongs to the Special Issue Protein Folding 2009)
Open AccessReview Neuropathology and Therapeutic Intervention in Spinal and Bulbar Muscular Atrophy
Int. J. Mol. Sci. 2009, 10(3), 1000-1012; doi:10.3390/ijms10031000
Received: 26 January 2009 / Revised: 6 March 2009 / Accepted: 9 March 2009 / Published: 10 March 2009
Cited by 3 | PDF Full-text (1515 KB) | HTML Full-text | XML Full-text
Abstract
Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The histopathological finding in SBMA is loss of lower motor neurons in the anterior horn of the spinal
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Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The histopathological finding in SBMA is loss of lower motor neurons in the anterior horn of the spinal cord as well as in the brainstem motor nuclei. Animal studies have revealed that the pathogenesis of SBMA depends on the level of serum testosterone, and that androgen deprivation mitigates neurodegeneration through inhibition of nuclear accumulation of the pathogenic AR. Heat shock proteins, ubiquitin-proteasome system and transcriptional regulation are also potential targets of therapy development for SBMA. Full article
(This article belongs to the Special Issue Advances in Molecular Neuropathology)
Open AccessReview Molecular Pathology of Neuro-AIDS (CNS-HIV)
Int. J. Mol. Sci. 2009, 10(3), 1045-1063; doi:10.3390/ijms10031045
Received: 9 February 2009 / Revised: 5 March 2009 / Accepted: 9 March 2009 / Published: 11 March 2009
Cited by 33 | PDF Full-text (655 KB) | HTML Full-text | XML Full-text
Abstract
The cognitive deficits in patients with HIV profoundly affect the quality of life of people living with this disease and have often been linked to the neuro-inflammatory condition known as HIV encephalitis (HIVE). With the advent of more effective anti-retroviral therapies, HIVE has
[...] Read more.
The cognitive deficits in patients with HIV profoundly affect the quality of life of people living with this disease and have often been linked to the neuro-inflammatory condition known as HIV encephalitis (HIVE). With the advent of more effective anti-retroviral therapies, HIVE has shifted from a sub-acute to a chronic condition. The neurodegenerative process in patients with HIVE is characterized by synaptic and dendritic damage to pyramidal neurons, loss of calbindin-immunoreactive interneurons and myelin loss. The mechanisms leading to neurodegeneration in HIVE might involve a variety of pathways, and several lines of investigation have found that interference with signaling factors mediating neuroprotection might play an important role. These signaling pathways include, among others, the GSK3b, CDK5, ERK, Pyk2, p38 and JNK cascades. Of these, GSK3b has been a primary focus of many previous studies showing that in infected patients, HIV proteins and neurotoxins secreted by immune-activated cells in the brain abnormally activate this pathway, which is otherwise regulated by growth factors such as FGF. Interestingly, modulation of the GSK3b signaling pathway by FGF1 or GSK3b inhibitors (lithium, valproic acid) is protective against HIV neurotoxicity, and several pilot clinical trials have demonstrated cognitive improvements in HIV patients treated with GSK3b inhibitors. In addition to the GSK3b pathway, the CDK5 pathway has recently been implicated as a mediator of neurotoxicity in HIV, and HIV proteins might activate this pathway and subsequently disrupt the diverse processes that CDK5 regulates, including synapse formation and plasticity and neurogenesis. Taken together, the GSK3b and CDK5 signaling pathways are important regulators of neurotoxicity in HIV, and modulation of these factors might have therapeutic potential in the treatment of patients suffering from HIVE. In this context, the subsequent sections will focus on reviewing the involvement of the GSK3b and CDK5 pathways in neurodegeneration in HIV. Full article
(This article belongs to the Special Issue Advances in Molecular Neuropathology)
Open AccessReview Importance of Translational Entropy of Water in Biological Self-Assembly Processes like Protein Folding
Int. J. Mol. Sci. 2009, 10(3), 1064-1080; doi:10.3390/ijms10031064
Received: 26 January 2009 / Revised: 6 March 2009 / Accepted: 10 March 2009 / Published: 11 March 2009
Cited by 42 | PDF Full-text (287 KB) | HTML Full-text | XML Full-text
Abstract
We briefly review our studies on the folding/unfolding mechanisms of proteins. In biological self-assembly processes such as protein folding, the number of accessible translational configurations of water in the system increases greatly, leading to a large gain in the water entropy. The usual
[...] Read more.
We briefly review our studies on the folding/unfolding mechanisms of proteins. In biological self-assembly processes such as protein folding, the number of accessible translational configurations of water in the system increases greatly, leading to a large gain in the water entropy. The usual view looking at only the water in the close vicinity of the protein surface is capable of elucidating neither the large entropic gain upon apoplastocyanin folding, which has recently been found in a novel experimental study, nor the pressure and cold denaturation. With the emphasis on the translational entropy of water, we are presently constructing a reliable method for predicting the native structure of a protein from its amino-acid sequence. Full article
(This article belongs to the Special Issue Protein Folding 2009)
Open AccessReview Philosophical Basis and Some Historical Aspects of Systems Biology: From Hegel to Noble - Applications for Bioenergetic Research
Int. J. Mol. Sci. 2009, 10(3), 1161-1192; doi:10.3390/ijms10031161
Received: 3 February 2009 / Revised: 7 March 2009 / Accepted: 12 March 2009 / Published: 13 March 2009
Cited by 26 | PDF Full-text (1541 KB) | HTML Full-text | XML Full-text
Abstract
We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems
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We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems Biology - defined as the higher level analysis of complex biological systems - was pioneered by Claude Bernard in physiology, Norbert Wiener with the development of cybernetics, and Erwin Schrödinger in his thermodynamic approach to the living. Systems Biology applies methods inspired by cybernetics, network analysis, and non-equilibrium dynamics of open systems. These developments follow very precisely the dialectical principles of development from thesis to antithesis to synthesis discovered by Hegel. Systems Biology opens new perspectives for studies of the integrated processes of energy metabolism in different cells. These integrated systems acquire new, system-level properties due to interaction of cellular components, such as metabolic compartmentation, channeling and functional coupling mechanisms, which are central for regulation of the energy fluxes. State of the art of these studies in the new area of Molecular System Bioenergetics is analyzed. Full article
(This article belongs to the Special Issue Molecular System Bioenergetics)
Open AccessReview Physiological and Pathological Role of Alpha-synuclein in Parkinson’s Disease Through Iron Mediated Oxidative Stress; The Role of a Putative Iron-responsive Element
Int. J. Mol. Sci. 2009, 10(3), 1226-1260; doi:10.3390/ijms10031226
Received: 31 December 2008 / Revised: 3 March 2009 / Accepted: 11 March 2009 / Published: 17 March 2009
Cited by 41 | PDF Full-text (307 KB) | HTML Full-text | XML Full-text
Abstract
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer's disease (AD) and represents a large health burden to society. Genetic and oxidative risk factors have been proposed as possible causes, but their relative contribution remains unclear. Dysfunction of alpha-synuclein
[...] Read more.
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer's disease (AD) and represents a large health burden to society. Genetic and oxidative risk factors have been proposed as possible causes, but their relative contribution remains unclear. Dysfunction of alpha-synuclein (α-syn) has been associated with PD due to its increased presence, together with iron, in Lewy bodies. Brain oxidative damage caused by iron may be partly mediated by α-syn oligomerization during PD pathology. Also, α-syn gene dosage can cause familial PD and inhibition of its gene expression by blocking translation via a newly identified Iron Responsive Element-like RNA sequence in its 5’-untranslated region may provide a new PD drug target. Full article
(This article belongs to the Special Issue Advances in Molecular Neuropathology)
Open AccessReview In Vitro Models in Biocompatibility Assessment for Biomedical-Grade Chitosan Derivatives in Wound Management
Int. J. Mol. Sci. 2009, 10(3), 1300-1313; doi:10.3390/ijms10031300
Received: 5 February 2009 / Revised: 12 March 2009 / Accepted: 16 March 2009 / Published: 18 March 2009
Cited by 47 | PDF Full-text (132 KB) | HTML Full-text | XML Full-text
Abstract
One of the ultimate goals of wound healing research is to find effective healing techniques that utilize the regeneration of similar tissues. This involves the modification of various wound dressing biomaterials for proper wound management. The biopolymer chitosan (b-1,4-D-glucosamine) has natural biocompatibility and
[...] Read more.
One of the ultimate goals of wound healing research is to find effective healing techniques that utilize the regeneration of similar tissues. This involves the modification of various wound dressing biomaterials for proper wound management. The biopolymer chitosan (b-1,4-D-glucosamine) has natural biocompatibility and biodegradability that render it suitable for wound management. By definition, a biocompatible biomaterial does not have toxic or injurious effects on biological systems. Chemical and physical modifications of chitosan influence its biocompatibility and biodegradability to an uncertain degree. Hence, the modified biomedical-grade of chitosan derivatives should be pre-examined in vitro in order to produce high-quality, biocompatible dressings. In vitro toxicity examinations are more favorable than those performed in vivo, as the results are more reproducible and predictive. In this paper, basic in vitro tools were used to evaluate cellular and molecular responses with regard to the biocompatibility of biomedical-grade chitosan. Three paramount experimental parameters of biocompatibility in vitro namely cytocompatibility, genotoxicity and skin pro-inflammatory cytokine expression, were generally reviewed for biomedical-grade chitosan as wound dressing. Full article
(This article belongs to the Special Issue Biocompatibility of Materials)
Open AccessReview Mechanism of Suppression of Protein Aggregation by α-Crystallin
Int. J. Mol. Sci. 2009, 10(3), 1314-1345; doi:10.3390/ijms10031314
Received: 30 January 2009 / Revised: 13 March 2009 / Accepted: 18 March 2009 / Published: 19 March 2009
Cited by 35 | PDF Full-text (474 KB) | HTML Full-text | XML Full-text
Abstract
This review summarizes experimental data illuminating the mechanism of suppression of heat-induced protein aggregation by a-crystallin, one of the small heat shock proteins. The dynamic light scattering data show that the initial stage of thermal aggregation of proteins is the formation of the
[...] Read more.
This review summarizes experimental data illuminating the mechanism of suppression of heat-induced protein aggregation by a-crystallin, one of the small heat shock proteins. The dynamic light scattering data show that the initial stage of thermal aggregation of proteins is the formation of the initial aggregates involving hundreds of molecules of the denatured protein. Further sticking of the starting aggregates proceeds in a regime of diffusion-limited cluster-cluster aggregation. The protective effect of a-crystallin is due to transition of the aggregation process to the regime of reaction-limited cluster-cluster aggregation, wherein the sticking probability for the colliding particles becomes lower than unity. Full article
(This article belongs to the Special Issue Protein Folding 2009)
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Open AccessReview Participation of Low Molecular Weight Electron Carriers in Oxidative Protein Folding
Int. J. Mol. Sci. 2009, 10(3), 1346-1359; doi:10.3390/ijms10031346
Received: 3 February 2009 / Revised: 8 March 2009 / Accepted: 17 March 2009 / Published: 20 March 2009
Cited by 5 | PDF Full-text (249 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative protein folding is mediated by a proteinaceous electron relay system, in which the concerted action of protein disulfide isomerase and Ero1 delivers the electrons from thiol groups to the final acceptor. Oxygen appears to be the final oxidant in aerobic living organisms,
[...] Read more.
Oxidative protein folding is mediated by a proteinaceous electron relay system, in which the concerted action of protein disulfide isomerase and Ero1 delivers the electrons from thiol groups to the final acceptor. Oxygen appears to be the final oxidant in aerobic living organisms, although the existence of alternative electron acceptors, e.g. fumarate or nitrate, cannot be excluded. Whilst the protein components of the system are well-known, less attention has been turned to the role of low molecular weight electron carriers in the process. The function of ascorbate, tocopherol and vitamin K has been raised recently. In vitro and in vivo evidence suggests that these redox-active compounds can contribute to the functioning of oxidative folding. This review focuses on the participation of small molecular weight redox compounds in oxidative protein folding. Full article
(This article belongs to the Special Issue Protein Folding 2009)
Open AccessReview Slow Unfolding of Monomeric Proteins from Hyperthermophiles with Reversible Unfolding
Int. J. Mol. Sci. 2009, 10(3), 1369-1385; doi:10.3390/ijms10031369
Received: 28 January 2009 / Revised: 19 March 2009 / Accepted: 23 March 2009 / Published: 24 March 2009
Cited by 11 | PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract
Based on the differences in their optimal growth temperatures microorganisms can be classified into psychrophiles, mesophiles, thermophiles, and hyperthermophiles. Proteins from hyperthermophiles generally exhibit greater stability than those from other organisms. In this review, we collect data about the stability and folding of
[...] Read more.
Based on the differences in their optimal growth temperatures microorganisms can be classified into psychrophiles, mesophiles, thermophiles, and hyperthermophiles. Proteins from hyperthermophiles generally exhibit greater stability than those from other organisms. In this review, we collect data about the stability and folding of monomeric proteins from hyperthermophilies with reversible unfolding, from the equilibrium and kinetic aspects. The results indicate that slow unfolding is a general strategy by which proteins from hyperthermophiles adapt to higher temperatures. Hydrophobic interaction is one of the factors in the molecular mechanism of the slow unfolding of proteins from hyperthermophiles. Full article
(This article belongs to the Special Issue Protein Folding 2009)
Open AccessReview Molecular Pathogenesis of Alzheimer’s Disease: Reductionist versus Expansionist Approaches
Int. J. Mol. Sci. 2009, 10(3), 1386-1406; doi:10.3390/ijms10031386
Received: 27 February 2009 / Revised: 20 March 2009 / Accepted: 23 March 2009 / Published: 26 March 2009
Cited by 23 | PDF Full-text (239 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is characterized clinically by dementia and pathologically by two hallmark lesions, senile plaques and neurofibrillary tangles. About a quarter century ago these hallmark lesions were purified and their protein constituents identified, precipitating an avalanche of molecular studies as well as
[...] Read more.
Alzheimer’s disease (AD) is characterized clinically by dementia and pathologically by two hallmark lesions, senile plaques and neurofibrillary tangles. About a quarter century ago these hallmark lesions were purified and their protein constituents identified, precipitating an avalanche of molecular studies as well as substantial optimism about successful therapeutic intervention. In 2009, we now have copious knowledge on the biochemical cascades that produce these proteins, the different modifications and forms in which these proteins exist, and the ability to selectively target these proteins for therapeutic intervention on an experimental basis. At the same time, there has been no discernible alteration in the natural course of AD in humans. While it may be that the complexity of AD will exceed our capacity to make significant treatment progress for decades or more, a paradigm shift from the reductionism that defines amyloid-β and tau hypotheses, to one that more accurately reflects the meaning of neuropathological changes, may be warranted. We and others have demonstrated that AD pathology is a manifestation of cellular adaptation, specifically as a defense against oxidative injury. As such, AD pathology is therefore a host response rather than a manifestation of cytotoxic protein injury, and is unlikely to be a fruitful target for therapeutic intervention. An “expansionist” view of the disease, we believe, with oxidative stress as a pleiotropic and upstream process, more aptly describes the relationship between various and numerous molecular alterations and clinical disease. Full article
(This article belongs to the Special Issue Advances in Molecular Neuropathology)

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