TY - JOUR AU - Graus, Dorothea AU - Konrad, Kai R. AU - Bemm, Felix AU - Nebioglu, Meliha G. P. AU - Lorey, Christian AU - Duscha, Kerstin AU - Guthoff, Tilman AU - Herrmann, Johannes AU - Ferjani, Ali AU - Cuin, Tracey A. AU - Roelfsema, M. Rob G. AU - Schumacher, Karin AU - Neuhaus, Ekkehard AU - Marten, Irene AU - Hedrich, Rainer T1 - High V-PPase activity is beneficial under high salt loads, but

detrimental without salinity JO - New Phytologist PY - 2018/ VL - 219 IS - SP - EP - UR - DO - 10.1111/nph.15280 KW - KW - KW - cells KW - KW - leaf KW - myown KW - pyrophosphatase KW - KW - salt KW - stress KW - vacuole L1 - SN - N1 - N1 - AB - * The membrane-bound proton-pumping pyrophosphatase (V-PPase), together with the

V-type H+-ATPase, generates the proton motive force that drives vacuolar membrane solute

transport. Transgenic plants constitutively overexpressing V-PPases were shown to have

improved salinity tolerance, but the relative impact of increasing PPi hydrolysis and protonpumping

functions has yet to be dissected.

* For a better understanding of the molecular processes underlying V-PPase-dependent salt

tolerance, we transiently overexpressed the pyrophosphate-driven proton pump (NbVHP) in

Nicotiana benthamiana leaves and studied its functional properties in relation to salt treatment

by primarily using patch-clamp, impalement electrodes and pH imaging.

* NbVHP overexpression led to higher vacuolar proton currents and vacuolar acidification.

After 3 d in salt-untreated conditions, V-PPase-overexpressing leaves showed a drop in

photosynthetic capacity, plasma membrane depolarization and eventual leaf necrosis. Salt,

however, rescued NbVHP-hyperactive cells from cell death. Furthermore, a salt-induced rise

in V-PPase but not of V-ATPase pump currents was detected in nontransformed plants.

* The results indicate that under normal growth conditions, plants need to regulate the

V-PPase pump activity to avoid hyperactivity and its negative feedback on cell viability.

Nonetheless, V-PPase proton pump function becomes increasingly important under salt stress

for generating the pH gradient necessary for vacuolar proton-coupled Na+ sequestration. ER - TY - JOUR AU - Noureini, S.K. AU - Kheirabadi, M. AU - Masoumi, F. AU - Khosrogerdi, F. AU - Zarei, Y. AU - Suarez-Rozas, C. AU - Salas-Norambuena, J. AU - Cassels, B.K. T1 - Telomerase Inhibition by a New Synthetic Derivative of the Aporphine Alkaloid Boldine JO - International Journal of Molecular Sciences PY - 2018/ VL - 19 IS - 4 SP - EP - UR - /brokenurl#://WOS:000434978700318 DO - 10.3390/ijms19041239 KW - apoptosis KW - KW - assay KW - binding KW - boldine KW - KW - cells KW - KW - derivative KW - KW - domain KW - KW - dqcauchile KW - inhibition KW - KW - n-benzylsecoboldine KW - KW - site KW - KW - stress KW - KW - telomerase L1 - SN - N1 - N1 - AB - Telomerase, the enzyme responsible for cell immortality, is an important target in anti-cancer drug discovery. Boldine, an abundant aporphine alkaloid of Peumus boldus, is known to inhibit telomerase at non-toxic concentrations. Cytotoxicity of N-benzylsecoboldine hydrochloride (BSB), a synthetic derivative of boldine, was determined using the MTT method in MCF7 and MDA-MB231 cells. Aliquots of cell lysates were incubated with various concentrations of BSB in qTRAP (quantitative telomere repeat amplification protocol)-ligand experiments before substrate elongation by telomerase or amplification by hot-start Taq polymerase. The crystal structure of TERT, the catalytic subunit of telomerase from Tribolium castaneum, was used for docking and molecular dynamics analysis. The qTRAP-ligand data gave an IC50 value of about 0.17 +/- 0.1 mu M for BSB, roughly 400 times stronger than boldine, while the LD50 in the cytotoxicity assays were 12.5 and 21.88 mu M, respectively, in cells treated for 48 h. Although both compounds interacted well with the active site, MD analysis suggests a second binding site with which BSB interacts via two hydrogen bonds, much more strongly than boldine. Theoretical analyses also evaluated the IC50 for BSB as submicromolar. BSB, with greater hydrophobicity and flexibility than boldine, represents a promising structure to inhibit telomerase at non-toxic concentrations. ER - TY - JOUR AU - Celis, F. AU - Garcia, M. AU - Diaz-Fleming, G. AU - Campos-Vallette, M. T1 - A Review of Raman, Surface-Enhanced Raman Scattering (Sers) and Related Spectroscopic Techniques Applied to Biomolecules in Biomaterials JO - Journal of the Chilean Chemical Society PY - 2017/ VL - 62 IS - 3 SP - 3627 EP - 3632 UR - /brokenurl#://WOS:000417443500015 DO - KW - adsorption KW - KW - ag KW - biomaterials KW - KW - biomolecules KW - KW - bone KW - KW - calcium-phosphate KW - KW - cells KW - KW - dqcauchile KW - fragments KW - KW - gold KW - living KW - nanoparticles KW - KW - peptide KW - raman KW - KW - sers KW - KW - silver KW - terminal KW - ultraviolet L1 - SN - N1 - N1 - AB - The development of new biomaterials has gained increasing attention in the last decade. One of the most important aspects in the development of these new materials is to understand the chemical cues presents in the native niche. Among all the techniques currently available for measuring those interactions, Raman spectroscopy offers a unique and non-invasive tool for exploring the behavior of the components within a given biomaterial and their surrounding microenvironment. This technique exploits the unique molecular vibrational fingerprints for pinpointing those interactions. The vibrational response can be improved to the single molecule level, in the presence of metal nanoparticles (NPs) with plasmonic properties (silver, gold and copper) in the so-called SurfaceEnhanced Raman Scattering (SERS), which can be used for in-situ measurements. Another technique recently developed is the Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy (SHINERS), which overcomes signal contamination from chemical interactions between biomolecules and the metal surface; it does this by coating the metal surface with an inert layer of alumina or silica. In the present contribution, the role and the applications of Raman, SERS and related spectroscopic techniques in the study of biomolecules in biomaterials are reviewed and discussed. ER - TY - JOUR AU - Garcia-Beltran, O. AU - Mena, N.P. AU - Aguirre, P. AU - Barriga-Gonzalez, G. AU - Galdamez, A. AU - Nagles, E. AU - Adasme, T. AU - Hidalgo, C. AU - Nunez, M.T. T1 - Development of an Iron-Selective Antioxidant Probe with Protective Effects on Neuronal Function JO - Plos One PY - 2017/ VL - 12 IS - 12 SP - EP - UR - /brokenurl#://WOS:000417648600030 DO - 10.1371/journal.pone.0189043 KW - calcium KW - cells KW - KW - coumarins KW - KW - deficiency KW - KW - dqcauchile KW - fluorescence KW - fluorescence KW - KW - fragmentation KW - KW - iron KW - KW - labile KW - mitochondrial KW - on KW - oxidative KW - parkinsons-disease KW - KW - probes KW - KW - sh-sy5y KW - stress L1 - SN - N1 - N1 - AB - Iron accumulation, oxidative stress and calcium signaling dysregulation are common pathognomonic signs of several neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, Friedreich ataxia and Huntington's disease. Given their therapeutic potential, the identification of multifunctional compounds that suppress these damaging features is highly desirable. Here, we report the synthesis and characterization of N-(1,3-dihydroxy- 2-(hydroxymethyl) propan-2-yl)-2-(7-hydroxy-2-oxo-2H-chromen-4-yl) acetamide, named CT51, which exhibited potent free radical neutralizing activity both in vitro and in cells. CT51 bound Fe2+ with high selectivity and Fe3+ with somewhat lower affinity. Cyclic voltammetric analysis revealed irreversible binding of Fe3+ to CT51, an important finding since stopping Fe2+/Fe3+ cycling in cells should prevent hydroxyl radical production resulting from the Fenton-Haber-Weiss cycle. When added to human neuroblastoma cells, CT51 freely permeated the cell membrane and distributed to both mitochondria and cytoplasm. Intracellularly, CT51 bound iron reversibly and protected against lipid peroxidation. Treatment of primary hippocampal neurons with CT51 reduced the sustained calcium release induced by an agonist of ryanodine receptor-calcium channels. These protective properties of CT51 on cellular function highlight its possible therapeutic use in diseases with significant oxidative, iron and calcium dysregulation. ER - TY - JOUR AU - Inostroza, N. AU - Mendizabal, F. AU - Arratia-P, R., R. AU - Orellana, C. AU - Linares-Flores, C. T1 - Improvement of Photovoltaic Performance by Substituent Effect of Donor and Acceptor Structure of Tpa-Based Dye-Sensitized Solar Cells JO - Journal of Molecular Modeling PY - 2016/ VL - 22 IS - 1 SP - EP - UR - /brokenurl#://WOS:000369312100025 DO - 10.1007/s00894-015-2893-9 KW - absorption KW - alignment KW - KW - approximation KW - KW - cells KW - KW - density KW - design KW - KW - dqcauchile KW - dye-sensitized KW - electron-transfer KW - KW - electronic KW - energy-levels KW - KW - free KW - functional KW - molecular KW - organic KW - organic-dyes KW - KW - porphyrins KW - KW - semiconductor KW - KW - solar KW - spectra KW - KW - surface KW - theory KW - KW - tio2 L1 - SN - N1 - N1 - AB - We report a computational study of a series of organic dyes built with triphenylamine (TPA) as an electron donor group. We designed a set of six dyes called (TPA-n, where n=0-5). In order to enhance the electron-injection process, the electron-donor effect of some specific substituent was studied. Thus, we gave insights into the rational design of organic TPA-based chromophores for use in dye-sensitized solar cells (DSSCs). In addition, we report the HOMO, LUMO, the calculated excited state oxidized potential E-dye*(eV) and the free energy change for electron-injection Delta G(inject)(eV), and the UV-visible absorption bands for TPA-n dyes by a time-dependent density functional theory (TDDFT) procedure at the B3LYP and CAM-B3LYP levels with solvent effect. The results demonstrate that the introduction of the electron-acceptor groups produces an intramolecular charge transfer showing a shift of the absorption wavelengths of TPA-n under studies. ER - TY - JOUR AU - Reineck, Philipp T1 - Plasmonic Hot Electron Solar Cells: The Effect of Nanoparticle Size on Quantum Efficiency JO - PY - 2016/ VL - IS - SP - EP - UR - DO - KW - Cells KW - KW - Efficiency KW - Electron KW - Hot KW - Nanoparticle KW - Plasmonic KW - Quantum KW - Size KW - KW - Solar L1 - SN - N1 - N1 - AB - ER - TY - JOUR AU - Urra, F.A. AU - Weiss-Lopez, B. AU - Araya-Maturana, R. T1 - Determinants of Anti-Cancer Effect of Mitochondrial Electron Transport Chain Inhibitors: Bioenergetic Profile and Metabolic Flexibility of Cancer Cells JO - Current Pharmaceutical Design PY - 2016/ VL - 22 IS - 39 SP - 5998 EP - 6008 UR - /brokenurl#://WOS:000390650400011 DO - 10.2174/1381612822666160719122626 KW - agents KW - KW - alpha-ketoglutarate KW - KW - anti-cancer KW - cancer KW - carboxylation KW - KW - cells KW - KW - complex-i KW - KW - complexes KW - KW - dqcauchile KW - glutamine KW - glutamine-metabolism KW - KW - impairment KW - KW - metabolic KW - metabolism KW - KW - mitochondrial KW - nadh-ubiquinone KW - ovarian-cancer KW - KW - oxidative KW - oxidative-phosphorylation KW - KW - oxidoreductase KW - KW - pancreatic-cancer KW - KW - phosphorylation KW - KW - reductive KW - remodeling KW - KW - respiratory KW - respiratory-chain KW - KW - slow-cycling KW - solid KW - tumor-cells KW - KW - tumors L1 - SN - N1 - N1 - AB - Recent evidence highlights that energy requirements of cancer cells vary greatly from normal cells and they exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation (OXPHOS). Interestingly, mitochondrial electron transport chain (ETC) has been identified as an essential component in bioenergetics, biosynthesis and redox control during proliferation and metastasis of cancer cells. This dependence converts ETC of cancer cells in a promising target to design small molecules with anti-cancer actions. Several small molecules have been described as ETC inhibitors with different consequences on mitochondrial bioenergetics, viability and proliferation of cancer cells, when the substrate availability is controlled to favor either the glycolytic or OXPHOS pathway. These ETC inhibitors can be grouped as 1) inhibitors of a respiratory complex (e.g. rotenoids, vanilloids, alkaloids, biguanides and polyphenols), 2) inhibitors of several respiratory complexes (e.g. capsaicin, ME-344 and epigallocatechin-3 gallate) and 3) inhibitors of ETC activity (e.g. elesclomol and VLX600). Although pharmacological ETC inhibition may produce cell death and a decrease of proliferation of cancer cells, factors such as degree of inhibition of ETC activity by small molecules, bioenergetic profile and metabolic flexibility of different cancer types or subpopulations of cells in a particular cancer type, can affect the impact of the anti-cancer actions. Particularly interesting are the adaptive mechanisms induced by ETC inhibition, such as induction of glutamine-dependent reductive carboxylation, which may offer a strategy to sensitize cancer cells to inhibitors of glutamine metabolism. ER - TY - JOUR AU - Urra, F.A. AU - Cordova-Delgado, M. AU - Lapier, M. AU - Orellana-Manzano, A. AU - Acevedo-Arevalo, L. AU - Pessoa-Mahana, H. AU - Gonzalez-Vivanco, J.M. AU - Martinez-Cifuentes, M. AU - Ramirez-Rodriguez, O. AU - Millas-Vargas, J.P. AU - Weiss-Lopez, B. AU - Pavani, M. AU - Ferreira, J. AU - Araya-Maturana, R. T1 - Small Structural Changes on a Hydroquinone Scaffold Determine the Complex I Inhibition or Uncoupling of Tumoral Oxidative Phosphorylation JO - Toxicology and Applied Pharmacology PY - 2016/ VL - 291 IS - SP - 46 EP - 57 UR - /brokenurl#://WOS:000378100100006 DO - 10.1016/j.taap.2015.12.005 KW - 6-ketocholestanol KW - adenocarcinoma KW - agents KW - KW - anti-cancer KW - apoptosis KW - KW - calu-6 KW - cancer-cells KW - KW - cell KW - cells KW - KW - complex KW - derivatives KW - KW - dqcauchile KW - dysfunction KW - KW - energy-metabolism KW - KW - hydroquinones KW - KW - i KW - KW - liver-mitochondria KW - KW - mitochondrial KW - oxidative KW - phosphorylation KW - KW - respiration KW - KW - ta3 KW - KW - uncouplers L1 - SN - N1 - N1 - AB - Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cell line. Our results indicate that these structural changes modify the effect on OXPHOS, obtaining compounds with three alternative actions: inhibitors of complex I-dependent respiration, uncoupler of OXPHOS and compounds with both actions. To confirm this, the effect of a bicyclic hydroquinone (9) was evaluated in isolated mitochondria. Hydroquinone 9 increased mitochondrial respiration in state 4o without effects on the ADP-stimulated respiration (state 3(ADP)), decreasing the complexes I and II-dependent respiratory control ratio. The effect on mitochondrial respiration was reversed by 6-ketocholestanol addition, indicating that this hydroquinone is a protonophoric uncoupling agent. In intact TA3/Ha cells, hydroquinone 9 caused mitochondrial depolarization, decreasing intracellular ATP and NAD(P)H levels and GSH/GSSG ratio, and slightly increasing the ROS levels. Moreover, it exhibited selective NAD(P)H availability-dependent anti-proliferative effect on cancer cells. Therefore, our results indicate that the ortho-carbonyl hydroquinone scaffold offers the possibility to design compounds with specific actions on OXPHOS of cancer cells. ER - TY - JOUR AU - Tambe, Dhananjay T. AU - Fredberg, Jeffrey J. T1 - And I hope you like jamming too JO - New Journal of Physics PY - 2015/10 VL - 17 IS - 9 SP - EP - UR - http://dx.doi.org/10.1088/1367-2630/17/9/091001 DO - 10.1088/1367-2630/17/9/091001 KW - cancer KW - KW - cells KW - KW - jamming L1 - SN - N1 - N1 - AB - ER - TY - JOUR AU - Garcia-Beltran, O. AU - Mena, N. AU - Yanez, O. AU - Caballero, J. AU - Vargas, V. AU - Nunez, M.T. AU - Cassels, B.K. T1 - Design, Synthesis and Cellular Dynamics Studies in Membranes of a New Coumarin-Based "Turn-Off" Fluorescent Probe Selective for Fe2+ JO - European Journal of Medicinal Chemistry PY - 2013/ VL - 67 IS - SP - 60 EP - 63 UR - /brokenurl#://WOS:000325121800007 DO - 10.1016/j.ejmech.2013.06.022 KW - cells KW - KW - chelatable KW - chelators KW - KW - chemosensor KW - KW - deficiency KW - KW - dqcauchile KW - dynamics KW - KW - fe2+ KW - fe3+ KW - fluorescent KW - ion KW - KW - iron KW - KW - labile KW - molecular KW - probes KW - KW - sensor KW - KW - turn-off L1 - SN - N1 - N1 - AB - A new coumarin-based 'turn-off' fluorescent probe, 7-(diethylamino)-N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-oxo-2H-chromene-3-carboxamide (AGD) was synthesized. This compound is highly selective for ferrous ions (Fe2+) and can reversibly detect them in aqueous medium. The probe localizes to the cell membrane in living cells, where it can detect changes in Fe2+ concentration. Molecular dynamics (MD) simulations indicate that AGD interacts with the lipid bilayer at the level of the glycerol moieties. ER - TY - JOUR AU - Ortlepp, Claudia AU - Steudel, Christine AU - Heiderich, Caroline AU - Koch, Sina AU - Jacobi, Angela AU - Ryser, Martin AU - Brenner, Sebastian AU - Bornhäuser, Martin AU - Brors, Benedikt AU - Hofmann, Wolf-Karsten AU - Ehninger, Gerhard AU - Thiede, Christian T1 - Autotaxin is expressed in FLT3-ITD positive acute myeloid leukemia and hematopoietic stem cells and promotes cell migration and proliferation. JO - Exp Hematol PY - 2013/05 VL - 41 IS - 5 SP - 444 EP - 461.e4 UR - http://dx.doi.org/10.1016/j.exphem.2013.01.007 DO - 10.1016/j.exphem.2013.01.007 KW - /&/ KW - 3 KW - KW - Acute KW - Analysis; KW - Array KW - Blotting KW - KW - Cell KW - Cells KW - KW - Cells; KW - Chain KW - Cultured; KW - Diester KW - Disease; KW - Expression KW - Gene KW - Hematopoietic KW - Humans; KW - Hydrolases KW - KW - Indoles KW - KW - Inhibitors KW - KW - K562 KW - Kinase KW - Leukemia KW - KW - Leukemic KW - KW - Line KW - KW - Line; KW - Lysophosphatidylcholines KW - KW - Lysophospholipids KW - KW - Movement KW - KW - Mutation; KW - Myeloid KW - KW - Oligonucleotide KW - Phosphoric KW - Polymerase KW - Profiling; KW - Proliferation; KW - Protein KW - Reaction; KW - Regulation KW - KW - Repeat KW - Reverse KW - Sequence KW - Sequences KW - KW - Staurosporine KW - KW - Stem KW - Tandem KW - Transcriptase KW - Tumor; KW - Tyrosine KW - Western; KW - analogs KW - derivatives/pharmacology; KW - drug KW - effects/genetics; KW - effects; KW - fms-Like KW - genetics KW - genetics/metabolism/pathology; KW - genetics/metabolism; KW - genetics; KW - metabolism/pharmacology; KW - metabolism; KW - pharmacology; L1 - SN - N1 - N1 - AB - Autotaxin (ATX) has been reported to act as a motility and growth factor in a variety of cancer cells. The ATX protein acts as a secreted lysophospholipase D by converting lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which signals via G-protein-coupled receptors and has important functions in cell migration and proliferation. This study demonstrates that ATX expression is specifically upregulated and functionally active in acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) mutation of the FLT3 receptor gene. Moreover, ATX expression was also found in normal human CD34+ progenitor cells and selected myeloid and lymphoid subpopulations. Enforced expression of mutant FLT3-ITD by retroviral vector transduction increased ATX mRNA in selected cell lines, whereas inhibition of FLT3-ITD signaling by sublethal doses of PKC412 or SU5614 led to a significant downregulation of ATX mRNA and protein levels. In the presence of LPC, ATX expression significantly increased proliferation. LPA induced proliferation, regardless of ATX expression, and induced chemotaxis in all tested human leukemic cell lines and human CD34(+) progenitors. LPC increased chemotaxis only in cells with high expression of endogenous ATX by at least 80 demonstrating the autocrine action of ATX. Inhibition of ATX using a small molecule inhibitor selectively induced killing of ATX-expressing cell lines and reduced motility in these cells. Our data suggest that the production of bioactive LPA through ATX is involved in controlling proliferation and migration during hematopoiesis and that deregulation of ATX contributes to the pathogenesis of AML. ER - TY - JOUR AU - Pinto, Sheena AU - Michel, Chloé AU - Schmidt-Glenewinkel, Hannah AU - Harder, Nathalie AU - Rohr, Karl AU - Wild, Stefan AU - Brors, Benedikt AU - Kyewski, Bruno T1 - Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity. JO - Proc Natl Acad Sci U S A PY - 2013/10 VL - 110 IS - 37 SP - E3497 EP - E3505 UR - http://dx.doi.org/10.1073/pnas.1308311110 DO - 10.1073/pnas.1308311110 KW - Antigenic KW - Autoantigens KW - KW - Cell KW - Cells KW - KW - Differentiation KW - KW - Epithelial KW - Expression; KW - Family; KW - Gene KW - Gland KW - KW - Humans; KW - Multigene KW - Self KW - Thymus KW - Tolerance KW - KW - Variation; KW - classification/cytology/immunology; KW - cytology/immunology KW - genetics/immunology; KW - genetics; L1 - SN - N1 - N1 - AB - Promiscuous expression of numerous tissue-restricted self-antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential to safeguard self-tolerance. A distinct feature of promiscuous gene expression is its mosaic pattern (i.e., at a given time, each self-antigen is expressed only in 1-3% of mTECs). How this mosaic pattern is generated at the single-cell level is currently not understood. Here, we show that subsets of human mTECs expressing a particular TRA coexpress distinct sets of genes. We identified three coexpression groups comprising overlapping and complementary gene sets, which preferentially mapped to certain chromosomes and intrachromosomal gene clusters. Coexpressed gene loci tended to colocalize to the same nuclear subdomain. The TRA subsets aligned along progressive differentiation stages within the mature mTEC subset and, in vitro, interconverted along this sequence. Our data suggest that single mTECs shift through distinct gene pools, thus scanning a sizeable fraction of the overall repertoire of promiscuously expressed self-antigens. These findings have implications for the temporal and spatial (re)presentation of self-antigens in the medulla in the context of tolerance induction. ER - TY - JOUR AU - Urra, F.A. AU - Cordova-Delgado, M. AU - Pessoa-Mahana, H. AU - Ramirez-Rodriguez, O. AU - Weiss-Lopez, B. AU - Ferreira, J. AU - Araya-Maturana, R. T1 - Mitochondria: A Promising Target for Anticancer Alkaloids JO - Current Topics in Medicinal Chemistry PY - 2013/ VL - 13 IS - 17 SP - 2171 EP - 2183 UR - /brokenurl#://WOS:000324801300007 DO - KW - 2 KW - KW - active KW - agent KW - KW - alkaloids KW - KW - apoptosis KW - KW - cancer KW - capsaicin KW - carbazole KW - caspase-dependent KW - cells KW - KW - delivery KW - KW - dqcauchile KW - endoplasmic KW - endoplasmic-reticulum KW - hepatocellular-carcinoma KW - KW - human KW - induces KW - melanoma-cells KW - microtubule-modulating KW - mitochondria KW - KW - mouse KW - nucleotide KW - peptide KW - KW - prostate-cancer KW - reticulum KW - KW - self-assembling KW - stress KW - KW - targeting KW - KW - translocase L1 - SN - N1 - N1 - AB - A great number of alkaloids exhibit high potential in cancer research. Some of them are anticancer drugs with well-defined clinical uses, exerting their action on microtubules dynamics or DNA replication and topology. On the other hand, mitochondria have been recognized as an essential organelle in the establishment of tumor characteristics, especially the resistance to cell death, high proliferative capacity and adaptation to unfavorable cellular environment. Interestingly, many alkaloids exert their anticancer activities affecting selectively some functions of the tumor mitochondria by 1) modulating OXPHOS and ADP/ATP transport, 2) increasing ROS levels and mitochondrial potential dissipation by crosstalk between endoplasmic reticulum (ER) and mitochondria, 3) inducing mitochondria-dependent apoptosis and autophagy, 4) inhibiting mitochondrial metabolic pathways and 5) by alteration of the morphology and biogenesis of this organelle. These antecedents show the relevance of developing research about the effects of alkaloids on functions controlled by tumor mitochondria, offering an attractive target for the design of new alkaloid derivatives, considering organelle-specific delivery strategies. This review describes mitochondria as a central component in the anticancer action of a set of alkaloids, in a way to illustrate the importance of this organelle in medicinal chemistry. ER - TY - JOUR AU - Donovan, Graham M. AU - Lythe, Grant T1 - T-cell movement on the reticular network JO - Journal of Theoretical Biology PY - 2012/02 VL - 295 IS - SP - 59 EP - 67 UR - http://dx.doi.org/10.1016/j.jtbi.2011.11.001 DO - 10.1016/j.jtbi.2011.11.001 KW - brownianmotion KW - KW - cells KW - KW - spatial-networks KW - biological-networks KW - diffusion L1 - SN - N1 - N1 - AB - The idea that the apparently random motion of T cells in lymph nodes is a result of movement on a reticular network (RN) has received support from dynamic imaging experiments and theoretical studies. We present a mathematical representation of the RN consisting of edges connecting vertices that are randomly distributed in three-dimensional space, and models of lymphocyte movement on such networks including constant speed motion along edges and Brownian motion, not in three-dimensional, but only along edges. The simplest model, in which a cell moves with a constant speed along edges, is consistent with mean-squared displacement proportional to time over intervals long enough to include several changes of direction. A non-random distribution of turning angles is one consequence of motion on a preformed network. Confining cell movement to a network does not, in itself, increase the frequency of cell–cell encounters. ER - TY - JOUR AU - Gamba, Andrea AU - Nicodemi, Mario AU - Soriano, Jordi AU - Ott, Albrecht T1 - Critical Behavior and Axis Defining Symmetry Breaking in Hydra Embryonic Development JO - Physical Review Letters PY - 2012/04 VL - 108 IS - SP - EP - UR - http://dx.doi.org/10.1103/physrevlett.108.158103 DO - 10.1103/physrevlett.108.158103 KW - cells KW - KW - embryonic-development KW - KW - latticemodel KW - critical-phenomena L1 - SN - N1 - N1 - AB - The formation of a hollow cellular sphere is often one of the first steps of multicellular embryonic development. In the case of Hydra, the sphere breaks its initial symmetry to form a foot-head axis. During this process a gene, ks1, is increasingly expressed in localized cell domains whose size distribution becomes scale-free at the axis-locking moment. We show that a physical model based solely on the production and exchange of ks1-promoting factors among neighboring cells robustly reproduces the scaling behavior as well as the experimentally observed spontaneous and temperature-directed symmetry breaking. ER - TY - JOUR AU - Westermann, Frank AU - Muth, Daniel AU - Benner, Axel AU - Bauer, Tobias AU - Henrich, Kai-Oliver AU - Oberthuer, André AU - Brors, Benedikt AU - Beissbarth, Tim AU - Vandesompele, Jo AU - Pattyn, Filip AU - Hero, Barbara AU - König, Rainer AU - Fischer, Matthias AU - Schwab, Manfred T1 - Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas. JO - Genome Biol PY - 2008/ VL - 9 IS - 10 SP - EP - UR - http://dx.doi.org/10.1186/gb-2008-9-10-r150 DO - 10.1186/gb-2008-9-10-r150 KW - Analysis; KW - Cells KW - KW - Cultured KW - Disease KW - Expression KW - Gene KW - Genes KW - KW - Genetic; KW - Neoplastic; KW - Neuroblastoma KW - KW - Nuclear KW - Oncogene KW - Progression; KW - Proteins KW - Proteins KW - KW - Proto-Oncogene KW - Regulation KW - KW - Survival KW - Transcription KW - KW - Tumor KW - c-myc KW - KW - genetics/metabolism; KW - genetics/pathology; KW - myc; L1 - SN - N1 - N1 - AB - Amplified MYCN oncogene resulting in deregulated MYCN transcriptional activity is observed in 20% of neuroblastomas and identifies a highly aggressive subtype. In MYCN single-copy neuroblastomas, elevated MYCN mRNA and protein levels are paradoxically associated with a more favorable clinical phenotype, including disseminated tumors that subsequently regress spontaneously (stage 4s-non-amplified). In this study, we asked whether distinct transcriptional MYCN or c-MYC activities are associated with specific neuroblastoma phenotypes.We defined a core set of direct MYCN/c-MYC target genes by applying gene expression profiling and chromatin immunoprecipitation (ChIP, ChIP-chip) in neuroblastoma cells that allow conditional regulation of MYCN and c-MYC. Their transcript levels were analyzed in 251 primary neuroblastomas. Compared to localized-non-amplified neuroblastomas, MYCN/c-MYC target gene expression gradually increases from stage 4s-non-amplified through stage 4-non-amplified to MYCN amplified tumors. This was associated with MYCN activation in stage 4s-non-amplified and predominantly c-MYC activation in stage 4-non-amplified tumors. A defined set of MYCN/c-MYC target genes was induced in stage 4-non-amplified but not in stage 4s-non-amplified neuroblastomas. In line with this, high expression of a subset of MYCN/c-MYC target genes identifies a patient subtype with poor overall survival independent of the established risk markers amplified MYCN, disease stage, and age at diagnosis.High MYCN/c-MYC target gene expression is a hallmark of malignant neuroblastoma progression, which is predominantly driven by c-MYC in stage 4-non-amplified tumors. In contrast, moderate MYCN function gain in stage 4s-non-amplified tumors induces only a restricted set of target genes that is still compatible with spontaneous regression. ER - TY - JOUR AU - Haas, D. AU - Morgenthaler, J. AU - Lacbawan, F. AU - Long, B. AU - Runz, H. AU - Garbade, S. F. AU - Zschocke, J. AU - Kelley, R. I. AU - Okun, J. G. AU - Hoffmann, G. F. AU - Muenke, M. T1 - Abnormal sterol metabolism in holoprosencephaly: studies

in cultured lymphoblasts. JO - J Med Genet PY - 2007/05 VL - 44 IS - 5 SP - 298 EP - 305 UR - http://dx.doi.org/10.1136/jmg.2006.047258 DO - 10.1136/jmg.2006.047258 KW - /&/ KW - Acetates KW - KW - Adult; KW - Carbon KW - Cells KW - KW - Chemicals KW - KW - Child KW - KW - Cholesterol KW - KW - Chromatography-Mass KW - Cultured; KW - Female; KW - Gas KW - Holoprosencephaly KW - KW - Humans; KW - Infant KW - KW - Infant; KW - Lymphocytes KW - KW - Male; KW - Newborn; KW - Organic KW - Preschool; KW - Radioisotopes; KW - Reference KW - Solvents KW - KW - Spectrometry; KW - Standards; KW - Sterols KW - KW - biosynthesis; KW - isolation KW - metabolism; KW - purification/metabolism KW - sfg L1 - SN - N1 - N1 - AB - BACKGROUND: Holoprosencephaly (HPE) is the most common

structural malformation of the developing forebrain in

humans. The aetiology is heterogeneous and remains

unexplained in approximately 75% of patients. OBJECTIVE:

To examine cholesterol biosynthesis in lymphoblastoid cell

lines of 228 patients with HPE, since perturbations of

cholesterol homeostasis are an important model system to

study HPE pathogenesis in animals. METHODS: An in vitro

loading test that clearly identifies abnormal increase of

C27 sterols in lymphoblast-derived cells was developed

using [2-(14)C] acetate as substrate. RESULTS: 22 (9.6

HPE cell lines had abnormal sterol pattern in the in vitro

loading test. In one previously reported patient,

Smith-Lemli-Opitz syndrome was diagnosed, whereas others

also had clearly reduced cholesterol biosynthesis of

uncertain cause. The mean (SD) cholesterol levels were 57p> (15.3 and 82% (4.7 of total sterols in these cell

lines and controls, respectively. The pattern of

accumulating sterols was different from known defects of

cholesterol biosynthesis. In six patients with abnormal

lymphoblast cholesterol metabolism, additional mutations in

genes known to be associated with HPE or chromosomal

abnormalities were observed. CONCLUSIONS: Impaired

cholesterol biosynthesis may be a contributing factor in

the cause of HPE and should be considered in the evaluation

of causes of HPE, even if mutations in HPE-associated genes

have already been found. ER - TY - CONF AU - Pandey, S. AU - Bortei-Doku, A. AU - White, M.H. A2 - T1 - Molecular Dynamics of Biological Ion Channels T2 - 2005 International Semiconductor Device Research Symposium PB - IEEE C1 - PY - 2005/12 VL - IS - SP - 310 EP - 311 UR - https://ieeexplore.ieee.org/document/1596110 DO - 10.1109/ISDRS.2005.1596110 KW - (biology) KW - KW - Analytical KW - Biological KW - Biomembranes KW - KW - CMOS KW - Cells KW - Drugs KW - KW - Fluctuations KW - KW - Green KW - Laplace KW - Nanoelectronics KW - cells KW - KW - equations KW - KW - function KW - KW - models KW - KW - myown KW - technology L1 - SN - N1 - N1 - AB - Ion channels are pores through a cell membrane that allow the exchange of specific ions across them. Understanding the atomistic-level ionic flow through these biological channels is crucial for pharmacology and drug discovery. In addition, the marriage of biological cells and nanoelectronics offers the possibility of new devices with the potential to go beyond the limitations of CMOS technology. The study of ion channels is needed to model the interface between nanoelectronics and biological cells. Till recently, theoretical analysis of ion transport has been limited to low-resolution continuum diffusion-based or kinetic-based models. Such analytical models fail to include the factors affecting the ionic conduction through ion channels. In this paper, an electro-diffusion model is presented which extends previous models to incorporate the effects of electric field, energy barrier, and rate-limited association/dissociation of ions with protein charges inside the channel. We derive the probability density function (p.d.f.), the correlation function, and the spectral density of ion number fluctuation. ER - TY - JOUR AU - Stelling, Jörg AU - Sauer, Uwe AU - Szallasi, Zoltan AU - Doyle, Francis J. AU - Doyle, John T1 - Robustness of Cellular Functions JO - Cell PY - 2004/10 VL - 118 IS - 6 SP - 675 EP - 685 UR - http://dx.doi.org/10.1016/j.cell.2004.09.008 DO - 10.1016/j.cell.2004.09.008 KW - cells KW - KW - resilience KW - KW - review L1 - SN - N1 - N1 - AB - Robustness, the ability to maintain performance in the face of perturbations and uncertainty, is a long-recognized key property of living systems. Owing to intimate links to cellular complexity, however, its molecular and cellular basis has only recently begun to be understood. Theoretical approaches to complex engineered systems can provide guidelines for investigating cellular robustness because biology and engineering employ a common set of basic mechanisms in different combinations. Robustness may be a key to understanding cellular complexity, elucidating design principles, and fostering closer interactions between experimentation and theory. ER - TY - JOUR AU - Luo, Paifeng AU - Xia, Wei AU - Zhou, Shengwen AU - Sun, Lin AU - Cheng, Jigui AU - Xu, Chenxi AU - Lu, Yingwei T1 - Solvent Engineering for Ambient-Air-Processed, Phase-Stable CsPbI3 in Perovskite Solar Cells JO - The Journal of Physical Chemistry Letters PY - 0/ VL - 0 IS - 0 SP - 3603 EP - 3608 UR - http://dx.doi.org/10.1021/acs.jpclett.6b01576 DO - 10.1021/acs.jpclett.6b01576 KW - Ambient-Air-Processed KW - KW - Cells KW - KW - CsPbI3 KW - KW - Engineering KW - Perovskite KW - Solar KW - Solvent L1 - SN - N1 - N1 - AB - Inorganic CsPbI3 perovskite solar cells (PSCs) owning comparable photovoltaic performance and enhanced thermal stability compared to organic–inorganic hybrid perovskites have attracted enormous interest in the past year. However, it is still a challenge to stabilize the desired black α-CsPbI3 perovskites in ambient air for photovoltaic applications. Herein, sequential solvent engineering including the addition of hydroiodic acid (HI) and subsequent isopropanol (IPA) treatment for fabricating stable and working CsPbI3 PSCs is developed, and a novel low-temperature phase-transition route from new intermediate Cs4PbI6 to stable α-CsPbI3 is also released for the first time. As such, the as-prepared PSCs give a relatively high power conversion efficiency (PCE) of 4.13% (reverse scan), and the steady-state power output of 1.88% is confirmed for the selected cell with an initial PCE of 3.13 To the best of our knowledge, this is the first demonstration of fabricating CsPbI3 inorganic PSCs under fully open-air conditions. ER -