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Int. J. Mol. Sci., Volume 14, Issue 6 (June 2013), Pages 10683-12913

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Open AccessArticle Ordering of Polystyrene Nanoparticles on Substrates Pre-Coated with Different Polyelectrolyte Architectures
Int. J. Mol. Sci. 2013, 14(6), 12893-12913; https://doi.org/10.3390/ijms140612893
Received: 8 April 2013 / Revised: 15 May 2013 / Accepted: 27 May 2013 / Published: 20 June 2013
Cited by 2 | PDF Full-text (22880 KB) | HTML Full-text | XML Full-text
Abstract
Adjusting the inter-particle distances in ordered nanoparticle arrays can create new nano-devices and is of increasing importance to a number of applications such as nanoelectronics and optical devices. The assembly of negatively charged polystyrene (PS) nanoparticles (NPs) on Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes, quaternized
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Adjusting the inter-particle distances in ordered nanoparticle arrays can create new nano-devices and is of increasing importance to a number of applications such as nanoelectronics and optical devices. The assembly of negatively charged polystyrene (PS) nanoparticles (NPs) on Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes, quaternized PDMAEMA brushes and Si/PEI/(PSS/PAH)2, was studied using dip- and spin-coating techniques. By dip-coating, two dimensional (2-D), randomly distributed non-close packed particle arrays were assembled on Si/PEI/(PSS/PAH)2 and PDMAEMA brushes. The inter-particle repulsion leads to lateral mobility of the particles on these surfaces. The 200 nm diameter PS NPs tended to an inter-particle distance of 350 to 400 nm (center to center). On quaternized PDMAEMA brushes, the strong attractive interaction between the NPs and the brush dominated, leading to clustering of the particles on the brush surface. Particle deposition using spin-coating at low spin rates resulted in hexagonal close-packed multilayer structures on Si/PEI/(PSS/PAH)2. Close-packed assemblies with more pronounced defects are also observed on PDMAEMA brushes and QPDMAEMA brushes. In contrast, randomly distributed monolayer NP arrays were achieved at higher spin rates on all polyelectrolyte architectures. The area fraction of the particles decreased with increasing spin rate. Full article
(This article belongs to the Special Issue Self-Assembled Soft Matter Nanostructures at Interfaces)
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Open AccessArticle A Novel Perspective and Approach to Intestinal Octreotide Absorption: Sinomenine-Mediated Reversible Tight Junction Opening and Its Molecular Mechanism
Int. J. Mol. Sci. 2013, 14(6), 12873-12892; https://doi.org/10.3390/ijms140612873
Received: 22 May 2013 / Revised: 5 June 2013 / Accepted: 7 June 2013 / Published: 20 June 2013
Cited by 4 | PDF Full-text (1338 KB) | HTML Full-text | XML Full-text
Abstract
In this work, we assessed the effects of sinomenine (SN) on intestinal octreotide (OCT) absorption both in Caco-2 cell monolayers and in rats. We also investigated the molecular mechanisms of tight junction (TJ) disruption and recovery by SN-mediated changes in the claudin-1 and
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In this work, we assessed the effects of sinomenine (SN) on intestinal octreotide (OCT) absorption both in Caco-2 cell monolayers and in rats. We also investigated the molecular mechanisms of tight junction (TJ) disruption and recovery by SN-mediated changes in the claudin-1 and protein kinase C (PKC) signaling pathway. The data showed that exposure to SN resulted in a significant decrease in the expression of claudin-1, which represented TJ weakening and paracellular permeability enhancement. Then, the recovery of TJ after SN removal required an increase in claudin-1, which demonstrated the transient and reversible opening for TJ. Meanwhile, the SN-mediated translocation of PKC-α from the cytosol to the membrane was found to prove PKC activation. Finally, SN significantly improved the absolute OCT bioavailability in rats and the transport rate in Caco-2 cell monolayers. We conclude that SN has the ability to enhance intestinal OCT absorption and that these mechanisms are related at least in part to the important role of claudin-1 in SN-mediated, reversible TJ opening via PKC activation. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessArticle Detection of Promyelocytic Leukemia/Retinoic Acid Receptor α (PML/RARα) Fusion Gene with Functionalized Graphene Oxide
Int. J. Mol. Sci. 2013, 14(6), 12863-12872; https://doi.org/10.3390/ijms140612863
Received: 25 March 2013 / Revised: 30 May 2013 / Accepted: 9 June 2013 / Published: 20 June 2013
Cited by 2 | PDF Full-text (396 KB) | HTML Full-text | XML Full-text
Abstract
An attempt was made to use functionalized graphene oxide (GO) to detect the Promyelocytic leukemia/Retinoic acid receptor α fusion gene (PML/RARα fusion gene), a marker gene of acute promyelocytic leukemia. The functionalized GO was prepared by chemical exfoliation method, followed by
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An attempt was made to use functionalized graphene oxide (GO) to detect the Promyelocytic leukemia/Retinoic acid receptor α fusion gene (PML/RARα fusion gene), a marker gene of acute promyelocytic leukemia. The functionalized GO was prepared by chemical exfoliation method, followed by a polyethylene glycol grafting. It is found that the functionalized GO can selectively adsorb the fluorescein isothiocyanate (FITC)-labeled single-stranded DNA probe and quench its fluorescence. The probe can be displaced by the PML/RARα fusion gene to restore the fluorescence, which can be detected by laser confocal microscopy and flow cytometry. These can be used to detect the presence of the PML/RARα fusion gene. This detection method is verified to be fast, simple and reliable. Full article
Open AccessArticle A Novel Low Temperature PCR Assured High-Fidelity DNA Amplification
Int. J. Mol. Sci. 2013, 14(6), 12853-12862; https://doi.org/10.3390/ijms140612853
Received: 17 May 2013 / Revised: 5 June 2013 / Accepted: 7 June 2013 / Published: 20 June 2013
Cited by 4 | PDF Full-text (936 KB) | HTML Full-text | XML Full-text
Abstract
As previously reported, a novel low temperature (LoTemp) polymerase chain reaction (PCR) catalyzed by a moderately heat-resistant (MHR) DNA polymerase with a chemical-assisted denaturation temperature set at 85 °C instead of the conventional 94–96 °C can achieve high-fidelity DNA amplification of a target
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As previously reported, a novel low temperature (LoTemp) polymerase chain reaction (PCR) catalyzed by a moderately heat-resistant (MHR) DNA polymerase with a chemical-assisted denaturation temperature set at 85 °C instead of the conventional 94–96 °C can achieve high-fidelity DNA amplification of a target DNA, even after up to 120 PCR thermal cycles. Furthermore, such accurate amplification is not achievable with conventional PCR. Now, using a well-recognized L1 gene segment of the human papillomavirus (HPV) type 52 (HPV-52) as the template for experiments, we demonstrate that the LoTemp high-fidelity DNA amplification is attributed to an unusually high processivity and stability of the MHR DNA polymerase whose high fidelity in template-directed DNA synthesis is independent of non-existent 3'–5' exonuclease activity. Further studies and understanding of the characteristics of the LoTemp PCR technology may facilitate implementation of DNA sequencing-based diagnostics at the point of care in community hospital laboratories. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle Reconstructing a Flavodoxin Oxidoreductase with Early Amino Acids
Int. J. Mol. Sci. 2013, 14(6), 12843-12852; https://doi.org/10.3390/ijms140612843
Received: 9 April 2013 / Revised: 24 May 2013 / Accepted: 13 June 2013 / Published: 19 June 2013
Cited by 5 | PDF Full-text (658 KB) | HTML Full-text | XML Full-text
Abstract
Primitive proteins are proposed to have utilized organic cofactors more frequently than transition metals in redox reactions. Thus, an experimental validation on whether a protein constituted solely by early amino acids and an organic cofactor can perform electron transfer activity is an urgent
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Primitive proteins are proposed to have utilized organic cofactors more frequently than transition metals in redox reactions. Thus, an experimental validation on whether a protein constituted solely by early amino acids and an organic cofactor can perform electron transfer activity is an urgent challenge. In this paper, by substituting “late amino acids (C, F, M, T, W, and Y)” with “early amino acids (A, L, and V)” in a flavodoxin, we constructed a flavodoxin mutant and evaluated its characteristic properties. The major results showed that: (1) The flavodoxin mutant has structural characteristics similar to wild-type protein; (2) Although the semiquinone and hydroquinone flavodoxin mutants possess lower stability than the corresponding form of wild-type flavodoxin, the redox potential of double electron reduction Em,7 (fld) reached −360 mV, indicating that the flavodoxin mutant constituted solely by early amino acids can exert effective electron transfer activity. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessArticle Overexpression of Arachis hypogaea AREB1 Gene Enhances Drought Tolerance by Modulating ROS Scavenging and Maintaining Endogenous ABA Content
Int. J. Mol. Sci. 2013, 14(6), 12827-12842; https://doi.org/10.3390/ijms140612827
Received: 24 April 2013 / Revised: 21 May 2013 / Accepted: 31 May 2013 / Published: 19 June 2013
Cited by 28 | PDF Full-text (6236 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
AhAREB1 (Arachis hypogaea Abscisic-acid Response Element Binding Protein 1) is a member of the basic domain leucine zipper (bZIP)-type transcription factor in peanut. Previously, we found that expression of AhAREB1 was specifically induced by abscisic acid (ABA), dehydration and drought. To
[...] Read more.
AhAREB1 (Arachis hypogaea Abscisic-acid Response Element Binding Protein 1) is a member of the basic domain leucine zipper (bZIP)-type transcription factor in peanut. Previously, we found that expression of AhAREB1 was specifically induced by abscisic acid (ABA), dehydration and drought. To understand the drought defense mechanism regulated by AhAREB1, transgenic Arabidopsis overexpressing AhAREB1 was conducted in wild-type (WT), and a complementation experiment was employed to ABA non-sensitivity mutant abi5 (abscisic acid-insensitive 5). Constitutive expression of AhAREB1 confers water stress tolerance and is highly sensitive to exogenous ABA. Microarray and further real-time PCR analysis revealed that drought stress, reactive oxygen species (ROS) scavenging, ABA synthesis/metabolism-related genes and others were regulated in transgenic Arabidopsis overexpressing AhAREB1. Accordingly, low level of ROS, but higher ABA content was detected in the transgenic Arabidopsis plants’ overexpression of AhAREB1. Taken together, it was concluded that AhAREB1 modulates ROS accumulation and endogenous ABA level to improve drought tolerance in transgenic Arabidopsis. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessReview Putative Genes Involved in Saikosaponin Biosynthesis in Bupleurum Species
Int. J. Mol. Sci. 2013, 14(6), 12806-12826; https://doi.org/10.3390/ijms140612806
Received: 22 April 2013 / Revised: 13 June 2013 / Accepted: 14 June 2013 / Published: 19 June 2013
Cited by 9 | PDF Full-text (869 KB) | HTML Full-text | XML Full-text
Abstract
Alternative medicinal agents, such as the herb Bupleurum, are increasingly used in modern medicine to supplement synthetic drugs. First, we present a review of the currently known effects of triterpene saponins-saikosaponins of Bupleurum species. The putative biosynthetic pathway of saikosaponins in Bupleurum species
[...] Read more.
Alternative medicinal agents, such as the herb Bupleurum, are increasingly used in modern medicine to supplement synthetic drugs. First, we present a review of the currently known effects of triterpene saponins-saikosaponins of Bupleurum species. The putative biosynthetic pathway of saikosaponins in Bupleurum species is summarized, followed by discussions on identification and characterization of genes involved in the biosynthesis of saikosaponins. The purpose is to provide a brief review of gene extraction, functional characterization of isolated genes and assessment of expression patterns of genes encoding enzymes in the process of saikosaponin production in Bupleurum species, mainly B. kaoi. We focus on the effects of MeJA on saikosaponin production, transcription patterns of genes involved in biosynthesis and on functional depiction. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
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Open AccessReview Sesquiterpenoids Lactones: Benefits to Plants and People
Int. J. Mol. Sci. 2013, 14(6), 12780-12805; https://doi.org/10.3390/ijms140612780
Received: 26 April 2013 / Revised: 24 May 2013 / Accepted: 31 May 2013 / Published: 19 June 2013
Cited by 130 | PDF Full-text (539 KB) | HTML Full-text | XML Full-text
Abstract
Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as pharmaceutical agents, due to their potential for the treatment of cardiovascular disease and cancer. This review highlights the
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Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as pharmaceutical agents, due to their potential for the treatment of cardiovascular disease and cancer. This review highlights the role of sesquiterpene lactones endogenously in the plants that produce them, and explores mechanisms by which they interact in animal and human consumers of these plants. Several mechanisms are proposed for the reduction of inflammation and tumorigenesis at potentially achievable levels in humans. Plants can be classified by their specific array of produced sesquiterpene lactones, showing high levels of translational control. Studies of folk medicines implicate sesquiterpene lactones as the active ingredient in many treatments for other ailments such as diarrhea, burns, influenza, and neurodegradation. In addition to the anti-inflammatory response, sesquiterpene lactones have been found to sensitize tumor cells to conventional drug treatments. This review explores the varied ecological roles of sesquiterpenes in the plant producer, depending upon the plant and the compound. These include allelopathy with other plants, insects, and microbes, thereby causing behavioural or developmental modification to these secondary organisms to the benefit of the sesquiterpenoid producer. Some sesquiterpenoid lactones are antimicrobial, disrupting the cell wall of fungi and invasive bacteria, whereas others protect the plant from environmental stresses that would otherwise cause oxidative damage. Many of the compounds are effective due to their bitter flavor, which has obvious implications for human consumers. The implications of sesquiterpenoid lactone qualities for future crop production are discussed. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
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Open AccessArticle Construction of the Coding Sequence of the Transcription Variant 2 of the Human Renalase Gene and Its Expression in the Prokaryotic System
Int. J. Mol. Sci. 2013, 14(6), 12764-12779; https://doi.org/10.3390/ijms140612764
Received: 14 May 2013 / Revised: 23 May 2013 / Accepted: 5 June 2013 / Published: 19 June 2013
Cited by 9 | PDF Full-text (944 KB) | HTML Full-text | XML Full-text
Abstract
Renalase is a recently discovered protein, involved in regulation of blood pressure in humans and animals. Although several splice variants of human renalase mRNA transcripts have been recognized, only one protein product, hRenalase1, has been found so far. In this study, we have
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Renalase is a recently discovered protein, involved in regulation of blood pressure in humans and animals. Although several splice variants of human renalase mRNA transcripts have been recognized, only one protein product, hRenalase1, has been found so far. In this study, we have used polymerase chain reaction (PCR)-based amplification of individual exons of the renalase gene and their joining for construction of full-length hRenalase2 coding sequence followed by expression of hRenalase2 as a polyHis recombinant protein in Escherichia coli cells. To date this is the first report on synthesis and purification of hRenalase2. Applicability of this approach was verified by constructing hRenalase1 coding sequence, its sequencing and expression in E. coli cells. hRenalase1 was used for generation of polyclonal antiserum in sheep. Western blot analysis has shown that polyclonal anti-renalase1 antibodies effectively interact with the hRenalase2 protein. The latter suggests that some functions and expression patterns of hRenalase1 documented by antibody-based data may be attributed to the presence of hRenalase2. The realized approach may be also used for construction of coding sequences of various (especially weakly expressible) genes, their transcript variants, etc. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessReview Role of CBFs as Integrators of Chloroplast Redox, Phytochrome and Plant Hormone Signaling during Cold Acclimation
Int. J. Mol. Sci. 2013, 14(6), 12729-12763; https://doi.org/10.3390/ijms140612729
Received: 10 April 2013 / Revised: 24 May 2013 / Accepted: 6 June 2013 / Published: 18 June 2013
Cited by 55 | PDF Full-text (818 KB) | HTML Full-text | XML Full-text
Abstract
Cold acclimation of winter cereals and other winter hardy species is a prerequisite to increase subsequent freezing tolerance. Low temperatures upregulate the expression of C-repeat/dehydration-responsive element binding transcription factors (CBF/DREB1) which in turn induce the expression of COLD-REGULATED (COR) genes. We
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Cold acclimation of winter cereals and other winter hardy species is a prerequisite to increase subsequent freezing tolerance. Low temperatures upregulate the expression of C-repeat/dehydration-responsive element binding transcription factors (CBF/DREB1) which in turn induce the expression of COLD-REGULATED (COR) genes. We summarize evidence which indicates that the integration of these interactions is responsible for the dwarf phenotype and enhanced photosynthetic performance associated with cold-acclimated and CBF-overexpressing plants. Plants overexpressing CBFs but grown at warm temperatures mimic the cold-tolerant, dwarf, compact phenotype; increased photosynthetic performance; and biomass accumulation typically associated with cold-acclimated plants. In this review, we propose a model whereby the cold acclimation signal is perceived by plants through an integration of low temperature and changes in light intensity, as well as changes in light quality. Such integration leads to the activation of the CBF-regulon and subsequent upregulation of COR gene and GA 2-oxidase (GA2ox) expression which results in a dwarf phenotype coupled with increased freezing tolerance and enhanced photosynthetic performance. We conclude that, due to their photoautotrophic nature, plants do not rely on a single low temperature sensor, but integrate changes in light intensity, light quality, and membrane viscosity in order to establish the cold-acclimated state. CBFs appear to act as master regulators of these interconnecting sensing/signaling pathways. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessArticle Dual Delivery of BMP-2 and bFGF from a New Nano-Composite Scaffold, Loaded with Vascular Stents for Large-Size Mandibular Defect Regeneration
Int. J. Mol. Sci. 2013, 14(6), 12714-12728; https://doi.org/10.3390/ijms140612714
Received: 1 March 2013 / Revised: 14 May 2013 / Accepted: 13 June 2013 / Published: 18 June 2013
Cited by 33 | PDF Full-text (2958 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) from nano-composite scaffolds (PLGA/PCL/nHA) loaded with vascular stents (PLCL/Col/nHA) for large bone defect regeneration in rabbit
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The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) from nano-composite scaffolds (PLGA/PCL/nHA) loaded with vascular stents (PLCL/Col/nHA) for large bone defect regeneration in rabbit mandibles. Thirty-six large bone defects were repaired in rabbits using engineering bone composed of allogeneic bone marrow mesenchymal stem cells (BMSCs), bFGF, BMP-2 and scaffolds composed of PLGA/PCL/nHA loaded with PLCL/Col/nHA. The experiments were divided into six groups: BMSCs/bFGF/BMP-2/scaffold, BMSCs/BMP-2/scaffold, BMSCs/bFGF/scaffold, BMSCs/scaffold, scaffold alone and no treatment. Sodium alginate hydrogel was used as the carrier for BMP-2 and bFGF and its features, including gelling, degradation and controlled release properties, was detected by the determination of gelation and degradation time coupled with a controlled release study of bovine serum albumin (BSA). AlamarBlue assay and alkaline phosphatase (ALP) activity were used to evaluate the proliferation and osteogenic differentiation of BMSCs in different groups. X-ray and histological examinations of the samples were performed after 4 and 12 weeks post-implantation to clarify new bone formation in the mandible defects. The results verified that the use of sodium alginate hydrogel as a controlled release carrier has good sustained release ability, and the combined application of bFGF and BMP-2 could significantly promote the proliferation and osteogenic differentiation of BMSCs (p < 0.05 or p < 0.01). In addition, X-ray and histological examinations of the samples exhibited that the dual release group had significantly higher bone formation than the other groups. The above results indicate that the delivery of both growth factors could enhance new bone formation and vascularization compared with delivery of BMP-2 or bFGF alone, and may supply a promising way of repairing large bone defects in bone tissue engineering. Full article
(This article belongs to the Section Materials Science)
Open AccessReview Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins
Int. J. Mol. Sci. 2013, 14(6), 12696-12713; https://doi.org/10.3390/ijms140612696
Received: 10 April 2013 / Revised: 11 May 2013 / Accepted: 5 June 2013 / Published: 17 June 2013
Cited by 41 | PDF Full-text (233 KB) | HTML Full-text | XML Full-text
Abstract
The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and
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The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Open AccessArticle Tracking the Interplay between Bound Peptide and the Lid Domain of DnaK, Using Molecular Dynamics
Int. J. Mol. Sci. 2013, 14(6), 12675-12695; https://doi.org/10.3390/ijms140612675
Received: 4 March 2013 / Revised: 10 May 2013 / Accepted: 4 June 2013 / Published: 17 June 2013
Cited by 2 | PDF Full-text (772 KB) | HTML Full-text | XML Full-text
Abstract
Hsp70 chaperones consist of two functional domains: the 44 kDa Nucleotide Binding Domain (NBD), that binds and hydrolyses ATP, and the 26 kDa Substrate Binding Domain (SBD), which binds unfolded proteins and reactivates them, utilizing energy obtained from nucleotide hydrolysis. The structure of
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Hsp70 chaperones consist of two functional domains: the 44 kDa Nucleotide Binding Domain (NBD), that binds and hydrolyses ATP, and the 26 kDa Substrate Binding Domain (SBD), which binds unfolded proteins and reactivates them, utilizing energy obtained from nucleotide hydrolysis. The structure of the SBD of the bacterial Hsp70, DnaK, consists of two sub-domains: A β-sandwich part containing the hydrophobic cavity to which the hepta-peptide NRLLLTG (NR) is bound, and a segment made of 5 α-helices, called the “lid” that caps the top of the β-sandwich domain. In the present study we used the Escherichia coli Hsp70, DnaK, as a model for Hsp70 proteins, focusing on its SBD domain, examining the changes in the lid conformation. We deliberately decoupled the NBD from the SBD, limiting the study to the structure of the SBD section, with an emphasis on the interaction between the charges of the peptide with the residues located in the lid. Molecular dynamics simulations of the complex revealed significant mobility within the lid structure; as the structure was released from the forces operating during the crystallization process, the two terminal helices established a contact with the positive charge at the tip of the peptide. This contact is manifested only in the presence of electrostatic attraction. The observed internal motions within the lid provide a molecular role for the function of this sub-domain during the reaction cycle of Hsp 70 chaperones. Full article
(This article belongs to the collection Protein Folding)
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Open AccessArticle Design, Synthesis, Biological Activity and Molecular Dynamics Studies of Specific Protein Tyrosine Phosphatase 1B Inhibitors over SHP-2
Int. J. Mol. Sci. 2013, 14(6), 12661-12674; https://doi.org/10.3390/ijms140612661
Received: 15 April 2013 / Revised: 2 June 2013 / Accepted: 3 June 2013 / Published: 17 June 2013
Cited by 3 | PDF Full-text (410 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Over expressing in PTPN1 (encoding Protein tyrosine phosphatase 1B, PTP1B), a protein tyrosine phosphatase (PTP) that plays an overall positive role in insulin signaling, is linked to the pathogenesis of diabetes and obesity. The relationship between PTP1B and human diseases exhibits PTP1B as
[...] Read more.
Over expressing in PTPN1 (encoding Protein tyrosine phosphatase 1B, PTP1B), a protein tyrosine phosphatase (PTP) that plays an overall positive role in insulin signaling, is linked to the pathogenesis of diabetes and obesity. The relationship between PTP1B and human diseases exhibits PTP1B as the target to treat these diseases. In this article, small weight molecules of the imidazolidine series were screened from databases and optimized on silicon as the inhibitors of PTP1B based on the steric conformation and electronic configuration of thiazolidinedione (TZD) compounds. The top three candidates were tested using an in vitro biological assay after synthesis. Finally, we report a novel inhibitor, Compound 13, that specifically inhibits PTP1B over the closely related phosphatase Src homology 2 (SH2) domain-containing phosphatase 2 (SHP-2) at 80 μΜ. Its IC50 values are reported in this paper as well. This compound was further verified by computer analysis for its ability to combine the catalytic domains of PTP1B and SHP-2 by molecular dynamics (MD) simulations. Full article
Open AccessArticle Human Chorionic Gonadotropin Beta Subunit Genes CGB1 and CGB2 are Transcriptionally Active in Ovarian Cancer
Int. J. Mol. Sci. 2013, 14(6), 12650-12660; https://doi.org/10.3390/ijms140612650
Received: 1 March 2013 / Revised: 28 March 2013 / Accepted: 9 May 2013 / Published: 17 June 2013
Cited by 4 | PDF Full-text (253 KB) | HTML Full-text | XML Full-text
Abstract
Human chorionic gonadotropin beta subunit (CGB) is a marker of pregnancy as well as trophoblastic and nontrophoblastic tumors. CGB is encoded by a cluster of six genes, of which type II genes (CGB3/9, 5 and 8) have been shown to
[...] Read more.
Human chorionic gonadotropin beta subunit (CGB) is a marker of pregnancy as well as trophoblastic and nontrophoblastic tumors. CGB is encoded by a cluster of six genes, of which type II genes (CGB3/9, 5 and 8) have been shown to be upregulated in relation to type I genes (CGB6/7) in both placentas and tumors. Recent studies revealed that CGB1 and CGB2, originally considered as pseudogenes, might also be active, however, the protein products of these genes have not yet been identified. Our study demonstrates the presence of CGB1 and CGB2 transcripts in ovarian carcinomas. While CGB1 and CGB2 gene activation was not detected in normal ovaries lacking cancerous development, our study demonstrates the presence of CGB1 and CGB2 transcripts in 41% of analyzed ovarian cancer cases. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
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