2026-07-02T09:09:23Zhttps://cipf.fundanetsuite.com/FundanetOAI/oai/recolectaoai:cipf.fundanetsuite.com:p11702026-04-06T13:29:27ZpubrevMetabolic fingerprint of insulin resistance in human polymorphonuclear leucocytesPalomino-Schatzlein, MSimo, RHernandez, CCiudin, AMateos-Gregorio, PHernandez-Mijares, APineda-Lucena, AHerance, JRhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1170info:doi:10.1371/journal.pone.0199351PLoS OneISSN: 19326203info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe present study was aimed at determining the metabolic profile of PMNs in obese subjects, and to explore its potential relationship with insulin resistance (IR). To achieve this goal, a pilot clinical study was performed using PMNs from 17 patients with obesity and IR, and 17 lean controls without IR, which was validated in an additional smaller cohort (consisting of 10 patients and 10 controls). PMNs were isolated from peripheral blood and nuclear magnetic resonance was used to perform the metabolomic analysis. A total of 48 metabolites were quantified. The main metabolic change found in PMNs was a significant increase in 2-aminoisobutyric acid with a direct correlation with HOMA-IR (p<0.001), BMI (p<0.000001) and waist circumference (p<0.000001). By contrast, a decrease of 3-hydroxyisovalerate was observed with an inverse correlation with HOMA-IR (p = 0.001), BMI (p = 0.001) and waist circumference (p = 0.0001). Notably, the metabolic profile in plasma was different than that obtained in PMNs. In summary, our results suggest that the change in 3-hydroxyisovalerate and 2-aminoisobutyric is the key metabolic fingerprint in PMNs of obese subjects with IR. In addition, our methodology could be an easy and reliable tool for monitoring the effect of treatments in the setting of precision medicine.PUBLIC LIBRARY SCIENCEenginfo:eu-repo/semantics/restrictedAccess2018-07-13oai:cipf.fundanetsuite.com:p11712026-04-06T13:29:27ZpubrevA Preview of Selected ArticlesAtkinson, SPhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1171info:doi:10.1002/sctm.18-0194Stem Cells Translational MedicineISSN: 21576564ISSNe: 21576580info:eu-repo/semantics/lectureEditorial Materialinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-10-01oai:cipf.fundanetsuite.com:p11722026-03-24T12:10:10ZpubrevPolyacetal-Based Combination Therapy for the Treatment of Prostate CancerPlyduang, TArminan, AEngland, RMWiwattanapatapee, RVicent, MJhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1172info:doi:10.1002/marc.201800265MACROMOLECULAR RAPID COMMUNICATIONSISSN: 10221336ISSNe: 15213927info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe high incidence of prostate carcinogenesis has prompted the search for novel effective treatment approaches. We have employed curcumin (Curc) and diethylstilbestrol (DES) to synthesize a series of polyacetal (PA)-based combination conjugates for prostate cancer (PCa) treatment. Given their bihydroxyl functionalities, Curc and DES molecules were incorporated into a PA mainchain using a one-pot reaction between diols and divinyl ethers. The PA-conjugates released both drugs under acidic conditions, such as those found in the tumor microenvironment, endosomes, or lysosomes, while remaining stable at neutral pH 7.4. The drug ratio was optimized to achieve anticancer drug synergism with elevated cytotoxicity against LNCaP-hormone-dependent human PCa cells conferred via the induction of S phase cell cycle arrest by the upregulation of p53 and CDK inhibitors p21Waf/CIP1 and downregulation of cyclin D1. The application of rationally designed PA-Curc-DES combination conjugates represents a potentially exciting new treatment for prostate cancer.combination therapy; curcumin; diethylstilbestrol; polyacetals; prostate cancerWILEY-V C H VERLAG GMBHenginfo:eu-repo/semantics/restrictedAccess2018-10-01oai:cipf.fundanetsuite.com:p11732026-04-06T13:29:27ZpubrevUrea cycle dysregulation in non-alcoholic fatty liver diseaseDe Chiara, FHeeboll, SMarrone, GMontoliu, CHamilton-Dutoit, SFerrandez, AAndreola, FRombouts, KGronbaek, HFelipo, VGracia-Sancho, JMookerjee, RPVilstrup, HJalan, RThomsen, KLhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1173info:doi:10.1016/j.jhep.2018.06.023JOURNAL OF HEPATOLOGYISSN: 01688278ISSNe: 16000641info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionBackground & Aims: In non-alcoholic steatohepatitis (NASH), the function of urea cycle enzymes (UCEs) may be affected, resulting in hyperammonemia and the risk of disease progression. We aimed to determine whether the expression and function of UCEs are altered in an animal model of NASH and in patients with non-alcoholic fatty liver disease (NAFLD), and whether this process is reversible.
Methods: Rats were first fed a high-fat, high-cholesterol diet for 10 months to induce NASH, before being switched onto a normal chow diet to recover. In humans, we obtained liver biopsies from 20 patients with steatosis and 15 with NASH. Primary rat hepatocytes were isolated and cultured with free fatty acids. We measured the gene and protein expression of ornithine transcarbamylase (OTC) and carbamoylphosphate synthetase (CPS1), as well as OTC activity, and ammonia concentrations. Moreover, we assessed the promoter methylation status of OTC and CPS1 in rats, humans and steatotic hepatocytes.
Results: In NASH animals, gene and protein expression of OTC and CPS1, and the activity of OTC, were reversibly reduced. Hypermethylation of Otc promoter genes was also observed. Additionally, in patients with NAFLD, OTC enzyme concentration and activity were reduced and ammonia concentrations were increased, which was further exacerbated in those with NASH. Furthermore, OTC and CPS1 promoter regions were hypermethylated. In primary hepatocytes, induction of steatosis was associated with Otc promoter hypermethylation, a reduction in the gene expression of Otc and Cps1, and an increase in ammonia concentration in the supernatant.
Conclusion: NASH is associated with a reduction in the gene and protein expression, and activity, of UCEs. This results in hyperammonemia, possibly through hypermethylation of UCE genes and impairment of urea synthesis. Our investigations are the first to describe a link between NASH, the function of UCEs, and hyperammonemia, providing a novel therapeutic target.
Lay summary: In patients with fatty liver disease, the enzymes that convert nitrogen waste into urea may be affected, leading to the accumulation of ammonia, which is toxic. This accumulation of ammonia can lead to scar tissue development, increasing the risk of disease progression. In this study, we show that fat accumulation in the liver produces a reversible reduction in the function of the enzymes that are involved in detoxification of ammonia. These data provide potential new targets for the treatment of fatty liver disease. (C) 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.ELSEVIERenginfo:eu-repo/semantics/restrictedAccess2018-10-01oai:cipf.fundanetsuite.com:p11742026-03-24T12:10:10ZpubrevCombined plasma rich in growth factors and adipose-derived mesenchymal stem cells promotes the cutaneous wound healing in rabbitsChicharro, DCarrillo, JMRubio, MCugat, RCuervo, BGuil, SForteza, JMoreno, VVilar, JMSopena, Jhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1174info:doi:10.1186/s12917-018-1577-yBMC Veterinary ResearchISSN: 17466148info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionBackground: The use of Plasma Rich in Growth Factors (PRGF) and Adipose Derived Mesenchymal Stem Cells (ASCs) are today extensively studied in the field of regenerative medicine. In recent years, human and veterinary medicine prefer to avoid using traumatic techniques and choose low or non-invasive procedures. The objective of this study was to evaluate the efficacy of PRGF, ASCs and the combination of both in wound healing of full-thickness skin defects in rabbits. With this purpose, a total of 144 rabbits were used for this study. The animals were divided in three study groups of 48 rabbits each depending on the administered treatment: PRGF, ASCs, and PGRF+ASCs. Two wounds of 8 mm of diameter and separated from each other by 20 mm were created on the back of each rabbit the first was treated with saline solution, and the second with the treatment assigned for each group. Macroscopic and microscopic evolution of wounds was assessed at 1, 2, 3, 5, 7 and 10 days post-surgery. With this aim, 8 animals from each treatment group and at each study time were euthanized to collect wounds for histopathological study.
Results: Wounds treated with PRGF, ASCs and PRGF+ASCs showed significant higher wound healing and epithelialization rates, more natural aesthetic appearance, significant lower inflammatory response, significant higher collagen deposition and angiogenesis compared with control wounds. The combined treatment PRGF+ASCs showed a significant faster cutaneous wound healing process.
Conclusions: The combined treatment PRGF+ASCs showed the best results, suggesting this is the best choice to enhance wound healing and improve aesthetic results in acute wounds.Adipose-derived mesenchymal stem cells (ASCs); Plasma rich in growth factors (PRGF); Wound healing; Rabbits; Skin; Regenerative medicine; Growth factorsBMCenginfo:eu-repo/semantics/restrictedAccess2018-09-21oai:cipf.fundanetsuite.com:p11752026-04-06T13:29:27ZpubrevIn Vivo Imaging of MMP-13 Activity Using a Specific Polymer-FRET Peptide Conjugate Detects Early Osteoarthritis and Inhibitor EfficacyLim, NHTranchant, IAmoura, MBeau, FWieland, HKingler, OHerrmann, MNazare, MPlettenburg, ODive, VVicent, MJNagase, Hhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1175info:doi:10.1002/adfm.201802738ADVANCED FUNCTIONAL MATERIALSISSN: 1616301XISSNe: 16163028info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionImaging early molecular changes in osteoarthritic (OA) joints is instrumental for the development of disease-modifying drugs. To this end, a fluorescent resonance energy transfer-based peptide probe that is cleavable by matrix metalloproteinase 13 (MMP-13) has been developed. This protease degrades type II collagen, a major matrix component of cartilage. The probe exhibits high catalytic efficiency (k(cat)/K-M = 6.5 x 10(5) m(-1) s(-1)) and high selectivity for MMP-13 over a set of nine MMPs. To achieve optimal in vivo pharmacokinetics and tissue penetration, the probe has been further conjugated to a linear l-polyglutamate chain of 30 kDa. The conjugate detects early biochemical events that occur in a surgically induced murine model of OA before major histological changes. The nanometric probe is suitable for the monitoring of in vivo efficacy of an orally bioavailable MMP-13 inhibitor, which effectively blocks cartilage degradation during the development of OA. This new polymer-probe can therefore be a useful tool in detecting early OA, disease progression, and in developing MMP-13-based disease-modifying drugs for OA.early detection; live imaging; MMP-13 nanoprobes; osteoarthritis; polymer therapeuticsWILEY-V C H VERLAG GMBHenginfo:eu-repo/semantics/restrictedAccess2018-09-12oai:cipf.fundanetsuite.com:p11762026-04-06T13:29:27ZpubrevRecent advances in the synthesis of functionalised monofluorinated compoundsFustero, SSedgwick, DMRoman, RBarrio, Phttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1176info:doi:10.1039/c8cc05181jCHEMICAL COMMUNICATIONSISSN: 13597345ISSNe: 1364548Xinfo:eu-repo/semantics/reviewinfo:eu-repo/semantics/publishedVersionOver the past few years, we have tackled the synthesis of interesting monofluorinated organic molecules, such as: dihydronaphthalene derivatives, beta-fluoro sulfones and related carbonyl compounds, fluorohydrins and allylic alcohols. Overall, a wide range of modern synthetic techniques are covered in this feature article including transition-metal, photo- and organocatalysis, nucleophilic and electrophilic fluorinations, chiral auxiliaries and enantioselective catalysis.ROYAL SOC CHEMISTRYenginfo:eu-repo/semantics/restrictedAccess2018-09-11oai:cipf.fundanetsuite.com:p11772026-04-06T13:29:27ZpubrevA Preview of Selected ArticlesAtkinson, SPhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1177info:doi:10.1002/sctm.18-0158Stem Cells Translational MedicineISSN: 21576564ISSNe: 21576580info:eu-repo/semantics/reviewinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-09-01oai:cipf.fundanetsuite.com:p11802026-03-24T12:10:10ZpubrevAn Alternative Homodimerization Interface of MnmG Reveals a Conformational Dynamics that Is Essential for Its tRNA Modification FunctionRuiz-Partida, RPrado, SVillarroya, MVelazquez-Campoy, ABravo, JArmengod, MEhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1180info:doi:10.1016/j.jmb.2018.05.035JOURNAL OF MOLECULAR BIOLOGYISSN: 00222836ISSNe: 10898638info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe Escherichia coli homodimeric proteins MnmE and MnmG form a functional complex, MnmEG, that modifies tRNAs using GTP, methylene-tetrahydrofolate, FAD, and glycine or ammonium. MnmE is a tetrahydrofolate- and GTP-binding protein, whereas MnmG is a FAD-binding protein with each protomer composed of the FAD-binding domain, two insertion domains, and the helical C-terminal domain. The detailed mechanism of the MnmEG-mediated reaction remains unclear partially due to incomplete structural information on the free- and substrate-bound forms of the complex. In this study, we show that MnmG can adopt in solution a dimer arrangement (form I) different from that currently considered as the only biologically active (form II). Normal mode analysis indicates that form I can oscillate in a range of open and closed conformations. Using isothermal titration calorimetry and native red electrophoresis, we show that a form-I open conformation, which can be stabilized in vitro by the formation of an interprotomer disulfide bond between the catalytic C277 residues, appears to be involved in the assembly of the MnmEG catalytic center. We also show that residues R196, D253, R436, R554 and E585 are important for the stabilization of form I and the tRNA modification function. We propose that the form I dynamics regulates the alternative access of MnmE and tRNA to the MnmG FAD active site. Finally, we show that the C-terminal region of MnmG contains a sterile alpha motif domain responsible for tRNA-protein and protein-protein interactions. (C) 2018 The Authors. Published by Elsevier Ltd.flavoenzymes; interprotomer disulfide bridges; MnmE; MTO1; sterile alpha motifACADEMIC PRESS LTD- ELSEVIER SCIENCE LTDenginfo:eu-repo/semantics/restrictedAccess2018-08-17oai:cipf.fundanetsuite.com:p11812026-04-06T13:29:27ZpubrevHybrid Mesoporous Nanocarriers Act by Processing Logic Tasks: Toward the Design of Nanobots Capable of Reading Information from the EnvironmentLlopis-Lorente, Ade Luis, BGarcia-Fernandez, AJimenez-Falcao, SOrzaez, MSancenon, FVillalonga, RMartinez-Manez, Rhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1181info:doi:10.1021/acsami.8b05920ACS Applied Materials & InterfacesISSN: 19448244ISSNe: 19448252info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionHere, we present the design of smart nano-devices capable of reading molecular information from the environment and acting accordingly by processing Boolean logic tasks. As proof of concept, we prepared Au-mesoporous silica (MS) nanoparticles functionalized with the enzyme glucose dehydrogenase (GDH) on the Au surface and with supramolecular nanovalves as caps on the MS surface, which is loaded with a cargo (dye or drug). The nanodevice acts as an AND logic gate and reads information from the solution (presence of glucose and nicotinamide adenine dinucleotide (NADI), which results in cargo release. We show the possibility of coimmobilizing GDH and the enzyme urease on nanoparticles to mimic an INHIBIT logic gate, in which the AND gate is switched off by the presence of urea. We also show that such nanodevices can deliver cytotoxic drugs in cancer cells by recognizing intracellular NAD(+) and the presence of glucose.biocomputing; nanorobots; logic gates; mesoporous nanoparticles; drug deliveryAMER CHEMICAL SOCenginfo:eu-repo/semantics/restrictedAccess2018-08-08oai:cipf.fundanetsuite.com:p11822026-03-24T12:10:10ZpubrevDual Role of Vinyl Sulfonamides as N-Nucleophiles and Michael Acceptors in the Enantioselective Synthesis of Bicyclic delta-SultamsMulet, CEscolano, MLlopis, SSanz, Sde Arellano, CRFustero, Sdel Pozo, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1182info:doi:10.1002/adsc.201800548ADVANCED SYNTHESIS & CATALYSISISSN: 16154150ISSNe: 16154169info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionA new methodology for the synthesis of enantiomerically enriched bicyclic delta-sultams is described, involving an initial organocatalytic intramolecular aza-Michael reaction of vinyl sulfonamides bearing a conjugated ketone at a remote position. The resulting Michael adducts were then subjected to an intramolecular conjugate addition over the vinyl sulfone moiety, thus rendering the final bicyclic sultams containing two stereocenters. The key point of this strategy relies on the use of vinyl sulfonamides as both, nitrogen nucleophiles and Michael acceptors. The use of phosphazene-derived bases avoided the racemization of the intermediate derivatives, rendering 6-membered ring bicyclic delta-sultams in enantiomerically enriched manner with a small erosion of enantiopurity. Anyway, after recrystallization, final sultams were obtained in almost enantiomerically pure form. Nevertheless, the enantioselective synthesis of either 5-membered ring products or benzofused derivatives was found to be out of the scope of our strategy.vinyl sulfonamides; intramolecular Michael addition; bicyclic sultams; enantioselectivity; organocatalysisWILEY-V C H VERLAG GMBHenginfo:eu-repo/semantics/restrictedAccess2018-08-06oai:cipf.fundanetsuite.com:p11832026-04-06T13:29:27ZpubrevGeneration of a human iPSC line from a patient with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) caused by mutation in SACSIN geneMACHUCA, C.Vilches, AClemente, EPascual-Pascual, SIBolinches-Amoros, ACastro, AAESPINÓS, C.Rodriguez, MLJendelova, PERCEG, S.https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1183info:doi:10.1016/j.scr.2018.07.012Stem Cell ResearchISSN: 18735061ISSNe: 18767753info:eu-repo/semantics/lectureEditorial Materialinfo:eu-repo/semantics/publishedVersionThe human iPSC cell line, ARS-FiPS4F1 (ESi063-A), derived from dermal fibroblast from the patient autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) caused by mutations on the gene SACSIN, was generated by non-integrative reprogramming technology using OCT3/4, SOX2, CMYC and KLF4 reprogramming factors. The pluripotency was assessed by immunocytochemistry and RT-PCR. Differentiation capacity was verified in vitro. This iPSC line can be further differentiated toward affected cells to better understand molecular mechanisms of disease and pathophysiology.ELSEVIERenginfo:eu-repo/semantics/openAccess2018-08-01oai:cipf.fundanetsuite.com:p11842026-06-23T03:23:12ZpubrevUse of Medaka Fish as Vertebrate Model to Study the Effect of Cocoa Polyphenols in the Resistance to Oxidative Stress and Life Span ExtensionSanchez-Sanchez, AVLeal-Tassias, ARodriguez-Sanchez, NPiquer-Gil, MMartorell, PGenoves, SAcosta, CBurks, DRamon, DMullor, JLhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1184info:doi:10.1089/rej.2017.1982REJUVENATION RESEARCHISSN: 15491684ISSNe: 15578577info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionOxidative stress (OS) can induce cell apoptosis and thus plays an important role in aging. Antioxidant foods protect tissues from OS and contribute to a healthier lifestyle. In this study, we described the used of medaka embryos (Oryzias latipes) to study the putative antioxidant capacity of dietary cocoa extract in vertebrates. A polyphenol-enriched cocoa extract regulated the expression of several genes implicated in OS, thereby protecting fish embryos from induced OS. The cocoa extract activated superoxide dismutase enzyme activity in embryos and adult fish tissues, suggesting a common mechanism for protection during embryonic development and adulthood. Furthermore, long-term feeding of the cocoa extract increased fish life span. Our study demonstrates that the polyphenol-enriched cocoa extract decreases OS and extends life span in medaka fish, validating the use of medaka embryos as an economical platform to screen the antioxidant capacity of food compounds.medaka fish; cocoa polyphenols; antioxidant; life span extension; Sod; FoxOSAGE PUBLICATIONS INCenginfo:eu-repo/semantics/restrictedAccess2018-08-01oai:cipf.fundanetsuite.com:p11852026-04-06T13:29:27ZpubrevA Preview of Selected Articles - August 2018Atkinson, SPhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1185info:doi:10.1002/stem.2867STEM CELLSISSN: 10665099ISSNe: 15494918info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-08-01oai:cipf.fundanetsuite.com:p11862026-03-24T12:10:10ZpubrevTranscriptome analysis reveals novel insights into the response of low-dose benzo(a)pyrene exposure in male tilapiaColli-Dula, RCFang, XMoraga-Amador, DAlbornoz-Abud, NZamora-Bustillos, RConesa, AZapata-Perez, OMoreno, DHernandez-Nunez, Ehttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1186info:doi:10.1016/j.aquatox.2018.06.005AQUATIC TOXICOLOGYISSN: 0166445XISSNe: 18791514info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionDespite a wide number of toxicological studies that describe benzo[a]pyrene (BaP) effects, the metabolic mechanisms that underlie these effects in fish are largely unknown. Of great concern is the presence of BaP in aquatic systems, especially those in close proximity to human activity leading to consumption of potentially contaminated foods. BaP is a known carcinogen and it has been reported to have adverse effects on the survival, development and reproduction of fish. The purpose of this study was to investigate if a low dose of BaP can alter genes and key metabolic pathways in the liver and testis in male adult tilapia, and whether these could be associated with biological endpoints disruption. We used both high-throughput RNA-Sequencing to assess whole genome gene expression following repeated intraperitoneal injections of 3 mg/kg of BaP (every 6 days for 26 days) and morphometric endpoints as indicators of general health. Condition factor (K) along with hepatosomatic and gonadosomatic indices (morphometric parameters) were significantly lower in BaP-treated fish than in controls. BaP exposure induced important changes in the gene expression pattern in liver and testis as revealed by both Pathway and Gene Ontology (GO) analyses. Alterations that were shared by both tissues included arachidonic acid metabolism, androgen receptor to prostate-specific antigen signaling, and insulin-associated effects on lipogenesis. The most salient liver-specific effects included: biological processes involved in detoxification, IL6-associated insulin resistance, mTOR hyperactivation, mitotic cytokinesis, spindle pole and microtubule binding. BaP effects that were confined to the testis included: immune system functions, inflammatory response, estrogen and androgen metabolic pathways. Taken together, gene expression and morphometric end point data indicate that the reproductive success of adult male tilapia could be compromised as a result of BaP exposure. These results constitute new insights on the mechanism of action of low dose BaP in a non-model organism (tilapia).Benzo(a)pyrene; Tilapia; Transcriptomics; RNA-SeqELSEVIERenginfo:eu-repo/semantics/restrictedAccess2018-08-01oai:cipf.fundanetsuite.com:p11872026-04-06T13:29:27ZpubrevPaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics dataHernandez-de-Diego, RTarazona, SMartinez-Mira, CBalzano-Nogueira, LFurio-Tari, PPappas, GJConesa, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1187info:doi:10.1093/nar/gky466NUCLEIC ACIDS RESEARCHISSN: 03051048ISSNe: 13624962info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe increasing availability of multi-omic platforms poses new challenges to data analysis. Joint visualization of multi-omics data is instrumental in better understanding interconnections across molecular layers and in fully utilizing the multi-omic resources available to make biological discoveries. We present here PaintOmics 3, a web-based resource for the integrated visualization of multiple omic data types onto KEGG pathway diagrams. PaintOmics 3 combines server-end capabilities for data analysis with the potential of modern web resources for data visualization, providing researchers with a powerful framework for interactive exploration of their multi-omics information. Unlike other visualization tools, PaintOmics 3 covers a comprehensive pathway analysis workflow, including automatic feature name/identifier conversion, multi-layered feature matching, pathway enrichment, network analysis, interactive heatmaps, trend charts, and more. It accepts a wide variety of omic types, including transcriptomics, proteomics and metabolomics, as well as region-based approaches such as ATAC-seq or ChIP-seq data. The tool is freely available at www.paintomics.orgOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-07-02oai:cipf.fundanetsuite.com:p11882026-04-06T13:29:27ZpubrevA Preview of Selected ArticlesAtkinson, SPhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1188info:doi:10.1002/sctm.18-0110Stem Cells Translational MedicineISSN: 21576564ISSNe: 21576580info:eu-repo/semantics/lectureEditorial Materialinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-07-01oai:cipf.fundanetsuite.com:p11892026-03-24T12:10:10ZpubrevStructural understanding of nitrogen signaling in cyanobacteria via global nitrogen regulator NtcA and protein PipXForcada-Nadal, ALlacer, JLPalomino-Schatzlein, MNeira, JLPineda-Lucena, AContreras, ARubio, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1189FEBS Open BioISSN: 22115463info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionWILEYenginfo:eu-repo/semantics/restrictedAccess2018-07-01oai:cipf.fundanetsuite.com:p11902026-03-24T12:10:10ZpubrevMetabolic profile analysis of a Drosophila model of Parkinson's diseaseLopez, FJSManrique, CSSoriano, VMSchatzlein, MPLucena, APParicio, Nhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1190FEBS Open BioISSN: 22115463info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionWILEYenginfo:eu-repo/semantics/restrictedAccess2018-07-01oai:cipf.fundanetsuite.com:p11912026-04-06T13:29:27ZpubrevLearning and Memory Impairments in Patients with Minimal Hepatic Encephalopathy are Associated with Structural and Functional Connectivity Alterations in HippocampusGarcia-Garcia, RCruz-Gomez, AJUrios, AMangas-Losada, AForn, CEscudero-Garcia, DKosenko, ETorregrosa, ITosca, JGiner-Duran, RSerra, MAAvila, CBelloch, VFelipo, VMontoliu, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1191info:doi:10.1038/s41598-018-27978-xScientific ReportsISSN: 20452322info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPatients with minimal hepatic encephalopathy (MHE) show mild cognitive impairment associated with alterations in attentional and executive networks. There are no studies evaluating the relationship between memory in MHE and structural and functional connectivity (FC) changes in the hippocampal system. This study aimed to evaluate verbal learning and long-term memory in cirrhotic patients with (C-MHE) and without MHE (C-NMHE) and healthy controls. We assessed the relationship between alterations in memory and the structural integrity and FC of the hippocampal system. C-MHE patients showed impairments in learning, long-term memory, and recognition, compared to C-NMHE patients and controls. Cirrhotic patients showed reduced fimbria volume compared to controls. Larger volumes in hippocampus subfields were related to better memory performance in C-NMHE patients and controls. C-MHE patients presented lower FC between the L-presubiculum and L-precuneus than C-NMHE patients. Compared to controls, C-MHE patients had reduced FC between L-presubiculum and subiculum seeds and bilateral precuneus, which correlated with cognitive impairment and memory performance. Alterations in the FC of the hippocampal system could contribute to learning and longterm memory impairments in C-MHE patients. This study demonstrates the association between alterations in learning and long-term memory and structural and FC disturbances in hippocampal structures in cirrhotic patients.NATURE PORTFOLIOenginfo:eu-repo/semantics/restrictedAccess2018-06-25oai:cipf.fundanetsuite.com:p11922026-04-06T13:29:27ZpubrevBMP and WNT signalling cooperate through LEF1 in the neuronal specification of adult hippocampal neural stem and progenitor cellsArmenteros, TAndreu, ZHortiguela, RLie, DCMira, Hhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1192info:doi:10.1038/s41598-018-27581-0Scientific ReportsISSN: 20452322info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionNeuronal production from neural stem cells persists during adulthood in the subgranular zone of the hippocampal dentate gyrus. Extracellular signals provided by the hippocampal microenvironment regulate the neuronal fate commitment of the stem cell progeny. To date, the identity of those signals and their crosstalk has been only partially resolved. Here we show that adult rat hippocampal neural stem and progenitor cells (AH-NSPCs) express receptors for bone morphogenetic proteins (BMPs) and that the BMP/P-Smad pathway is active in AH-NSPCs undergoing differentiation towards the neuronal lineage. In vitro, exposure to the BMP2 and BMP4 ligands is sufficient to increase neurogenesis from AH-NSPCs in a WNT dependent manner while decreasing oligodendrogenesis. Moreover, BMP2/4 and WNT3A, a key regulator of adult hippocampal neurogenesis, cooperate to further enhance neuronal production. Our data point to a mechanistic convergence of the BMP and WNT pathways at the level of the T-cell factor/lymphoid enhancer factor gene Lef1. Altogether, we provide evidence that BMP signalling is an important regulator for the neuronal fate specification of AH-NSPCs cultures and we show that it significantly cooperates with the previously described master regulator of adult hippocampal neurogenesis, the WNT signalling pathway.NATURE PORTFOLIOenginfo:eu-repo/semantics/restrictedAccess2018-06-18oai:cipf.fundanetsuite.com:p11932026-03-24T12:10:10ZpubrevEvidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in PneumocystisDelaye, LRuiz-Ruiz, SCalderon, ETarazona, SConesa, AMoya, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1193info:doi:10.1093/gbe/evy116Genome Biology and EvolutionISSN: 17596653info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPneumocystis species are ascomycete fungi adapted to live inside the lungs of mammals. These ascomycetes show extensive stenoxenism, meaning that each species of Pneumocystis infects a single species of host. Here, we study the effect exerted by natural selection on gene evolution in the genomes of three Pneumocystis species. We show that genes involved in host interaction evolve under positive selection. In the first place, we found strong evidence of episodic diversifying selection in Major surface glycoproteins (Msg). These proteins are located on the surface of Pneumocystis and are used for host attachment and probably for immune system evasion. Consistent with their function as antigens, most sites under diversifying selection in Msg code for residues with large relative surface accessibility areas. We also found evidence of positive selection in part of the cell machinery used to export Msg to the cell surface. Specifically, we found that genes participating in glycosylphosphatidylinositol (GPI) biosynthesis show an increased rate of nonsynonymous substitutions (dN) versus synonymous substitutions (dS). GPI is a molecule synthesized in the endoplasmic reticulum that is used to anchor proteins to membranes. We interpret the aforementioned findings as evidence of selective pressure exerted by the host immune system on Pneumocystis species, shaping the evolution of Msg and several proteins involved in GPI biosynthesis. We suggest that genome evolution in Pneumocystis is well described by the Red-Queen hypothesis whereby genes relevant for biotic interactions show accelerated rates of evolution.stenoxenism; majors surface glycoproteins; glycosylphosphatidylinositol; natural selectionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-06-01oai:cipf.fundanetsuite.com:p11942026-04-06T13:29:27ZpubrevBioengineering Approaches for Bladder RegenerationSerrano-Aroca, AVera-Donoso, CDMoreno-Manzano, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1194info:doi:10.3390/ijms19061796INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 14220067info:eu-repo/semantics/reviewinfo:eu-repo/semantics/publishedVersionCurrent clinical strategies for bladder reconstruction or substitution are associated to serious problems. Therefore, new alternative approaches are becoming more and more necessary. The purpose of this work is to review the state of the art of the current bioengineering advances and obstacles reported in bladder regeneration. Tissue bladder engineering requires an ideal engineered bladder scaffold composed of a biocompatible material suitable to sustain the mechanical forces necessary for bladder filling and emptying. In addition, an engineered bladder needs to reconstruct a compliant muscular wall and a highly specialized urothelium, well-orchestrated under control of autonomic and sensory innervations. Bioreactors play a very important role allowing cell growth and specialization into a tissue-engineered vascular construct within a physiological environment. Bioprinting technology is rapidly progressing, achieving the generation of custom-made structural supports using an increasing number of different polymers as ink with a high capacity of reproducibility. Although many promising results have been achieved, few of them have been tested with clinical success. This lack of satisfactory applications is a good reason to discourage researchers in this field and explains, somehow, the limited high-impact scientific production in this area during the last decade, emphasizing that still much more progress is required before bioengineered bladders become a commonplace in the clinical setting.bladder regeneration; bioreactors; c; regenerative medicine; stem cells; scaffoldsMDPIenginfo:eu-repo/semantics/restrictedAccess2018-06-01oai:cipf.fundanetsuite.com:p11952026-04-06T13:29:27ZpubrevDegradation of altered mitochondria by autophagy is impaired in Lafora diseaseLahuerta, MAguado, CSanchez-Martin, PSanz, PKnecht, Ehttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1195info:doi:10.1111/febs.14468FEBS JournalISSN: 1742464XISSNe: 17424658info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionLafora disease (LD) is a fatal neurodegenerative disorder caused mostly by mutations in either of two genes encoding laforin and malin. LD is characterized by accumulation of a poorly branched form of glycogen in the cytoplasm of neurons and other cells. We previously reported dysfunctional mitochondria in different LD models. Now, using mitochondrial uncouplers and respiratory chain inhibitors, we have investigated with human fibroblasts a possible alteration in the selective degradation of damaged mitochondria (mitophagy) in LD. By flow cytometry of MitoTracker-labelled cells and measuring the levels of various mitochondrial proteins by western blot, we found in LD fibroblasts a partial impairment in the increased mitochondrial degradation produced by these treatments. In addition, colocalization of mitochondrial and lysosomal markers decreased in LD fibroblasts. All these results are consistent with a partial impairment in the induced autophagic degradation of dysfunctional mitochondria in LD fibroblasts. However, canonical recruitment of Parkin to mitochondria under these conditions remained unaffected in LD fibroblasts, and also in SH-SY5Y cells after malin and laforin overexpression. Neither mitochondrial localization nor protein levels of Bcl-2-like protein 13, another component of the mitophagic machinery that operates under these conditions, were affected in LD fibroblasts. In contrast, although these treatments raised autophagy in both control and LD fibroblasts, this enhanced autophagy was clearly lower in the latter cells. Therefore, the autophagic degradation of altered mitochondria is impaired in LD, which is due to a partial defect in the autophagic response and not in the canonical mitophagy signalling pathways.autophagy; human fibroblasts; Lafora disease; mitochondria; mitophagyWILEYenginfo:eu-repo/semantics/restrictedAccess2018-06-01oai:cipf.fundanetsuite.com:p11962026-04-06T13:29:27ZpubrevA Preview of Selected Articles - June 2018Atkinson, SPhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1196info:doi:10.1002/stem.2841STEM CELLSISSN: 10665099ISSNe: 15494918info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-06-01oai:cipf.fundanetsuite.com:p11972026-04-06T13:29:27ZpubrevInhibition of gamma-Secretase Leads to an Increase in Presenilin-1Sogorb-Esteve, AGarcia-Ayllon, MSLlansola, MFelipo, VBlennow, KSaez-Valero, Jhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1197info:doi:10.1007/s12035-017-0705-1MOLECULAR NEUROBIOLOGYISSN: 08937648ISSNe: 15591182info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiongamma-Secretase inhibitors (GSIs) are potential therapeutic agents for Alzheimer's disease (AD); however, trials have proven disappointing. We addressed the possibility that gamma-secretase inhibition can provoke a rebound effect, elevating the levels of the catalytic gamma-secretase subunit, presenilin-1 (PS1). Acute treatment of SH-SY5Y cells with the GSI LY-374973 (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, DAPT) augments PS1, in parallel with increases in other gamma-secretase subunits nicastrin, presenilin enhancer 2, and anterior pharynx-defective 1, yet with no increase in messenger RNA expression. Over-expression of the C-terminal fragment (CTF) of APP, C99, also triggered an increase in PS1. Similar increases in PS1 were evident in primary neurons treated repeatedly (4 days) with DAPT or with the GSI BMS-708163 (avagacestat). Likewise, rats examined after 21 days administered with avagacestat (40 mg/kg/day) had more brain PS1. Sustained gamma-secretase inhibition did not exert a long-term effect on PS1 activity, evident through the decrease in CTFs of APP and ApoER2. Prolonged avagacestat treatment of rats produced a subtle impairment in anxiety-like behavior. The rebound increase in PS1 in response to GSIs must be taken into consideration for future drug development.Alzheimer's disease; Presenilin-1; gamma-Secretase inhibitor; TherapySPRINGERenginfo:eu-repo/semantics/restrictedAccess2018-06-01oai:cipf.fundanetsuite.com:p11982026-04-06T13:29:27ZpubrevAnticancer Activity Driven by Drug Linker Modification in a Polyglutamic Acid-Based Combination-Drug ConjugateArroyo-Crespo, JJNebot, VJCharbonnier, DMasia, EPaul, AJames, CArminan, AVicent, MJhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1198info:doi:10.1002/adfm.201800931ADVANCED FUNCTIONAL MATERIALSISSN: 1616301XISSNe: 16163028info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionCombination nanotherapies for the treatment of breast cancer permits synergistic drug targeting of multiple pathways. However, poor carrier degradability, poor synergism of the combined drugs, low drug release regulation, and a lack of control on final macromolecule solution conformation (which drives the biological fate) limit the application of this strategy. The present study describes the development of a family of drug delivery systems composed of chemotherapeutic (doxorubicin) and endocrine therapy (aromatase inhibitor aminoglutethimide) agents conjugated to a biodegradable poly-l-glutamic acid backbone via various linking moieties. Data from in vitro cytotoxicity and drug release assessments and animal model validation select a conjugate family member with optimal biological performance. Exhaustive physicochemical characterization in relevant media (including the study of secondary structure, size measurements, and detailed small-angle neutron scattering analysis) correlates biological data with the intrinsic supramolecular characteristics of the conjugate. Overall, this study demonstrates how a small flexible Gly linker can modify the spatial conformation of the entire polymer-drug conjugate, promote the synergistic release of both drugs, and significantly improve biological activity. These findings highlight the need for a deeper understanding of polymer-drug conjugates at supramolecular level to allow the design of more effective polymer-drug conjugates.breast cancer; combination therapy; polymer therapeutics; polymer-drug conjugates; polypeptidesWILEY-V C H VERLAG GMBHenginfo:eu-repo/semantics/openAccess2018-05-30oai:cipf.fundanetsuite.com:p11992026-04-06T13:29:27ZpubrevANKK1 is found in myogenic precursors and muscle fibers subtypes with glycolytic metabolismRubio-Solsona, EMarti, SVilchez, JJPalau, Fhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1199info:doi:10.1371/journal.pone.0197254PLoS OneISSN: 19326203info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAnkyrin repeat and kinase domain containing 1 (ANKK1) gene has been widely related to neuropsychiatry disorders. The localization of ANKK1 in neural progenitors and its correlation with the cell cycle has suggested its participation in development. However, ANKK1 functions still need to be identified. Here, we have further characterized the ANKK1 localization in vivo and in vitro, by using immunolabeling, quantitative real-time PCR and Western blot in the myogenic lineage. Histologic investigations in mice and humans revealed that ANKK1 is expressed in precursors of embryonic and adult muscles. In mice embryos, ANKK1 was found in migrating myotubes where it shows a polarized cytoplasmic distribution, while proliferative myoblasts and satellite cells show different isoforms in their nuclei and cytoplasm. In vitro studies of ANKK1 protein isoforms along the myogenic progression showed the decline of nuclear ANKK1-kinase until its total exclusion in myotubes. In adult mice, ANKK1 was expressed exclusively in the Fast-Twitch muscles fibers subtype. The induction of glycolytic metabolism in C2C12 cells with high glucose concentration or treatment with berberine caused a significant increase in the ANKK1 mRNA. Similarly, C2C12 cells under hypoxic conditions caused the increase of nuclear ANKK1. These results altogether show a relationship between ANKK1 gene regulation and the metabolism of muscles during development and in adulthood. Finally, we found ANKK1 expression in regenerative fibers of muscles from dystrophic patients. Future studies in ANKK1 biology and the pathological response of muscles will reveal whether this protein is a novel muscle disease biomarker.PUBLIC LIBRARY SCIENCEenginfo:eu-repo/semantics/restrictedAccess2018-05-14oai:cipf.fundanetsuite.com:p12002026-03-24T12:10:10ZpubrevOsteopontin-deficient progenitor cells display enhanced differentiation to adipocytesMoreno-Viedma, VTardelli, MZeyda, MSibilia, MBurks, JDStulnig, TMhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1200info:doi:10.1016/j.orcp.2018.02.006Obesity Research & Clinical PracticeISSN: 1871403XISSNe: 18780318info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionObjective: Osteopontin (OPN, Spp1) is a protein upregulated in white adipose tissue (WAT) of obese subjects. Deletion of OPN protects mice from high-fat diet-induced WAT inflammation and insulin resistance. However, the alterations mediated by loss of OPN in WAT before the obesogenic challenge have not yet been investigated. Therefore, we hypothesised that the lack of OPN might enhance the pro-adipogenic micro environment before obesity driven inflammation.
Methods: OPN deficiency was tested in visceral (V) and subcutaneous (SC) WAT from WT and Spp1(-/- )female mice. Gene expression for hypoxia, inflammation and adipogenesis was checked in WT vs. Spp1(-/- )mice (n =15). Adipocytes progenitor cells (APC) were isolated by fluorescence cell sorting and role of OPN deficiency in adipogenesis was investigated by cell images and RT-PCR.
Results: We show that Spp1(-/-) maintained normal body and fat-pad weights, although hypoxia and inflammation markers were significantly reduced. In contrast, expression of genes involved in adipogenesis was increased in WAT from Spp1(-/-) mice. Strikingly, APC from Spp1(-/-) were diminished but differentiated more efficiently to adipocytes than those from control mice.
Conclusions: APC from SC-WAT of lean OPN-deficient mice display an enhanced capacity for differentiating to adipocytes. These alterations may explain the healthy expansion of WAT in the OPN-deficient model which is associated with reduced inflammation and insulin resistance. (C) 2018 Published by Elsevier Ltd on behalf of Asia Oceania Association for the Study of Obesity.OPN; Adipose tissue; Inflammation; Insulin resistance; Adipocyte progenitorsELSEVIER SCI LTDenginfo:eu-repo/semantics/restrictedAccess2018-05-01oai:cipf.fundanetsuite.com:p12012026-03-24T12:10:10ZpubrevApoptotic effect as biomarker of disease, severity and follow-up in interstitial cystitisDi Capua-Sacoto, CSanchez-Llopis, AOconnor, JEMartinez-Romero, ARuiz-Cerda, JLhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1201info:doi:10.1016/j.acuro.2017.09.007Actas Urologicas EspanolasISSN: 02104806ISSNe: 16997980info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionObjective: To determine whether the apoptotic effect test could serve as a biomarker of severity in bladder pain syndrome/interstitial cystitis.
Material and methods: A prospective study was conducted between January 2010 and January 2015, which included 57 patients diagnosed with interstitial cystitis and 49 diagnosed with chronic pelvic pain of gynaecological origin. The urine was exposed to cell cultures, and the urine's capacity for inducing apoptosis in the cultures was analysed. A statistical analysis was then conducted to assess whether the apoptotic effect was associated with the symptoms.
Results: After performing an analysis of the association between the degree of apoptotic effect and the symptoms of patients with interstitial cystitis, we observed a significant increase in the mean percentages of apoptosis as the degree of symptom severity increased. After analysing the association between the apoptotic effect and symptoms, we obtained a positive correlation in the patients with interstitial cystitis and a lack of correlation in the patients with chronic pelvic pain of gynaecological origin. The rates of apoptosis increased progressively in the patients with interstitial cystitis as the symptoms increased, white the patients with chronic pelvic pain of gynaecological origin remained stable.
Conclusions: The apoptotic effect of the urine of patients with interstitial cystitis could be a marker of disease, thus differentiating patients with interstitial cystitis from patients with chronic pelvic pain. The effect could also provide an objective measure of symptom severity. (C) 2017 AEU. Published by Elsevier Espana, S.L.U. All rights reserved.Biomarker; Interstitial cystitis; DiagnosisELSEVIER ESPANAspainfo:eu-repo/semantics/restrictedAccess2018-05-01oai:cipf.fundanetsuite.com:p12022026-03-24T12:10:10ZpubrevGRAM-CNN: a deep learning approach with local context for named entity recognition in biomedical textZhu, QLLi, XLConesa, APereira, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1202info:doi:10.1093/bioinformatics/btx815BIOINFORMATICSISSN: 13674803ISSNe: 13674811info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionMotivation: Best performing named entity recognition (NER) methods for biomedical literature are based on hand-crafted features or task-specific rules, which are costly to produce and difficult to generalize to other corpora. End-to-end neural networks achieve state-of-the-art performance without hand-crafted features and task-specific knowledge in non-biomedical NER tasks. However, in the biomedical domain, using the same architecture does not yield competitive performance compared with conventional machine learning models.
Results: We propose a novel end-to-end deep learning approach for biomedical NER tasks that leverages the local contexts based on n-gram character and word embeddings via Convolutional Neural Network (CNN). We call this approach GRAM-CNN. To automatically label a word, this method uses the local information around a word. Therefore, the GRAM-CNN method does not require any specific knowledge or feature engineering and can be theoretically applied to a wide range of existing NER problems. The GRAM-CNN approach was evaluated on three well-known biomedical datasets containing different BioNER entities. It obtained an F1-score of 87.26% on the Biocreative II dataset, 87.26% on the NCBI dataset and 72.57% on the JNLPBA dataset. Those results put GRAM-CNN in the lead of the biological NER methods. To the best of our knowledge, we are the first to apply CNN based structures to BioNER problems.OXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-05-01oai:cipf.fundanetsuite.com:p12032026-03-24T12:10:10ZpubrevRecent Developments and Applications of the Chiral BrOnsted Acid Catalyzed Allylboration of Carbonyl CompoundsSedgwick, DMGrayson, MNFustero, SBarrio, Phttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1203info:doi:10.1055/s-0036-1589532SYNTHESIS-STUTTGARTISSN: 00397881ISSNe: 1437210Xinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe 50-year-old allylboration reaction has seen dramatic developments since the dawn of the new century after the first catalytic asymmetric versions came into play. In the past decade alone, several methodologies capable of achieving the desired homoallylic alcohols in over 90% ee have been developed. This review focuses on the chiral BrOnsted acid catalyzed allylboration reaction, covering everything from the very first examples and precedents to modern day variations and applications.asymmetric synthesis; allylboration; enantioselective catalysis; chiral BrOnsted acids; homoallylic alcohols; DFT calculationsGEORG THIEME VERLAG KGenginfo:eu-repo/semantics/restrictedAccess2018-05-01oai:cipf.fundanetsuite.com:p12042026-04-06T13:29:27ZpubrevMetal-Free and User-Friendly Regioselective Hydroxyfluorination of OlefinsSedgwick, DMLopez, IRoman, RKobayashi, NOkoromoba, OEXu, BHammond, GBBarrio, PFustero, Shttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1204info:doi:10.1021/acs.orglett.8b00681ORGANIC LETTERSISSN: 15237060ISSNe: 15237052info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionA simple, user-friendly, metal-free protocol for the regioselective anti-Markovnikov hydrofluorination of olefins using readily available and inexpensive reagents has been developed. This new approach displays a broader scope than previously reported methodologies and has been applied to the late-stage fluorination of a complex molecule, giving rise to a fluorosteroid derivative. The stereochemistry of the process has also been studied in some detail.AMER CHEMICAL SOCenginfo:eu-repo/semantics/restrictedAccess2018-04-20oai:cipf.fundanetsuite.com:p12052026-03-24T12:10:10ZpubrevBehavioral addictions in early-onset Parkinson disease are associated with DRD3 variantsCastro-Martinez, XHGarcia-Ruiz, PJMartinez-Garcia, CMartinez-Castrillo, JCVela, LMata, MMartinez-Torres, IFeliz-Feliz, CPalau, Fhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1205info:doi:10.1016/j.parkreldis.2018.01.010PARKINSONISM & RELATED DISORDERSISSN: 13538020ISSNe: 18735126info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionBackground: Impulse control disorders (ICDs) comprise abnormal behaviors frequently found in patients with Parkinson's disease (PD) receiving antiparkinsonian medication. ICDs in PD would develop when dopaminergic treatment overstimulates the dopamine receptor D3 (DR3). Here we studied whether DR3 gene (DRD3) is associated to ICD in PD patients with early-onset (EOPD).
Methods: We performed association analysis of the rs6280 DRD3 single nucleotide variation (SNV) (Ser9Gly) in a clinical sample of 126 non early-onset PD (NEOPD) and 73 EOPD (age at onset <45). ICD was evaluated using the Questionnaire for Impulsive-Compulsive Disorders (QUIP) in PD.
Results: In the total sample, we found that a younger onset of PD is linked to ICD traits with a potentially addictive reinforcement (ICDARs, behavioral addictions) (p = .017) and a trend for total ICDs (p = .078) while punding was not associated (p =.75). EOPD sample showed an increase of DRD3 C+ genotype for ICD (p = .022) and ICDARs (p = .043) but not for punding (p = .170). The post-hoc analyses including the time of evolution and Pramipexol or Ropinirole treatments, confirmed the independent effect of the DRD3 upon ICDs (p = .028) and ICDARs (p = .041) as well as the interaction between DRD3 and Pramipexol treatment upon ICDARs (OR = 4.60, 95% CI 1.20-17.632, p = .026). The NEOPD group showed no association between DRD3 and ICDs.
Conclusions: We found that behavioral addictions in PD are associated with an early onset of the disease, the rs6280 DRD3 SNV and the type of dopamine agonist Further investigation in independent samples is warranted. (C) 2018 Elsevier Ltd. All rights reserved.DRD3; Parkinson; Impulse control disordersELSEVIER SCI LTDenginfo:eu-repo/semantics/restrictedAccess2018-04-01oai:cipf.fundanetsuite.com:p12062026-04-06T13:29:27ZpubrevRapid two-dimensional ALSOFAST-HSQC experiment for metabolomics and fluxomics studies: application to a C-13-enriched cancer cell model treated with gold nanoparticlesSchatzlein, MPBecker, JSchulze-Sunninghausen, DPineda-Lucena, AHerance, JRLuy, Bhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1206info:doi:10.1007/s00216-018-0961-6ANALYTICAL AND BIOANALYTICAL CHEMISTRYISSN: 16182642ISSNe: 16182650info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionIsotope labeling enables the use of C-13-based metabolomics techniques with strongly improved resolution for a better identification of relevant metabolites and tracing of metabolic fluxes in cell and animal models, as required in fluxomics studies. However, even at high NMR-active isotope abundance, the acquisition of one-dimensional C-13 and classical two-dimensional H-1,C-13-HSQC experiments remains time consuming. With the aim to provide a shorter, more efficient alternative, herein we explored the ALSOFAST-HSQC experiment with its rapid acquisition scheme for the analysis of C-13-labeled metabolites in complex biological mixtures. As an initial step, the parameters of the pulse sequence were optimized to take into account the specific characteristics of the complex samples. We then applied the fast two-dimensional experiment to study the effect of different kinds of antioxidant gold nanoparticles on a HeLa cancer cell model grown on C-13 glucose-enriched medium. As a result, H-1,C-13-2D correlations could be obtained in a couple of seconds to few minutes, allowing a simple and reliable identification of various C-13-enriched metabolites and the determination of specific variations between the different sample groups. Thus, it was possible to monitor glucose metabolism in the cell model and study the antioxidant effect of the coated gold nanoparticles in detail. Finally, with an experiment time of only half an hour, highly resolved H-1,C-13-HSQC spectra using the ALSOFAST-HSQC pulse sequence were acquired, revealing the isotope-position-patterns of the corresponding C-13-nuclei from carbon multiplets.Fast NMR; HSQC; Metabolomics; Fluxomics; Gold nanoparticlesSPRINGER HEIDELBERGenginfo:eu-repo/semantics/restrictedAccess2018-04-01oai:cipf.fundanetsuite.com:p12072026-04-06T13:29:27ZpubrevA Preview of Selected Articles - April 2018Atkinson, SPhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1207info:doi:10.1002/stem.2807STEM CELLSISSN: 10665099ISSNe: 15494918info:eu-repo/semantics/lectureEditorial Materialinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-04-01oai:cipf.fundanetsuite.com:p12082026-04-06T13:29:27ZpubrevMetabolomics facilitates the discrimination of the specific and-cancer effects of free and polymer conjugated doxorubicin in breast cancer modelsArminan, APalomino-Schatzlein, MArroyo-Crespo, JJVicente-Ruiz, SVicent, MJPineda-Lucena, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1208info:doi:10.1016/j.biomaterials.2018.02.015BIOMATERIALSISSN: 01429612ISSNe: 18785905info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionMetabolomics is becoming a relevant tool for understanding the molecular mechanisms involved in the response to new drug delivery systems. The applicability of this experimental approach to cell cultures and animal models makes metabolomics a useful tool for establishing direct connections between in vitro and in vivo data, thus providing a reliable platform for the characterization of chemotherapeutic agents. Herein, we used metabolomic profiles based on nuclear magnetic resonance (NMR) spectroscopy to evaluate the biochemical pathways involved in the response to a chemotherapeutic anthracycline drug (Doxorubicin, Dox) and an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-conjugated form (HPMA-Dox) in an in vitro cell culture model and an in vivo orthotopic breast cancer model. We also used protein expression and flow cytometry studies to obtain a better coverage of the biochemical alterations associated with the administration of these compounds. The overall analysis revealed that polymer conjugation leads to increased apoptosis, reduced glycolysis, and reduced levels of phospholipids when compared to the free chemotherapeutic drug. Our results represent a first step in the application of integrated in vitro and in vivo metabolomic studies to the evaluation of drug delivery systems. (C) 2018 The Authors. Published by Elsevier Ltd.Metabolomics; NMR; Nanomedicine; Polymer therapeutics; Breast cancerELSEVIER SCI LTDenginfo:eu-repo/semantics/openAccess2018-04-01oai:cipf.fundanetsuite.com:p12092026-04-06T13:29:27ZpubrevCytochrome c speeds up caspase cascade activation by blocking 14-3-3 epsilon-dependent Apaf-1 inhibitionElena-Real, CADiaz-Quintana, AGonzalez-Arzola, KVelazquez-Campoy, AOrzaez, MLopez-Rivas, AGil-Caballero, SDe la Rosa, MADiaz-Moreno, Ihttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1209info:doi:10.1038/s41419-018-0408-1Cell Death & DiseaseISSN: 20414889info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionApoptosis is a highly regulated form of programmed cell death, essential to the development and homeostasis of multicellular organisms. Cytochrome c is a central figure in the activation of the apoptotic intrinsic pathway, thereby activating the caspase cascade through its interaction with Apaf-1. Our recent studies have revealed 14-3-3 epsilon (a direct inhibitor of Apaf-1) as a cytosolic cytochrome c target. Here we explore the cytochrome c / 14-3-3 epsilon interaction and show the ability of cytochrome c to block 14-3-3 epsilon-mediated Apaf-1 inhibition, thereby unveiling a novel function for cytochrome c as an indirect activator of caspase-9/3. We have used calorimetry, NMR spectroscopy, site mutagenesis and computational calculations to provide an insight into the structural features of the cytochrome c / 14-3-3 epsilon complex. Overall, these findings suggest an additional cytochrome c-mediated mechanism to modulate apoptosome formation, shedding light onto the rigorous apoptotic regulation network.SPRINGERNATUREenginfo:eu-repo/semantics/restrictedAccess2018-03-06oai:cipf.fundanetsuite.com:p12102026-03-24T12:10:10ZpubrevIncreasing extracellular cGMP in cerebellum in vivo reduces neuroinflammation, GABAergic tone and motor in-coordination in hyperammonemic ratsCabrera-Pastor, ABalzano, THernandez-Rabaza, VMalaguarnera, MLlansola, MFelipo, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1210info:doi:10.1016/j.bbi.2017.12.013BRAIN BEHAVIOR AND IMMUNITYISSN: 08891591ISSNe: 10902139info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionHyperammonemia is a main contributor to cognitive impairment and motor in-coordination in patients with hepatic encephalopathy. Hyperammonemia-induced neuroinflammation mediates the neurological alterations in hepatic encephalopathy. Intracerebral administration of extracellular cGMP restores some but not all types of cognitive impairment. Motor in-coordination, is mainly due to increased GABAergic tone in cerebellum. We hypothesized that extracellular cGMP would restore motor coordination in hyperammonemic rats by normalizing GABAergic tone in cerebellum and that this would be mediated by reduction of neuroinflammation.
The aims of this work were to assess whether chronic intracerebral administration of cGMP to hyperammonemic rats: 1) restores motor coordination: 2) reduces neuroinflammation in cerebellum: 3) reduces extracellular GABA levels and GABAergic tone in cerebellum: and also 4) to provide some advance in the understanding on the molecular mechanisms involved.
The results reported show that rats with chronic hyperammonemia show neuroinflammation in cerebellum, including microglia and astrocytes activation and increased levels of IL-1b and TNFa and increased membrane expression of the TNFa receptor. This is associated with increased glutaminase expression and extracellular glutamate, increased amount of the GABA transporter GAT-3 in activated astrocytes, increased extracellular GABA in cerebellum and motor in-coordination. Chronic intracerebral administration of extracellular cGMP to rats with chronic hyperammonemia reduces neuroinflammation, including microglia and astrocytes activation and membrane expression of the TNFa receptor. This is associated with reduced nuclear NF-kappa B, glutaminase expression and extracellular glutamate, reduced amount of the GABA transporter GAT-3 in activated astrocytes and reduced extracellular GABA in cerebellum and restoration of motor coordination.
The data support that extracellular cGMP restores motor coordination in hyperammdnemic rats by reducing microglia activation and neuroinflammation, leading to normalization of extracellular glutamate and GABA levels in cerebellum and of motor coordination. (C) 2018 Elsevier Inc. All rights reserved.Extracellular cGMP; Hyperammonemia; Motor in-coordination; Neuroinflammation; Microglia activation; TNFa receptor; Glutaminase; Extracellular glutamate; Extracellular GABA; CerebellumACADEMIC PRESS INC ELSEVIER SCIENCEenginfo:eu-repo/semantics/restrictedAccess2018-03-01oai:cipf.fundanetsuite.com:p12112026-03-24T12:10:10ZpubrevSQANTI: extensive characterization of long-read transcript sequences for quality control in full-length transcriptome identification and quantificationTardaguila, Mde la Fuente, LMarti, CPereira, CPardo-Palacios, FJdel Risco, HFerrell, MMellado, MMacchietto, MVerheggen, KEdelmann, MEzkurdia, IVazquez, JTress, MMortazavi, AMartens, LRodriguez-Navarro, SMoreno-Manzano, VConesa, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1211info:doi:10.1101/gr.222976.117GENOME RESEARCHISSN: 10889051ISSNe: 15495469info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionHigh-throughput sequencing of full-length transcripts using long reads has paved the way for the discovery of thousands of novel transcripts, even in well-annotated mammalian species. The advances in sequencing technology have created a need for studies and tools that can characterize these novel variants. Here, we present SQANTI, an automated pipeline for the classification of long-read transcripts that can assess the quality of data and the preprocessing pipeline using 47 unique descriptors. We apply SQANTI to a neuronal mouse transcriptome using Pacific Biosciences (PacBio) long reads and illustrate how the tool is effective in characterizing and describing the composition of the full-length transcriptome. We perform extensive evaluation of ToFU PacBio transcripts by PCR to reveal that an important number of the novel transcripts are technical artifacts of the sequencing approach and that SQANTI quality descriptors can be used to engineer a filtering strategy to remove them. Most novel transcripts in this curated transcriptome are novel combinations of existing splice sites, resulting more frequently in novel ORFs than novel UTRs, and are enriched in both general metabolic and neural-specific functions. We show that these new transcripts have a major impact in the correct quantification of transcript levels by state-of-the-art short-read-based quantification algorithms. By comparing our iso-transcriptome with public proteomics databases, we find that alternative isoforms are elusive to proteogenomics detection. SQANTI allows the user to maximize the analytical outcome of long-read technologies by providing the tools to deliver quality-evaluated and curated full-length transcriptomes.COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPTenginfo:eu-repo/semantics/restrictedAccess2018-03-01oai:cipf.fundanetsuite.com:p12122026-04-06T13:29:27ZpubrevThe Cerebellum of Patients with Steatohepatitis Shows Lymphocyte Infiltration, Microglial Activation and Loss of Purkinje and Granular NeuronsBalzano, TForteza, JMolina, PGiner, JMonzo, ASancho-Jimenez, JUrios, AMontoliu, CFelipo, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1212info:doi:10.1038/s41598-018-21399-6Scientific ReportsISSN: 20452322info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPeripheral inflammation contributes to minimal hepatic encephalopathy in chronic liver diseases, which could be mediated by neuroinflammation. Neuroinflammation in cerebellum of patients with chronic liver diseases has not been studied in detail. Our aim was to analyze in cerebellum of patients with different grades of liver disease, from mild steatohepatitis to cirrhosis and hepatic encephalopathy: (a) neuronal density in Purkinje and granular layers; (b) microglial activation; (c) astrocyte activation; (d) peripheral lymphocytes infiltration; (e) subtypes of lymphocytes infiltrated. Steatohepatitis was classified as SH1, SH2 and SH3. Patients with SH1 show Th17 and Tfh lymphocytes infiltration in the meninges, microglia activation in the molecular layer and loss of 16 +/- 4% of Purkinje and 19 +/- 2% of granular neurons. White matter remains unaffected. With the progression of liver disease to worse stages (SH2, SH3, cirrhosis) activation of microglia and astrocytes extends to white matter, Bergman glia is damaged in the molecular layer and there is a further loss of Purkinje neurons. The results reported show that neuroinflammation in cerebellum occurs at early stages of liver disease, even before reaching cirrhosis. Neuroinflammation occurs earlier in the molecular layer than in white matter, and is associated with infiltration of peripheral Th17 and Tfh lymphocytes.NATURE PORTFOLIOenginfo:eu-repo/semantics/restrictedAccess2018-02-14oai:cipf.fundanetsuite.com:p12132026-04-06T13:29:27ZpubrevHyperammonemia alters membrane expression of GluA1 and GluA2 subunits of AMPA receptors in hippocampus by enhancing activation of the IL-1 receptor: underlying mechanismsTaoro-Gonzalez, LArenas, YMCabrera-Pastor, AFelipo, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1213info:doi:10.1186/s12974-018-1082-zJournal of NeuroinflammationISSN: 17422094info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionBackground: Hyperammonemic rats reproduce the cognitive alterations of patients with hepatic encephalopathy, including altered spatial memory, attributed to altered membrane expression of AMPA receptor subunits in hippocampus. Neuroinflammation mediates these cognitive alterations. We hypothesized that hyperammonemia-induced increase in IL-1 beta in hippocampus would be responsible for the altered GluA1 and GluA2 membrane expression. The aims of this work were to (1) assess if increased IL-1 beta levels and activation of its receptor are responsible for the changes in GluA1 and/or GluA2 membrane expression in hyperammonemia and (2) identify the mechanisms by which activation of IL-1 receptor leads to altered membrane expression of GluA1 and GluA2.
Methods: We analyzed in hippocampal slices from control and hyperammonemic rat membrane expression of AMPA receptors using the BS3 cross-linker and phosphorylation of the GluA1 and GluA2 subunits using phosphor-specific antibodies. The IL-1 receptor was blocked with IL-Ra, and the signal transduction pathways involved in modulation of membrane expression of GluA1 and GluA2 were analyzed using inhibitors of key steps.
Results: Hyperammonemia reduces GluA1 and increases GluA2 membrane expression and reduces phosphorylation of GluA1 at Ser831 and of GluA2 at Ser880. Hyperammonemia increases IL-1 beta, enhancing activation of IL-1 receptor. This leads to activation of Src. The changes in membrane expression of GluA1 and GluA2 are reversed by blocking the IL-1 receptor with IL-1Ra or by inhibiting Src with PP2. After Src activation, the pathways for GluA2 and GluA1 diverge. Src increases phosphorylation of GluN2B at Tyr14721 and membrane expression of GluN2B in hyperammonemic rats, leading to activation of MAP kinase p38, which binds to and reduces phosphorylation at Thr560 and activity of PKC zeta, resulting in reduced phosphorylation at Ser880 and enhanced membrane expression of GluA2. Increased Src activity in hyperammonemic rats also activates PKC delta which enhances phosphorylation of GluN2B at Ser1303, reducing membrane expression of CaMKII and phosphorylation at Ser831 and membrane expression of GluA1.
Conclusions: This work identifies two pathways by which neuroinflammation alters glutamatergic neurotransmission in hippocampus. The steps of the pathways identified could be targets to normalize neurotransmission in hyperammonemia and other pathologies associated with increased IL-1 beta by acting, for example, on p38 or PKC delta.Neuroinflammation; IL-1 beta; IL-1 receptor; Hyperammonemia; Hepatic encephalopathy; AMPA receptors; GluA1; GluA2; Membrane expression; NeurotransmissionBMCenginfo:eu-repo/semantics/restrictedAccess2018-02-08oai:cipf.fundanetsuite.com:p12142026-03-24T12:10:10ZpubrevEndosulfan and Cypermethrin Pesticide Mixture Induces Synergistic or Antagonistic Effects on Developmental Exposed Rats Depending on the Analyzed Behavioral or Neurochemical End PointsLlansola, MCabrera-Pastor, AHernandez-Rabaza, VAgusti, AFelipo, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1214info:doi:10.1021/acschemneuro.7b00364ACS Chemical NeuroscienceISSN: 19487193info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionExposure to pesticides has been associated with neurodevelopmental toxicity. Usually people are exposed to mixtures of pesticides. However, most studies analyze the effects of individual pesticides. Developmental exposure to mixtures of pesticides may result in additive effects or in antagonistic or synergistic effects. The aim of this work was to compare the effects of developmental exposure of rats to cypermethrin or endosulfan with the effects of its mixture on cognitive and motor function and on some underlying mechanisms. Exposure to individual pesticides or the mixture was from gestational day 7 to postnatal day 21. We analyzed the effects, in males and females, on spatial learning and memory, associative learning, anxiety, motor coordination, and spontaneous motor activity. We also analyzed neuroinflammation and NMDA receptor subunits in hippocampus and extracellular GABA in cerebellum. Exposure to the mixture, but not to individual pesticides, impaired spatial memory in males, associative learning in females, and increased motor activity in males and females. This indicates a synergistic effect of cypermethrin and endolsufan exposure on these end points. In contrast, motor coordination was impaired by individual exposure to endosulfan or cypermethrin, associated with increased extracellular GABA in cerebellum, but these effects were prevented in rats exposed to the mixture, indicating an antagonistic effect of cypermethrin and endolsufan exposure on these end points. The results show different interaction modes (synergism or antagonism) of the pesticides, depending on the end point analyzed and the sex of the rats.Pesticide mixture; learning; memory; motor function; cytokines; neurotransmissionAMER CHEMICAL SOCenginfo:eu-repo/semantics/restrictedAccess2018-02-01oai:cipf.fundanetsuite.com:p12152026-03-24T12:10:10ZpubrevElectrospun poly(hydroxybutyrate) scaffolds promote engraftment of human skin equivalents via macrophage M2 polarization and angiogenesisCastellano, DSanchis, ABlanes, Mdel Caz, MDPRuiz-Sauri, APiquer-Gil, MPelacho, BMarco, BGarcia, NOntoria-Oviedo, ICambra, VProsper, FSepulveda, Phttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1215info:doi:10.1002/term.2420Journal of Tissue Engineering and Regenerative MedicineISSN: 19326254ISSNe: 19327005info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionHuman dermo-epidermal skin equivalents (DE) comprising in vitro expanded autologous keratinocytes and fibroblasts are a good option for massive burn treatment. However, the lengthy expansion time required to obtain sufficient surface to cover an extensive burn together with the challenging surgical procedure limits their clinical use. The integration of DE and biodegradable scaffolds has been proposed in an effort to enhance their mechanical properties. Here, it is shown that poly(hydroxybutyrate) electrospun scaffolds (PHB) present good biocompatibility both in vitro and in vivo and are superior to poly-epsilon-caprolactone electrospun scaffolds as a substrate for skin reconstruction. Implantation of PHB scaffolds in healthy rats polarized macrophages to an M2-type that promoted constructive in vivo remodelling. Moreover, implantation of DE-PHB composites in a NOD/SCID mouse xenograft model resulted in engraftment accompanied by an increase in angiogenesis that favoured the survival of the human graft. Thus, PHB scaffolds are an attractive substrate for further exploration in skin reconstruction procedures, probably due in part to their greater angiogenic and M2 macrophage polarization properties. Copyright (c) 2017 John Wiley & Sons, Ltd.poly(hydroxybutyrate); electrospinning; skin equivalents; human skin xenograftWILEYenginfo:eu-repo/semantics/restrictedAccess2018-02-01oai:cipf.fundanetsuite.com:p12162026-03-24T12:10:10ZpubrevA metal-free and regioselective approach to (Z)-beta-fluorovinyl sulfones and their chemoselective hydrogenation to beta-fluoroalkyl sulfonesSedgwick, DMRoman, RBarrio, PMorales, CFustero, Shttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1216info:doi:10.1016/j.jfluchem.2017.12.016JOURNAL OF FLUORINE CHEMISTRYISSN: 00221139ISSNe: 18733328info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionA highly regioselective, metal-free hydrofluorination reaction of alkynyl sulfones was developed using TBAF-one of the cheapest and most commonly available fluoride sources. In addition, the reactivity of the resulting beta-fluorovinyl sulfones was studied, focusing on their selective hydrogenation reaction. Both beta-fluor vinyl sulfones and their hydrogenation products beta-fluoroalkyl sulfones may find applications in medicinal and agrochemical sciences.Regioselectivity; Alkynyl sulfones; beta-Fluorovinyl sulfones; Hydrogenation; Chemoselectivity; beta-Fluoroalkyl sulfonesELSEVIER SCIENCE SAenginfo:eu-repo/semantics/restrictedAccess2018-02-01oai:cipf.fundanetsuite.com:p12172026-03-24T12:10:10ZpubrevIdentification and visualization of differential isoform expression in RNA-seq time seriesNueda, MJMarti, CTarazona, SConesa, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1217info:doi:10.1093/bioinformatics/btx578BIOINFORMATICSISSN: 13674803ISSNe: 13674811info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionMotivation: As sequencing technologies improve their capacity to detect distinct transcripts of the same gene and to address complex experimental designs such as longitudinal studies, there is a need to develop statistical methods for the analysis of isoform expression changes in time series data.
Results: Iso-maSigPro is a new functionality of the R package maSigPro for transcriptomics time series data analysis. Iso-maSigPro identifies genes with a differential isoform usage across time. The package also includes new clustering and visualization functions that allow grouping of genes with similar expression patterns at the isoform level, as well as those genes with a shift in major expressed isoform.
Availability and implementation: The package is freely available under the LGPL license from the Bioconductor web site.
Contact: mj.nueda@ua.es or aconesa@ufl.edu
Supplementary information: Supplementary data are available at Bioinformatics online.OXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-02-01oai:cipf.fundanetsuite.com:p12182026-04-06T13:29:27ZpubrevA Preview of Selected ArticlesAtkinson, SPhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1218info:doi:10.1002/stem.2770STEM CELLSISSN: 10665099ISSNe: 15494918info:eu-repo/semantics/lectureEditorial Materialinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2018-02-01oai:cipf.fundanetsuite.com:p12192026-03-24T12:10:10ZpubrevDevelopmental Exposure to Pesticides Alters Motor Activity and Coordination in Rats: Sex Differences and Underlying MechanismsFelipo, VCabrera-Pastor, AAgusti, AHernandez-Rabaza, VLlansola, Mhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1219info:doi:10.1007/s12640-017-9823-9NEUROTOXICITY RESEARCHISSN: 10298428ISSNe: 14763524info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionIt has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous motor activity and motor coordination of developmental exposure to a representative pesticide of each one of the four main chemical families: organophosphates (chlorpyrifos), carbamates (carbaryl), organochlorines (endosulfan), and pyrethroids (cypermethrin). Pesticides were administered once a day orally, in a sweet jelly, from gestational day 7 to post natal day 21. Spontaneous motor activity was assessed by an actimeter and motor coordination using the rotarod, when rats were adults. The effects were analyzed separately in males and females. Extracellular GABA in cerebellum and NMDA receptor subunits in hippocampus were assessed as possible underlying mechanisms of motor alterations. Motor coordination was impaired by developmental exposure to endosulfan, cypermethrin, and chlorpyrifos in females but not in males. The effect of endosulfan and cypermethrin would be due to increased extracellular GABA in cerebellum, which remains unaltered in male rats. Chlorpyrifos increased motor activity in males and females. Cypermethrin decreased motor activity mainly in males. In male rats, but not in females, expression of the NR2B subunit of NMDA receptor in hippocampus correlated with motor activity. These results show sex-specific effects of different pesticides on motor activity and coordination, associated with neurotransmission alterations. These data contribute to better understand the relationship between developmental exposure to the main pesticide families and motor disorders in children.Pesticides; Sex; Neurotransmission; Motor function; DevelopmentSPRINGERenginfo:eu-repo/semantics/restrictedAccess2018-02-01oai:cipf.fundanetsuite.com:p12202026-04-06T13:29:27ZpubrevDevelopment of inhibitors of receptor protein tyrosine phosphatase beta/zeta (PTPRZ1) as candidates for CNS disordersPastor, MFernandez-Calle, RDi Geronimo, BVicente-Rodriguez, MZapico, JMGramage, ECoderch, CPerez-Garcia, CLasek, AWPuchades-Carrasco, LPineda-Lucena, Ade Pascual-Teresa, BHerradon, GRamos, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1220info:doi:10.1016/j.ejmech.2017.11.080EUROPEAN JOURNAL OF MEDICINAL CHEMISTRYISSN: 02235234ISSNe: 17683254info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionA new series of blood-brain barrier permeable molecules designed to mimic the activity of Pleiotrophin in the CNS has been designed and synthesized. These compounds exert their action by interacting with the intracellular domain PD1 of the Protein Tyrosine-Phosphatase Receptor Z1 (PTPRZ1), and inhibiting its tyrosine phosphatase activity. The most potent compounds 10a and 12b (IC50 = 0,1 mu M) significantly increase the phosphorylation of key tyrosine residues of PTPRZ1 substrates involved in neuronal survival and differentiation, and display protective effects against amphetamine-induced toxicity. Docking and molecular dynamics experiments have been used to analyze the binding mode and to explain the observed selectivity against PTP1B. An In vivo experiment has demonstrated that 10a can cross the BBB, thus promoting the possibility of moving forward these candidates for the development of drugs for the treatment of CNS disorders, such as drug addiction and neurodegenerative diseases. (C) 2017 Elsevier Masson SAS. All rights reserved.PTPRZ1; CNS disorders; Drug addiction; Molecular dynamics; SynthesisELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIERenginfo:eu-repo/semantics/restrictedAccess2018-01-20oai:cipf.fundanetsuite.com:p12212026-03-24T12:10:10ZpubrevAsymmetric Vinylogous Mannich-Type Addition of ,-Dicyanoalkenes to -Fluoroalkyl Sulfinyl IminesSanz-Vidal, ATorres, JSoloshonok, VAZhu, YHan, JLFustero, Sdel Pozo, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1221info:doi:10.1002/adsc.201701284ADVANCED SYNTHESIS & CATALYSISISSN: 16154150ISSNe: 16154169info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe asymmetric vinylogous Mannich reaction (AVMR) of ,-dicyanoalkenes with -fluoroalkyl sulfinyl imines has been successfully accomplished. This transformation is unprecedented with fluorinated imines and, at the same time, the use of dicyanoalkenes in AVMR has been scarcely reported. Several fluorinated sulfinyl imines are compatible with the process, which gives access to a family of chiral fluorinated amines with an excellent level of stereocontrol. Interestingly, the selectivity found in our protocol is the opposite of that encountered in analogous, previously reported AVMRs. Additionally, the synthetic applicability of the addition products has been exemplified with several transformations showing the particular reactivity of the dicyanoalkene moiety of these -fluorinated amines.asymmetric vinylogous mannich addition; chiral -fluorinated amines; dicyanoalkenes; fluorinated sulfinyl iminesWILEY-V C H VERLAG GMBHenginfo:eu-repo/semantics/restrictedAccess2018-01-17oai:cipf.fundanetsuite.com:p12222026-04-06T13:29:27ZpubrevPrognostic value of quantitative ctDNA levels in non small cell lung cancer patientsProvencio, MTorrente, MCalvo, VPerez-Callejo, DGutierrez, LFranco, FPerez-Barrios, CBarquin, MRoyuela, AGarcia-Garcia, FBueno, CGarcia-Grande, ACamps, CMassuti, BSotomayor, ERomero, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1222info:doi:10.18632/oncotarget.22470OncotargetISSN: 19492553info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionBackground: Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels.
Materials and Methods: A total of 251 serial plasma samples from 41 non-small-cell lung cancer patients who carried an activating EGFR mutation were analysed by digital PCR. For survival analysis, ctDNA levels were computed as a time-dependent covariate.
Results: Dynamic ctDNA measurements had prognostic significance (hazard ratio for overall survival and progression free survival according to p.T790M mutant allele frequency; 2.676 and 2.71 respectively; P < 0.05). In the same way, patients with p.T790M-negative or unchanging or decreasing plasma levels of sensitizing EGFR mutation were 12 and 4.8 times more likely to maintain response or stable disease, respectively, than patients in which the opposite occurred (P < 0.05). On average, the p.T790M mutation was detected in plasma 51 days before the assessment of progression disease by CT-scan. Finally, ctDNA outperformed CTCs for assessing tumor progression (P = 0.021).
Conclusions: The appearance or increase in a unit of the p.T790M allele frequency almost triples the risk of death and progression. This information can be used to design clinical trials aiming to estimate whether T790M positive patients should start second line treatment based on molecular data rather than imaging data.ctDNA; non-small cell lung cancer; tyrosine kinase inhibitor; EGFRIMPACT JOURNALS LLCenginfo:eu-repo/semantics/restrictedAccess2018-01-02oai:cipf.fundanetsuite.com:p12242026-03-24T12:10:10ZpubrevAnilinopyridine-metal complexes for the selective chromogenic sensing of cyanide anionLozano-Torres, BMarcos, MDPardo, TSancenon, FMartinez-Manez, RRurack, Khttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1224info:doi:10.1080/00958972.2018.1434719JOURNAL OF COORDINATION CHEMISTRYISSN: 00958972ISSNe: 10290389info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionProbe 1, which contains an anilinopyridine chromophore and an aza-oxa macrocyclic subunit, presented an absorption band centered at 340 nm in acetonitrile. Addition of Fe(III), Cr(III) and Hg(II) induced the growth of a new absorption band at 430 nm (with color change from colorless to yellow), whereas in the presence of Cu(II), Zn(II) and Pb(II), less marked changes were observed. The color changes observed upon addition of Fe(III), Cr(III) and Hg(II) were ascribed to the formation of 1:1 stoichiometry complexes with probe 1. Coordination of Fe(III), Cr(III) and Hg(II) with the pyridine fragment of 1 induced an enhancement of the charge transfer character accompanied with a marked bathochromic shift that was reflected in a color change from colorless to yellow. The strength of the interaction between probe 1 and Fe(III) cation was modulated upon interaction with anions. Of all the anions tested, only cyanide was able to induce the bleaching of the yellow 1<bold>Fe</bold>(III) complex solution. This bleaching was ascribed to the formation of 1<bold>Fe</bold>(III)-CN complex that restored, to some extent, the optical features of the free probe allowing the chromogenic sensing of cyanide. Besides, 1<bold>Fe</bold>(III) complex was used to detect cyanide in acetonitrile-water 90:10 v/v mixtures with good recoveries.
[GRAPHICS]
.Anilinopyridine; charge-transfer; Fe(III) complex; chromogenic; cyanideTAYLOR & FRANCIS LTDenginfo:eu-repo/semantics/restrictedAccess2018-01-01oai:cipf.fundanetsuite.com:p12252026-03-24T12:10:10ZpubrevCirrhotic patients with minimal hepatic encephalopathy have increased capacity to eliminate superoxide and peroxynitrite in lymphocytes, associated with cognitive impairmentGimenez-Garzo, CUrios, AAgusti, AMangas-Losada, AGarcia-Garcia, REscudero-Garcia, DKosenko, EOrdono, JFTosca, JGiner-Duran, RSerra, MAFelipo, VMontoliu, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1225info:doi:10.1080/10715762.2017.1420183FREE RADICAL RESEARCHISSN: 10715762ISSNe: 10292470info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPatients with minimal hepatic encephalopathy (MHE) show increased oxidative stress in blood. We aimed to assess whether MHE patients show alterations in different types of blood cells in (a) basal reactive oxygen and nitrogen species levels; (b) capacity to metabolise these species. To assess the mechanisms involved in the altered capacity to metabolise these species we also analysed: (c) peroxynitrite formation and d) peroxynitrite reaction with biological molecules. Levels of reactive oxygen and nitrogen species were measured by flow cytometry in blood cell populations from cirrhotic patients with and without MHE and controls, under basal conditions and after adding generators of superoxide (plumbagin) or nitric oxide (NOR-1) to assess the capacity to eliminate them. Under basal conditions, MHE patients show reduced superoxide and peroxynitrite levels and increased nitric oxide (NO) and nitrotyrosine levels. In patients without MHE plumbagin strongly increases cellular superoxide, moderately peroxynitrite and reduces NO levels. In MHE patients, plumbagin increases slightly superoxide and strongly peroxynitrite levels and affects slightly NO levels. NOR-1 increases NO levels much less in patients with than without MHE. These data show that the mechanisms and the capacity to eliminate cellular superoxide, NO and peroxynitrite are enhanced in MHE patients. Superoxide elimination is enhanced through reaction with NO to form peroxynitrite which, in turn, is eliminated by enhanced reaction with biological molecules, which could contribute to cognitive impairment in MHE. The data show that basal free radical levels do not reflect the oxidative stress status in MHE.Free radicals; nitric oxide; Psychometric Hepatic Encephalopathy Score; cognitive impairment; nitrotyrosineTAYLOR & FRANCIS LTDenginfo:eu-repo/semantics/restrictedAccess2018-01-01oai:cipf.fundanetsuite.com:p12262026-04-06T13:29:27ZpubrevFM19G11 and Ependymal Progenitor/Stem Cell Combinatory Treatment Enhances Neuronal Preservation and Oligodendrogenesis after Severe Spinal Cord InjuryAlastrue-Agudo, ARodriguez-Jimenez, FJDe Giorgio, FErceg, SMoreno-Manzano, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1226info:doi:10.3390/ijms19010200INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 14220067info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionSpinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. We have previously shown that individual therapeutic strategies, transplantation of ependymal stem/progenitor cells of the spinal cord after injury (epSPCi) or FM19G11 pharmacological treatment, induce moderate functional recovery after SCI. Here, the combination of treatments has been assayed for functional and histological analysis. Immediately after severe SCI, one million epSPCi were intramedullary injected, and the FM19G11 compound or dimethyl sulfoxide (DMSO) (as the vehicle control) was administrated via intrathecal catheterization. The combination of treatments, epSPCi and FM19G11, improves locomotor tasks compared to the control group, but did not significantly improve the Basso, Beattie, Bresnahan (BBB) scores for locomotor analysis in comparison with the individual treatments. However, the histological analysis of the spinal cord tissues, two months after SCI and treatments, demonstrated that when we treat the animals with both epSPCi and FM19G11, an improved environment for neuronal preservation was generated by reduction of the glial scar extension. The combinatorial treatment also contributes to enhancing the oligodendrocyte precursor cells by inducing the expression of Olig1 in vivo. These results suggest that a combination of therapies may be an exciting new therapeutic treatment for more efficient neuronal activity recovery after severe SCI.FM19G11; spinal cord injury; ependymal progenitor stem cells; oligodendrogenesis; locomotion; neuronal regeneration; axon growthMDPIenginfo:eu-repo/semantics/restrictedAccess2018-01-01oai:cipf.fundanetsuite.com:p12272026-04-06T13:29:27ZpubrevQuantitative Determination of Spring Water Quality Parameters via Electronic TongueCarbo, NCarrero, JLGarcia-Castillo, FJTormos, IOlivas, EFolch, EFillol, MASoto, JMartinez-Manez, RMartinez-Bisbal, MChttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1227info:doi:10.3390/s18010040SENSORSISSN: 14248220info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe use of a voltammetric electronic tongue for the quantitative analysis of quality parameters in spring water is proposed here. The electronic voltammetric tongue consisted of a set of four noble electrodes (iridium, rhodium, platinum, and gold) housed inside a stainless steel cylinder. These noble metals have a high durability and are not demanding for maintenance, features required for the development of future automated equipment. A pulse voltammetry study was conducted in 83 spring water samples to determine concentrations of nitrate (range: 6.9-115 mg/L), sulfate (32-472 mg/L), fluoride (0.08-0.26 mg/L), chloride (17-190 mg/L), and sodium (11-94 mg/L) as well as pH (7.3-7.8). These parameters were also determined by routine analytical methods in spring water samples. A partial least squares (PLS) analysis was run to obtain a model to predict these parameter. Orthogonal signal correction (OSC) was applied in the preprocessing step. Calibration (67%) and validation (33%) sets were selected randomly. The electronic tongue showed good predictive power to determine the concentrations of nitrate, sulfate, chloride, and sodium as well as pH and displayed a lower R-2 and slope in the validation set for fluoride. Nitrate and fluoride concentrations were estimated with errors lower than 15%, whereas chloride, sulfate, and sodium concentrations as well as pH were estimated with errors below 10%.spring water; electronic voltammetric tongue; water quality control; partial least squaresMDPIenginfo:eu-repo/semantics/restrictedAccess2018-01-01oai:cipf.fundanetsuite.com:p12282026-03-24T12:10:10Zpubrevoai:cipf.fundanetsuite.com:p12292026-03-24T12:10:10ZpubrevPolymer therapeutics and stem cell therapies as a combinatorial approach for the treatment of chronic spinal cord injuriesNebot, VRequejo-Aguilar, RArminan, AZagorodko, OAlastrue-Agudo, AMoreno-Manzano, VVicent, Mhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1229Abstracts Of Papers Of The American Chemical SocietyISSN: 00657727info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionAMER CHEMICAL SOCenginfo:eu-repo/semantics/restrictedAccess2017-08-20oai:cipf.fundanetsuite.com:p12302026-03-24T12:10:10ZpubrevOrganocatalytic anti-Selective Mannich Reactions with Fluorinated Aldimines: Synthesis of anti-gamma-Fluoroalkyl-gamma-amino AlcoholsFustero, SMojarrad, FCarrion, MDPSanz-Cervera, JFAcena, JLhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1230info:doi:10.1002/ejoc.200900509EUROPEAN JOURNAL OF ORGANIC CHEMISTRYISSN: 1434193XISSNe: 10990690info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe asymmetric Mannich reaction between fluoroalkyl aldimines and aldehydes catalyzed by alpha,alpha-diphenylprolinol trimethylsilyl ether is reported. The corresponding Mannich adducts were reduced in situ to afford anti-beta-alkyl-gamma-fluoroalkyl-gamma-amino alcohols in moderate yields and with very high diastereo- and enantioselectivities. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)Organocatalysis; Enantioselectivity; Mannich reaction; Fluorinated imines; Amino alcoholsWILEY-V C H VERLAG GMBHenginfo:eu-repo/semantics/restrictedAccess2009-10-01oai:cipf.fundanetsuite.com:p12312026-06-23T03:23:12ZpubrevCritical Role of TLR4 Response in the Activation of Microglia Induced by EthanolPascual, MGuerri, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1231info:doi:10.4049/jimmunol.0803590JOURNAL OF IMMUNOLOGYISSN: 00221767ISSNe: 15506606info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionMicroglial cells are the primary immune effector cells in the brain and play a pivotal role in the neuroinflammatory processes associated with a variety of neurological and pathological disorders. Alcohol consumption induces brain damage, although the neuropathological processes are poorly understood. We previously suggested that ethanol promotes inflammatory processes in the brain, up-regulating inflammatory mediators and signaling pathways associated with IIL-1RI/TLR4 receptors. In the present study we investigate whether ethanol induces microglia activation by stimulating TLR4 response and whether this response causes neuronal death and contributes to ethanol-induced neuroinflammatory damage. We demonstrate that ethanol activates microglia and stimulates NF-kappa B, MAPKs, and MyD88-independent (IFN regulatory factor-3, IFN-beta) pathways to trigger the production of inflammatory mediators, causing neuronal death. The inflammatory response induced by ethanol is completely abrogated in microglia of TLR4-deficient mice (TLR4(-/-)), thus supporting the role of these receptors in microglia activation and neuronal death. In accord with the in vitro findings, acute ethanol administration induces microglia activation (CD11b(+) cells) in cerebral cortex of TLR4(+/+) mice, but not in TLR4(-/-) mice. Taken together, our results not only provide the first evidence of the critical role of the TLR4 response in the ethanol-induced microglia activation, but also new insight into the basic mechanisms participating in ethanol-induced neuroinflammatory damage. The Journal of Immunology, 2009, 183: 4733-4744.OXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2009-10-01oai:cipf.fundanetsuite.com:p12322026-04-06T13:29:27ZpubrevINFLAMMATION AND HEPATIC ENCEPHALOPATHY: IBUPROFEN RESTORES LEARNING ABILITY AND MOTOR ACTIVITY IN RATS WITH CHRONIC LIVER FAILURERodrigo, RFelipo, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1232GLIAISSN: 08941491ISSNe: 10981136info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionWILEYenginfo:eu-repo/semantics/restrictedAccess2009-10-01oai:cipf.fundanetsuite.com:p12332026-03-24T12:10:10ZpubrevOn the Use of Functional Module Definitions in the Analysis of Genomic ExperimentsDopazo, Jhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1233Molecular & Cellular ToxicologyISSN: 1738642XISSNe: 20928467info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionKOREAN SOCIETY TOXICOGENOMICS & TOXICOPROTEOMICS-KSTTenginfo:eu-repo/semantics/restrictedAccess2009-09-20oai:cipf.fundanetsuite.com:p12342026-04-14T09:51:35ZpubrevGene expression profiling in rat cerebellum and striatum following in utero and lactational exposure to non-dioxin-like polychlorinated biphenylsDe Boever, PHollanders, KFelipo, VSchoeters, Ghttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1234info:doi:10.1016/j.toxlet.2009.06.827TOXICOLOGY LETTERSISSN: 03784274ISSNe: 18793169info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionELSEVIER IRELAND LTDenginfo:eu-repo/semantics/restrictedAccess2009-09-13oai:cipf.fundanetsuite.com:p12352026-03-24T12:10:10ZpubrevEffect of L-carnitine on postischemic inhibition of protein synthesis in the rat brainBurda, JViadel, MHDanielisova, VNemethova, MMontoliu, CFelipo, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1235info:doi:10.4149/gpb_2009_03_242GENERAL PHYSIOLOGY AND BIOPHYSICSISSN: 02315882ISSNe: 13384325info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe purpose of this study was to investigate effects of carnitine administration on protein synthesis recovery after transient cerebral ischemia. Rats received L-carnitine in two doses of 16 mmol/kg i.p. 15 min before ischemia and just on the onset of reperfusion. Transient forebrain ischemia was induced by 4-vessel occlusion for 15 min, followed by 30 min or 7 days of reperfusion. Protein synthesis rate, reinitiation ability and neurodegeneration in the frontal cortex and hippocampus were measured by the incorporation of radioactively labelled leucine into polypeptide chains in postmitochondrial supernatants and by Fluoro-Jade B staining.
A protective effect was observed, on protein synthesis as well as the number of surviving neurons, in the L-carnitine-treated groups. Our results indicate that L-carnitine can exert a protective effect in the development of reperfusion-induced injury. L-carnitine significantly reduced the ischemia/reperfusion-induced inhibition of translation and neurodegeneration in the neocortex as well as in the highly sensitive hippocampus and dorsolateral striatum. We expect that the ability of L-carnitine to keep translational machinery on facilitates efficacy of postischemic remodulation of gene expression.Ischemia; Protein synthesis; L-carnitine; HippocampusAEPRESS SROenginfo:eu-repo/semantics/restrictedAccess2009-09-01oai:cipf.fundanetsuite.com:p12362026-03-24T12:10:10ZpubrevFluorous TBAF: A Convenient and Selective Reagent for Fluoride-Mediated DeprotectionsFustero, SSancho, AGAcena, JLSanz-Cervera, JFhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1236info:doi:10.1021/jo901245mJOURNAL OF ORGANIC CHEMISTRYISSN: 00223263ISSNe: 15206904info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionA fluorous analogue of TBAF has been developed for its use in the clean removal of silicon-derived protecting groups. Purification of the crude mixtures by fluorous solid-phase extractions allowed alcohols, amines, and carboxylic acids to be obtained in high purity, with no need of chromatographic separations. The moderate reactivity of fluorous TBAF was exploited in selective deprotections of several bifunctional molecules.AMER CHEMICAL SOCenginfo:eu-repo/semantics/restrictedAccess2009-08-21oai:cipf.fundanetsuite.com:p12372026-04-06T13:29:27ZpubrevSynthesis and enzymatic evaluation of novel partially fluorinated thiol dual ACE/NEP inhibitorsOlimpieri, FTambaro, SFustero, SLazzari, PPani, LVolonterio, AZanda, Mhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1237info:doi:10.1016/j.bmcl.2009.06.064BIOORGANIC & MEDICINAL CHEMISTRY LETTERSISSN: 0960894XISSNe: 14643405info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionA novel family of peptidomimetics incorporating fluoroalkyl groups, mainly a trifluoromethyl, in alpha-position to a zinc(II)-binding thiol function, was synthesized in solution as well as in solid-phase. These compounds showed inhibitory potency in the nanomolar range against both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), whereas no inhibition of endothelin-converting enzyme-1 (ECE-1) was observed. The trifluoromethyl-derivatives were more potent than the parent unfluorinated analogues in the case of ACE, and less potent in the case of NEP. (C) 2009 Elsevier Ltd. All rights reserved.ACE inhibitors; NEP inhibitors; Fluorine; Zinc metallopeptidases; Michael reactionPERGAMON-ELSEVIER SCIENCE LTDenginfo:eu-repo/semantics/restrictedAccess2009-08-15oai:cipf.fundanetsuite.com:p12382026-04-06T13:29:27ZpubrevA Nanoconjugate Apaf-1 Inhibitor Protects Mesothelial Cells from Cytokine-Induced InjurySantamaria, BBenito-Martin, AUcero, ACAroeira, LSReyero, AVicent, MJOrzaez, MCeldran, AEsteban, JSelgas, RRuiz-Ortega, MCabrera, MLEgido, JOrtiz, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1238info:doi:10.1371/journal.pone.0006634PLoS OneISSN: 19326203info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionBackground: Inflammation may lead to tissue injury. We have studied the modulation of inflammatory milieu-induced tissue injury, as exemplified by the mesothelium. Peritoneal dialysis is complicated by peritonitis episodes that cause loss of mesothelium. Proinflammatory cytokines are increased in the peritoneal cavity during peritonitis episodes. However there is scarce information on the modulation of cell death by combinations of cytokines and on the therapeutic targets to prevent desmesothelization.
Methodology: Human mesothelial cells were cultured from effluents of stable peritoneal dialysis patients and from omentum of non-dialysis patients. Mesothelial cell death was studied in mice with S. aureus peritonitis and in mice injected with tumor necrosis factor alpha and interferon gamma. Tumor necrosis factor alpha and interferon gamma alone do not induce apoptosis in cultured mesothelial cells. By contrast, the cytokine combination increased the rate of apoptosis 2 to 3-fold over control. Cell death was associated with the activation of caspases and a pancaspase inhibitor prevented apoptosis. Specific caspase-8 and caspase-3 inhibitors were similarly effective. Co-incubation with both cytokines also impaired mesothelial wound healing in an in vitro model. However, inhibition of caspases did not improve wound healing and even impaired the long-term recovery from injury. By contrast, a polymeric nanoconjugate Apaf-1 inhibitor protected from apoptosis and allowed wound healing and long-term recovery. The Apaf-1 inhibitor also protected mesothelial cells from inflammation-induced injury in vivo in mice.
Conclusion: Cooperation between tumor necrosis factor alpha and interferon gamma contributes to mesothelial injury and impairs the regenerative capacity of the monolayer. Caspase inhibition attenuates mesothelial cell apoptosis but does not facilitate regeneration. A drug targeting Apaf-1 allows protection from apoptosis as well as regeneration in the course of inflammation-induced tissue injury.PUBLIC LIBRARY SCIENCEenginfo:eu-repo/semantics/restrictedAccess2009-08-13oai:cipf.fundanetsuite.com:p12392026-03-24T12:10:10ZlibpubSmart polymer nanocarriers for drug deliveryVicent, MJhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1239info:doi:10.1533/9780857097026.2.327ISBN: 9780857097026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionSmart polymeric nanocarriers are an important emerging area in drug delivery research. They are capable of releasing their payload in response to a specific stimulus, either present in the body or externally applied. We review the most important and extensively studied stimuli-responsive carriers, with special focus on their in vitro/in vivo preclinical evaluation. The most frequently studied stimuli include endogenous pH, enzymes and redox potential. Other emerging applications of externally applied stimuli such as temperature, magnetic field, ultrasound and light are also discussed. Finally, we close with an overall conclusion of the current state of the art and a look towards expected future breakthroughs using this type of nanocarrier.stimuli responsive; conjugate; micelle; nanoparticleWOODHEAD PUBL LTDenginfo:eu-repo/semantics/restrictedAccess2014-01-01oai:cipf.fundanetsuite.com:p12402026-06-19T03:32:25ZpubrevUnique Reactivity of Fluorinated Molecules with Transition MetalsCatalan, SMunoz, SBFustero, Shttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1240info:doi:10.2533/chimia.2014.382CHIMIAISSN: 00094293ISSNe: 26732424info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionOrganofluorine and organometallic chemistry by themselves constitute two potent areas in organic synthesis. Thus, the combination of both offers many chemical possibilities and represents a powerful tool for the design and development of new synthetic methodologies leading to diverse molecular structures in an efficient manner. Given the importance of the selective introduction of fluorine atoms into organic molecules and the effectiveness of transition metals in C C and C-heteroatom bond formation, this review represents an interesting read for this aim.Catalysis; Copper; Cross coupling; Fluorine; Gold; Metathesis; Pauson-Khand reaction; Silver; Transition metalSWISS CHEMICAL SOCenginfo:eu-repo/semantics/restrictedAccess2014-01-01oai:cipf.fundanetsuite.com:p12412026-04-06T13:29:27ZpubrevNew clicked thiirane derivatives as gelatinase inhibitors: the relevance of the P1 ' segmentFabre, BFilipiak, KCoderch, CZapico, JMPineda-Lucena, Ade Pascual-Teresa, BRamos, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1241info:doi:10.1039/c3ra46402dRSC AdvancesISSN: 20462069info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionGelatinases (MMP-2 and MMP-9), a subfamily of Matrix Metalloproteinases (MMPs), are involved in several pathologies and especially in cancer. Thiirane is a latent-zinc binding group used for the design of potent inhibitors of gelatinases. Here we report a new family of thiirane inhibitors, obtained by click chemistry. Thus, an azide fragment containing the thiirane group was connected to several lipophilic alkynes, which were designed to interact with the S1' pocket of the two gelatinases. Our hit compound (2f) displayed submicromolar inhibition of MMP-2 (IC50 = 0.62 mu M). Computational studies have been used to compare the binding mode of compound 2f in MMP-2 with the reference thiirane inhibitor (SB-3CT), allowing us to discuss the relevance of the P1' segment in order to maximize potency.ROYAL SOC CHEMISTRYenginfo:eu-repo/semantics/restrictedAccess2014-01-01oai:cipf.fundanetsuite.com:p12422026-03-24T12:10:10ZpubrevHepatic encephalopathy: effects of liver failure on brain functionFelipo, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1242info:doi:10.1038/nrn3587NATURE REVIEWS NEUROSCIENCEISSN: 1471003XISSNe: 14710048info:eu-repo/semantics/reviewinfo:eu-repo/semantics/publishedVersionLiver failure affects brain function, leading to neurological and psychiatric alterations; such alterations are referred to as hepatic encephalopathy (HE). Early diagnosis of minimal HE reveals an unexpectedly high incidence of mild cognitive impairment and psychomotor slowing in patients with liver cirrhosis - conditions that have serious health, social and economic consequences. The mechanisms responsible for the neurological alterations in HE are beginning to emerge. New therapeutic strategies acting on specific targets in the brain (phosphodiesterase 5, type A GABA receptors, cyclooxygenase and mitogen-activated protein kinase p38) have been shown to restore cognitive and motor function in animal models of chronic HE, and NMDA receptor antagonists have been shown to increase survival in acute liver failure. This article reviews the latest studies aimed at understanding how liver failure affects brain function and potential ways to ameliorate these effects.NATURE PORTFOLIOenginfo:eu-repo/semantics/restrictedAccess2013-12-01oai:cipf.fundanetsuite.com:p12432026-04-06T13:29:27ZpubrevTemperature-controlled release by changes in the secondary structure of peptides anchored onto mesoporous silica supportsde la Torre, CAgostini, AMondragon, LOrzaez, MSancenon, FMartinez-Manez, RMarcos, MDAmoros, Phttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1243info:doi:10.1039/c3cc49421gCHEMICAL COMMUNICATIONSISSN: 13597345ISSNe: 1364548Xinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionChanges in the conformation of a peptide anchored onto the external surface of mesoporous silica nanoparticles have been used to design novel temperature-controlled delivery systems.ROYAL SOC CHEMISTRYenginfo:eu-repo/semantics/restrictedAccess2014-01-01oai:cipf.fundanetsuite.com:p12442026-03-24T12:10:10ZpubrevTungstate promotes beta-cell survival in Irs2(-/-) miceOliveira, JMRebuffat, SAGasa, RBurks, DJGarcia, AKalko, SGZafra, DGuinovart, JJGomis, Rhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1244info:doi:10.1152/ajpendo.00409.2013AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISMISSN: 01931849ISSNe: 15221555info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPancreatic beta-cells play a central role in type 2 diabetes (T2D) development, which is characterized by the progressive decline of the functional beta-cell mass that is associated mainly with increased beta-cell apoptosis. Thus, understanding how to enhance survival of beta-cells is key for the management of T2D. The insulin receptor substrate-2 (IRS-2) protein is pivotal in mediating the insulin/IGF signaling pathway in beta-cells. In fact, IRS-2 is critically required for beta-cell compensation in conditions of increased insulin demand and for beta-cell survival. Tungstate is a powerful antidiabetic agent that has been shown to promote beta-cell recovery in toxininduced diabetic rodent models. In this study, we investigated whether tungstate could prevent the onset of diabetes in a scenario of dysregulated insulin/IGF signaling and massive beta-cell death. To this end, we treated mice deficient in IRS2 (Irs2(-/-)), which exhibit severe beta-cell loss, with tungstate for 3 wk. Tungstate normalized glucose tolerance in Irs(2)(-/-) mice in correlation with increased beta-cell mass, increased beta-cell replication, and a striking threefold reduction in beta-cell apoptosis. Islets from treated Irs(2)(-/-) exhibited increased phosphorylated Erk1/2. Interestingly, tungstate repressed apoptosis-related genes in Irs(2)(-/-) islets in vitro, and ERK1/2 blockade abolished some of these effects. Gene expression profiling showed evidence of a broad impact of tungstate on cell death pathways in islets from Irs(2)(-/-) mice, consistent with reduced apoptotic rates. Our results support the finding that beta-cell death can be arrested in the absence of IRS2 and that therapies aimed at reversing beta-cell mass decline are potential strategies to prevent the progression to T2D.type 2 diabetes; beta-cell loss; apoptosis; islet; tungstate; insulin receptor substrate-2; extracellular signal; regulated kinase 1/2AMER PHYSIOLOGICAL SOCenginfo:eu-repo/semantics/restrictedAccess2014-01-01oai:cipf.fundanetsuite.com:p12452026-06-23T03:23:12ZpubrevPerspectives and Future Directions of Human Pluripotent Stem Cell-Based Therapies: Lessons from Geron's Clinical Trial for Spinal Cord InjuryLukovic, DStojkovic, MMoreno-Manzano, VBhattacharya, SSErceg, Shttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1245info:doi:10.1089/scd.2013.0266STEM CELLS AND DEVELOPMENTISSN: 15473287ISSNe: 15578534info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionHalting the first clinical trial on the use of embryonic stem cell derivatives for spinal cord injury resulted in disappointment and created concerns about the future use of pluripotent stem cell-based therapy in the treatment of human diseases. This article presents reflections and concerns related to the halted embryonic stem cell-based clinical trial and discusses some important and controversial issues for achieving safe and successful cell therapy. This manuscript highlights two important points for successful translation of pluripotent stem cell-based therapy in clinics: (i) reproducible xeno-free growth and differentiation of pluripotent stem cells in good manufacturing practice conditions as the prerequisites to ensure a defined and controlled cell source and (ii) extensive studies in small and large animal models and comprehensive basic studies to determine any adverse or toxic effects of transplanted cells, especially teratoma formation, in addition to improving surgical procedure and cell delivery system.SAGE PUBLICATIONS INCenginfo:eu-repo/semantics/restrictedAccess2014-01-01oai:cipf.fundanetsuite.com:p12462026-04-06T13:29:27ZpubrevPTEN Increases Autophagy and Inhibits the Ubiquitin-Proteasome Pathway in Glioma Cells Independently of its Lipid Phosphatase ActivityAguado, CLoutfi, MKnecht, Ehttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1246info:doi:10.1371/journal.pone.0083318PLoS OneISSN: 19326203info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionTwo major mechanisms of intracellular protein degradation, autophagy and the ubiquitin-proteasome pathway, operate in mammalian cells. PTEN, which is frequently mutated in glioblastomas, is a tumor suppressor gene that encodes a dual specificity phosphatase that antagonizes the phosphatidylinositol 3-kinase class I/AKT/mTOR pathway, which is a key regulator of autophagy. Here, we investigated in U87MG human glioma cells the role of PTEN in the regulation of autophagy and the ubiquitin-proteasome pathway, because both are functionally linked and are relevant in cancer progression. Since U87MG glioma cells lack a functional PTEN, we used stable clones that express, under the control of a tetracycline-inducible system (Tet-on), wild-type PTEN and two of its mutants, G129E-PTEN and C124S-PTEN, which, respectively, lack the lipid phosphatase activity only and both the lipid and the protein phosphatase activities of this protein. Expression of PTEN in U87MG glioma cells decreased proteasome activity and also reduced protein ubiquitination. On the contrary, expression of PTEN increased the autophagic flux and the lysosomal mass. Interestingly, and although PTEN negatively regulates the phosphatidylinositol 3-kinase class I/AKT/mTOR signaling pathway by its lipid phosphatase activity, both effects in U87MG cells were independent of this activity. These results suggest a new mTOR-independent signaling pathway by which PTEN can regulate in opposite directions the main mechanisms of intracellular protein degradation.PUBLIC LIBRARY SCIENCEenginfo:eu-repo/semantics/restrictedAccess2013-12-13oai:cipf.fundanetsuite.com:p12472026-04-06T13:29:27ZpubrevStructure-Based Design of an RNA-Binding p-Terphenylene Scaffold that Inhibits HIV-1 Rev Protein FunctionGonzalez-Bulnes, LIbanez, IBedoya, LMBeltran, MCatalan, SAlcami, JFustero, SGallego, Jhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1247info:doi:10.1002/anie.201306665ANGEWANDTE CHEMIE-INTERNATIONAL EDITIONISSN: 14337851ISSNe: 15213773info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiondrug design; HIV; RNA; small-molecule inhibitors; terphenylsWILEY-V C H VERLAG GMBHenginfo:eu-repo/semantics/restrictedAccess2013-12-09oai:cipf.fundanetsuite.com:p12482026-04-06T13:29:27ZpubrevMetabolomic Profile of Umbilical Cord Blood Plasma from Early and Late Intrauterine Growth Restricted (IUGR) Neonates with and without Signs of Brain VasodilationSanz-Cortes, MCrispi, FFigueras, FPineda-Lucena, AGratacos, Ehttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1248info:doi:10.1371/journal.pone.0080121PLoS OneISSN: 19326203info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionObjectives: To characterize via NMR spectroscopy the full spectrum of metabolic changes in umbilical vein blood plasma of newborns diagnosed with different clinical forms of intrauterine growth restriction (IUGR).
Methods: 23 early IUGR cases and matched 23 adequate-for-gestational-age (AGA) controls and 56 late IUGR cases with 56 matched AGAs were included in this study. Early IUGR was defined as a birth weight <10th centile, abnormal umbilical artery (UA) Doppler and delivery <35 weeks. Late IUGR was defined as a birth weight <10th centile with normal UA Doppler and delivery >= 35 weeks. This group was subdivided in 18 vasodilated (VD) and 38 non-VD late IUGR fetuses. All AGA patients had a birth weight >10th centile. H-1 nuclear magnetic resonance (NMR) metabolomics of the blood samples collected from the umbilical vein at delivery was obtained. Multivariate statistical analysis identified several metabolites that allowed the discrimination between the different IUGR subgroups, and their comparative levels were quantified from the NMR data.
Results: The NMR-based analysis showed increased unsaturated lipids and VLDL levels in both early and late IUGR samples, decreased glucose and increased acetone levels in early IUGR. Non-significant trends for decreased glucose and increased acetone levels were present in late IUGR, which followed a severity gradient when the VD and non-VD subgroups were considered. Regarding amino acids and derivatives, early IUGR showed significantly increased glutamine and creatine levels, whereas the amounts of phenylalanine and tyrosine were decreased in early and late-VD IUGR samples. Valine and leucine were decreased in late IUGR samples. Choline levels were decreased in all clinical subforms of IUGR.
Conclusions: IUGR is not associated with a unique metabolic profile, but important changes are present in different clinical subsets used in research and clinical practice. These results may help in characterizing comprehensively specific alterations underlying different IUGR subsets.PUBLIC LIBRARY SCIENCEenginfo:eu-repo/semantics/restrictedAccess2013-12-02oai:cipf.fundanetsuite.com:p12492026-06-19T03:32:25ZpubrevAutophagy activation by hidrogen sulfide protects cardiomiocytes of death by starvationGarcia, NAMoncayo, JAguado, CMarti, NKnecht, EDiez, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1249HUMAN GENE THERAPYISSN: 10430342ISSNe: 15577422info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionSAGE PUBLICATIONS INCenginfo:eu-repo/semantics/restrictedAccess2013-12-01oai:cipf.fundanetsuite.com:p12502026-03-24T12:10:10ZpubrevLafora disease fibroblasts exemplify the molecular interdependence between thioredoxin 1 and the proteasome in mammalian cellsGarcia-Gimenez, JLSeco-Cervera, MAguado, CRoma-Mateo, CDasi, FPriego, SMarkovic, JKnecht, ESanz, PPallardo, FVhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1250info:doi:10.1016/j.freeradbiomed.2013.07.001FREE RADICAL BIOLOGY AND MEDICINEISSN: 08915849ISSNe: 18734596info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThioredoxin 1 (Trx1) is a key regulator of cellular redox balance and participates in cellular signaling events. Recent evidence from yeast indicates that members of the Trx family interact with the 20S proteasome, indicating redox regulation of proteasome activity. However, there is little information about the interrelationship of Trx proteins with the proteasome system in mammalian cells, especially in the nucleus. Here, we have investigated this relationship under various cellular conditions in mammalian cells. We show that Trx1 levels and its subcellular localization (cytosol, endoplasmic reticulum, and nucleus) depend on proteasome activity during the cell cycle in NIH3T3 fibroblasts and under stress conditions, when proteasomes are inhibited. In addition, we also studied in these cells how the main cellular antioxidant systems are stimulated when proteasome activity is inhibited. Finally, we describe a reduction in Trx1 levels in Lafora disease fibroblasts and demonstrate that the nuclear colocalization of Trx1 with 20S proteasomes in laforin-deficient cells is altered compared with control cells. Our results indicate a close relationship between Trx1 and the 20S nuclear proteasome and give a new perspective to the study of diseases or physiopathological conditions in which defects in the proteasome system are associated with oxidative stress. (C) 2013 Elsevier Inc. All rights reserved.Thioredoxin 1; Proteasome; Cell proliferation; Lafora disease; Antioxidant enzymes; Rare diseases; Free radicalsELSEVIER SCIENCE INCenginfo:eu-repo/semantics/restrictedAccess2013-12-01oai:cipf.fundanetsuite.com:p12512026-03-24T12:10:10ZpubrevIntrauterine growth restriction is associated with cardiac ultrastructural and gene expression changes related to the energetic metabolism in a rabbit modelGonzalez-Tendero, ATorre, IGarcia-Canadilla, PCrispi, FGarcia-Garcia, FDopazo, JBijnens, BGratacos, Ehttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1251info:doi:10.1152/ajpheart.00514.2013AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGYISSN: 03636135ISSNe: 15221539info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionIntrauterine growth restriction (IUGR) affects 7-10% of pregnancies and is associated with cardiovascular remodeling and dysfunction, which persists into adulthood. The underlying subcellular remodeling and cardiovascular programming events are still poorly documented. Cardiac muscle is central in the fetal adaptive mechanism to IUGR given its high energetic demands. The energetic homeostasis depends on the correct interaction of several molecular pathways and the adequate arrangement of intracellular energetic units (ICEUs), where mitochondria interact with the contractile machinery and the main cardiac ATPases to enable a quick and efficient energy transfer. We studied subcellular cardiac adaptations to IUGR in an experimental rabbit model. We evaluated the ultrastructure of ICEUs with transmission electron microscopy and observed an altered spatial arrangement in IUGR, with significant increases in cytosolic space between mitochondria and myofilaments. A global decrease of mitochondrial density was also observed. In addition, we conducted a global gene expression profile by advanced bioinformatics tools to assess the expression of genes involved in the cardiomyocyte energetic metabolism and identified four gene modules with a coordinated over-representation in IUGR: oxygen homeostasis (GO: 0032364), mitochondrial respiratory chain complex I (GO: 0005747), oxidative phosphorylation (GO:0006119), and NADH dehydrogenase activity (GO: 0003954). These findings might contribute to changes in energetic homeostasis in IUGR. The potential persistence and role of these changes in long-term cardiovascular programming deserves further investigation.cardiomyocyte intracellular organization; energetic metabolism; fetal cardiac programming; intracellular energetic units; intrauterine growth restrictionAMER PHYSIOLOGICAL SOCenginfo:eu-repo/semantics/restrictedAccess2013-12-01oai:cipf.fundanetsuite.com:p12522026-03-31T07:51:06ZpubrevPathways systematically associated to Hirschsprung's diseaseFernandez, RMBleda, MLuzon-Toro, BGarcia-Alonso, LArnold, SSribudiani, YBesmond, CLantieri, FDoan, BCeccherini, ILyonnet, SHofstra, RMWChakravarti, AAntinolo, GDopazo, JBorrego, Shttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1252info:doi:10.1186/1750-1172-8-187Orphanet Journal of Rare DiseasesISSN: 17501172info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionDespite it has been reported that several loci are involved in Hirschsprung's disease, the molecular basis of the disease remains yet essentially unknown. The study of collective properties of modules of functionally-related genes provides an efficient and sensitive statistical framework that can overcome sample size limitations in the study of rare diseases. Here, we present the extension of a previous study of a Spanish series of HSCR trios to an international cohort of 162 HSCR trios to validate the generality of the underlying functional basis of the Hirschsprung's disease mechanisms previously found. The Pathway-Based Analysis (PBA) confirms a strong association of gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other processes related to the disease. In addition, network analysis recovers sub-networks significantly associated to the disease, which contain genes related to the same functionalities, thus providing an independent validation of these findings. The functional profiles of association obtained for patients populations from different countries were compared to each other. While gene associations were different at each series, the main functional associations were identical in all the five populations. These observations would also explain the reported low reproducibility of associations of individual disease genes across populations.BMCenginfo:eu-repo/semantics/restrictedAccess2013-12-02oai:cipf.fundanetsuite.com:p12532026-06-19T03:32:25ZpubrevDevelopment of bioengineered skin-humanized mouse models for inflammatory skin diseasesCarretero, MGuerrero-Aspizua, SIllera, NDuarte, BHolguin, ARetamosa, LNavarro, MGarcia, FDOPAZO, JOAQUINLarcher, Fdel Rio, Mhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1253HUMAN GENE THERAPYISSN: 10430342ISSNe: 15577422info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionSAGE PUBLICATIONS INCenginfo:eu-repo/semantics/restrictedAccess2013-12-01oai:cipf.fundanetsuite.com:p12542026-03-24T12:10:10ZpubrevEXPRESSION OF STEMNESS FACTORS OCT4 AND NANOG IN RESECTABLE NON-SMALL CELL LUNG CANCER.Requena, RLewintre, EJLucas, RFarras, RMartorell, MUso, MGallach, SBlasco, ACamps, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1254Journal of Thoracic OncologyISSN: 15560864ISSNe: 15561380info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionOCT4; NANOG; early-stage NSCLC; biomarkerELSEVIER SCIENCE INCenginfo:eu-repo/semantics/restrictedAccess2013-11-01oai:cipf.fundanetsuite.com:p12552026-03-24T12:10:10ZpubrevAn Approach to 2,4-Substituted Pyrazolo[1,5-a]pyridines and Pyrazolo[1,5-a]azepines by Ring-Closing MetathesisFustero, SRoman, RAsensio, AMaestro, MAAcena, JLSimon-Fuentes, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1255info:doi:10.1002/ejoc.201300901EUROPEAN JOURNAL OF ORGANIC CHEMISTRYISSN: 1434193XISSNe: 10990690info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe ring-closing metathesis (RCM) reactions of dienylpyrazoles have been employed in the synthesis of pyrazolo[1,5-a]pyridine and pyrazolo[1,5-a]azepine derivatives. Based on this approach, the diastereoselective synthesis of potential peptidomimetics containing four amino acid residues with the second (i+1) and third (i+2) fragments having been substituted by bicyclic frameworks is described.Synthetic methods; Asymmetric synthesis; Metathesis; Peptidomimetics; Nitrogen heterocyclesWILEY-V C H VERLAG GMBHenginfo:eu-repo/semantics/restrictedAccess2013-11-01oai:cipf.fundanetsuite.com:p12562026-03-24T12:10:10ZpubrevSerum nitrotyrosine and psychometric tests as indicators of impaired fitness to drive in cirrhotic patients with minimal hepatic encephalopathyFelipo, VUrios, AValero, PSanchez, MSerra, MAPareja, IRodriguez, FGimenez-Garzo, CSanmartin, JMontoliu, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1256info:doi:10.1111/liv.12206LIVER INTERNATIONALISSN: 14783223ISSNe: 14783231info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionBackground & Aims Cirrhotic patients with minimal hepatic encephalopathy (MHE) show impaired driving ability and increased vehicle accidents. The neurological deficits contributing to impair driving and the underlying mechanisms are poorly understood. Early detection of driving impairment would help to reduce traffic accidents in MHE patients. It would be therefore useful to have psychometric or biochemical parameters reflecting driving impairment. The aims of this work were as follows: (i) to shed light on the neurological deficits contributing to impair driving; (ii) to assess whether some psychometric test or biochemical parameter is a good indicator of driving impairment.MethodsWe assessed in 22 controls, 36 cirrhotic patients without and 15 with MHE, driving performance using a driving simulator (SIMUVEG) and Driver Test. MHE was diagnosed using the psychometric hepatic encephalopathy score (PHES). Psychometric tests assessing different neurological functions (mental processing speed, attention, visuo-spatial and bimanual coordination) were performed. Blood ammonia and parameters related with nitric oxide-cGMP metabolism, IL-6, IL-18 and 3-nitrotyrosine were measured.ResultsPatients with MHE showed impaired driving ability correlating with MHE grade, with impaired vehicle lateral control in spite of reduced driving speed. Patients with MHE show psychomotor slowing, longer reaction times, impaired bimanual and visuo-spatial coordination and concentrated attention and slowed speed of anticipation and increased blood ammonia, cGMP, IL-6, IL-18 and 3nitrotyrosine.Conclusions Impaired mental processing speed, attention and alterations in visuo-spatial and motor coordination seem main contributors to impaired driving ability in patients with MHE. Increased serum 3-nitrotyrosine is associated with impaired driving ability.3-nitrotyrosine; fitness to drive; minimal hepatic encephalopathy; psychometric testsWILEYenginfo:eu-repo/semantics/restrictedAccess2013-11-01oai:cipf.fundanetsuite.com:p12572026-04-06T13:29:27ZpubrevProgress towards water-soluble triazole-based selective MMP-2 inhibitorsFabre, BFilipiak, KZapico, JMDiaz, NMartinez-Alcazar, MPSuarez, DPineda-Lucena, ARamos, Ade Pascual-Teresaa, Bhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1257info:doi:10.1039/c3ob41046cORGANIC & BIOMOLECULAR CHEMISTRYISSN: 14770520ISSNe: 14770539info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionWater solubility is a key aspect that needs to be addressed to obtain drug-like compounds. In an effort to improve the water solubility of our recently reported nanomolar matrix metalloproteinase type 2 (MMP-2) inhibitors based on triazole-substituted hydroxamates, we synthesized a new series of alpha-sulfone, alpha-tetrahydropyran and alpha-piperidine, alpha-sulfone clicked hydroxamates and determined their inhibitory activities against both MMP-2 and MMP-9. The best results were found for 13e, a water-soluble compound that displays a low nanomolar activity against MMP-2 and is 26-fold less active against MMP-9. This finding allowed us to pursue in vitro permeability through the Caco-2 monolayer and opened the possibility of carrying out further preclinical investigations. Docking and MD simulations have been performed in order to rationalize the biological results. The inhibitory activity of this compound against a panel of ten MMPs was determined showing an interesting MMP-2/MMP-1, -8, and -14 selectivity profile. The cytotoxicity and anti-invasive activity of the compounds on highly metastatic human fibrosarcoma tumor cells (HT1080) were determined, showing, at 10 mu M concentration, a decrease in cell invasiveness up to 80%.ROYAL SOC CHEMISTRYenginfo:eu-repo/semantics/restrictedAccess2013-10-14oai:cipf.fundanetsuite.com:p12582026-04-06T13:29:27ZpubrevTargeting Neuroblastoma Stem Cells with Retinoic Acid and Proteasome InhibitorHammerle, BYanez, YPalanca, SCanete, ABurks, DJCastel, Vde Mora, JFhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1258info:doi:10.1371/journal.pone.0076761PLoS OneISSN: 19326203info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionBackground: Neuroblastma cell lines contain a side-population of cells which express stemness markers. These stem-like cells may represent the potential underlying mechanism for resistance to conventional therapy and recurrence of neuroblastoma in patients.
Methodology/Principal Findings: To develop novel strategies for targeting the side-population of neurobastomas, we analyzed the effects of 13-cis-retinoic acid (RA) combined with the proteasome inhibitor MG132. The short-term action of the treatment was compared with effects after a 5-day recovery period during which both chemicals were withdrawn. RA induced growth arrest and differentiation of SH-SY5Y and SK-N-BE(2) neuroblastoma cell lines. Inhibition of the proteasome caused apoptosis in both cell lines, thus, revealing the critical role of this pathway in the regulated degradation of proteins involved in neuroblastoma proliferation and survival. The combination of RA with MG132 induced apoptosis in a dose-dependent manner, in addition to promoting G2/M arrest in treated cultures. Interestingly, expression of stem cell markers such as Nestin, Sox2, and Oct4 were reduced after the recovery period of combined treatment as compared with untreated cells or treated cells with either compound alone. Consistent with this, neurosphere formation was significantly impaired by the combined treatment of RA and MG132.
Conclusions: Given that stem-like cells are associated with resistant to conventional therapy and are thought to be responsible for relapse, our results suggest that dual therapy of RA and proteasome inhibitor might be beneficial for targeting the side-population of cells associated residual disease in high-risk neuroblastoma.PUBLIC LIBRARY SCIENCEenginfo:eu-repo/semantics/restrictedAccess2013-10-07oai:cipf.fundanetsuite.com:p12592026-04-06T13:29:27ZpubrevMammosphere Formation in Breast Carcinoma Cell Lines Depends upon Expression of E-cadherinIglesias, JMBeloqui, IGarcia-Garcia, FLeis, OVazquez-Martin, AEguiara, ACufi, SPavon, AMenendez, JADopazo, JMartin, AGhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1259info:doi:10.1371/journal.pone.0077281PLoS OneISSN: 19326203info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionTumors are heterogeneous at the cellular level where the ability to maintain tumor growth resides in discrete cell populations. Floating sphere-forming assays are broadly used to test stem cell activity in tissues, tumors and cell lines. Spheroids are originated from a small population of cells with stem cell features able to grow in suspension culture and behaving as tumorigenic in mice. We tested the ability of eleven common breast cancer cell lines representing the major breast cancer subtypes to grow as mammospheres, measuring the ability to maintain cell viability upon serial non-adherent passage. Only MCF7, T47D, BT474, MDA-MB-436 and JIMT1 were successfully propagated as long-term mammosphere cultures, measured as the increase in the number of viable cells upon serial non-adherent passages. Other cell lines tested (SKBR3, MDA-MB-231, MDA-MB-468 and MDA-MB-435) formed cell clumps that can be disaggregated mechanically, but cell viability drops dramatically on their second passage. HCC1937 and HCC1569 cells formed typical mammospheres, although they could not be propagated as long-term mammosphere cultures. All the sphere forming lines but MDA-MB-436 express E-cadherin on their surface. Knock down of E-cadherin expression in MCF-7 cells abrogated its ability to grow as mammospheres, while re-expression of E-cadherin in SKBR3 cells allow them to form mammospheres. Therefore, the mammosphere assay is suitable to reveal stem like features in breast cancer cell lines that express E-cadherin.PUBLIC LIBRARY SCIENCEenginfo:eu-repo/semantics/restrictedAccess2013-10-04oai:cipf.fundanetsuite.com:p12602026-03-24T12:10:10ZpubrevInsulin is required for the differentiation and proliferation of hepatocyte progenitor cells in vitro: A novel role for insulin receptor substrate 2Noon, LAMartinez-Romero, AO'Connor, JECorlu, ABouille, PGuillouzco, CBurks, DJhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1260HEPATOLOGYISSN: 02709139ISSNe: 15273350info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionLIPPINCOTT WILLIAMS & WILKINSenginfo:eu-repo/semantics/restrictedAccess2013-10-01oai:cipf.fundanetsuite.com:p12612026-03-24T12:10:10ZpubrevOpen innovation drug discovery: An example of symbiotic industry-academia collaborationNavarro, AFustero, SRoman, RPineiro-Nunez, MAlvim-Gaston, MHusain, SUhlik, MPulley, SRLee, JSall, DWodka, DClay, JMhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1261Abstracts Of Papers Of The American Chemical SocietyISSN: 00657727info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionAMER CHEMICAL SOCenginfo:eu-repo/semantics/restrictedAccess2013-09-08oai:cipf.fundanetsuite.com:p12622026-03-24T12:10:10ZpubrevGender differences in alcohol-induced neurotoxicity and brain damageAlfonso-Loeches, SPascual, MGuerri, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1262info:doi:10.1016/j.tox.2013.03.001TOXICOLOGYISSN: 0300483XISSNe: 18793185info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionConsiderable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1 beta, TNF-alpha), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse. (C) 2013 Elsevier Ireland Ltd. All rights reserved.TLR4; Alcohol; Gender differences; Neuroinflammation; Brain damageELSEVIER IRELAND LTDenginfo:eu-repo/semantics/restrictedAccess2013-09-06oai:cipf.fundanetsuite.com:p12632026-03-24T12:10:10ZpubrevGender differential effects of developmental exposure to methyl-mercury, polychlorinated biphenyls 126 or 153, or its combinations on motor activity and coordinationLlansola, MFelipo, Vhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1263info:doi:10.1016/j.tox.2012.11.016TOXICOLOGYISSN: 0300483XISSNe: 18793185info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPolychlorinated biphenyls (PCBs) and methylmercury (MeHg) are persistent organic pollutants accumulating in the food chain. Pre- and neonatal exposure to these neurotoxicants may affect brain development and lead to long-lasting alterations in cerebral function, which can result in motor alterations in youth and/or adulthood. Some neurotoxicants induce gender specific effects.
The aims of the present work were to: (1) assess the effects of developmental exposure to MeHg, PCB 153 or PCB 126 on spontaneous locomotor and vertical activity and motor coordination when the rats are 2-month old; (2) assess whether perinatal exposure to combinations of MeHg with PCB153 or PCB126 alter the effects of the individual neurotoxicants; (3) follow the progression of motor alterations when the rats are 3-, 5- and 7-month old; (4) assess if the effects are similar or different in males and females.
Pregnant rats were treated with MeHg (0.5 mg/kg day); PCB126 (100 ng/kg day) or PCB153 (1 mg/kg day) or with combinations of MeHg with each PCB, administered in food from gestational day 7 until weaning at post-natal day 21.
PCB 126 impaired motor coordination at 2 months in males but not in females. PCB 153 impaired coordination both in males and females. Combinations of MeHg with PCB153 or PCB126 did not affect motor coordination, indicating that MeHg counteracts the effects of the PBCs.
The combination of MeHg and PCB153 induces hypolocomotion at 2 months but hyperactivity at 7 months while the individual compounds did not induce any effect. PCB126 induced gender selective effects, reducing locomotor activity at 2 months in females but not in males. The combination of MeHg and PCB126 behaves as PCB126 alone.
All compounds and combinations tested induce gender-selective alterations in vertical activity. The effects on locomotor and vertical activity change with age in the same rats. At 2 months all compounds and combinations reduce vertical activity in females but not in males. At 7 months all treatments induced hyperactivity both in males and females, except MeHg+PCB126.
In conclusion, the results show that: (a) many motor alterations induced by most compounds are different in males and females; (b) mixtures of MeHg with PCBs 153 or 126 induce different effects that the individual compounds; (c) different types of motor activity (spontaneous locomotion, vertical activity and motor coordination) are affected differently by the same neurotoxicant or mixture; and (d) the effects on locomotor and specially on vertical activity change with the age of the rat. Most compounds reduce activity at youth (2 months) and induce hyperactivity at adulthood (5-7 months). The change from hypo-to hyperactivity occurs earlier in males. (C) 2012 Elsevier Ireland Ltd. All rights reserved.Methyl mercury; Polychlorinated biphenyls; Motor activity; Motor coordination; Gender difference; Developmental neurotoxicityELSEVIER IRELAND LTDenginfo:eu-repo/semantics/restrictedAccess2013-09-06oai:cipf.fundanetsuite.com:p12642026-03-24T12:10:10ZpubrevDopamine could be involved in the maintenance of rat pancreatic beta cells controlling insulin secretion and cellular proliferationGarcia-Barrado, MJBlanco, EJIglesias-Osma, MCCarretero-Hernandez, MBurks, DJCarretero, Jhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1264DIABETOLOGIAISSN: 0012186XISSNe: 14320428info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionSPRINGERenginfo:eu-repo/semantics/restrictedAccess2013-09-01oai:cipf.fundanetsuite.com:p12652026-03-24T12:10:10ZpubrevInfluence of olive pollen stimuli on the gene- expression profile in allergic patientsCalzada, DAguerri, MBaos, SMata, MDopazo, JLahoz, CCardaba, Bhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1265ALLERGYISSN: 01054538ISSNe: 13989995info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionWILEYenginfo:eu-repo/semantics/restrictedAccess2013-09-01oai:cipf.fundanetsuite.com:p12662026-03-24T12:10:10ZpubrevMultiple Myeloma Patients Have a Specific Serum Metabolomic Profile That Changes after Achieving Complete RemissionPuchades-Carrasco, LLecumberri, RMartinez-Lopez, JLahuerta, JJMateos, MVProsper, FSan-Miguel, JFPineda-Lucena, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1266info:doi:10.1158/1078-0432.CCR-12-2917CLINICAL CANCER RESEARCHISSN: 10780432ISSNe: 15573265info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPurpose: Multiple myeloma remains an incurable disease. New approaches to develop better tools for improving patient prognostication and monitoring treatment efficacy are very much needed. In this study, we aimed to evaluate the potential of metabolomics by H-1-NMR to provide information on metabolic profiles that could be useful in the management of multiple myeloma.
Experimental Design: Serum samples were collected from multiple myeloma patients at the time of diagnosis and after achieving complete remission. A matched control set of samples was also included in the study. The H-1-NMR measurements used to obtain the metabolic profile for each patient were followed by the application of univariate and multivariate statistical analyses to determine significant differences.
Results: Metabolic profiles of multiple myeloma patients at diagnosis exhibited higher levels of isoleucine, arginine, acetate, phenylalanine, and tyrosine, and decreased levels of 3-hydroxybutyrate, lysine, glutamine, and some lipids compared with the control set. A similar analysis conducted in multiple myeloma patients after achieving complete remission indicated that some of the metabolic changes (i.e., glutamine, cholesterol, lysine) observed at diagnosis displayed a variation in the opposite direction upon responding to treatment, thus contributing to multiple myeloma patients having a closer metabolic profile to those of healthy individuals after the disappearance of major disease manifestations.
Conclusions: The results highlight the potential of metabolic profiles obtained by H-1-NMR in identifying multiple myeloma biomarkers that may be useful to objectively discriminate individuals with and without multiple myeloma, and monitor response to treatment. (C)2013 AACR.AMER ASSOC CANCER RESEARCHenginfo:eu-repo/semantics/restrictedAccess2013-09-01oai:cipf.fundanetsuite.com:p12672026-03-24T12:10:10ZpubrevETHANOL ALTERS HUMAN EMBRYONIC STEM CELLS DIFFERENTIATION TOWARD NEURAL PROGENITORS (NPS), ALTERS CELL FATE AND IMPAIRS NPS TRANSFORMATION INTO MATURE NEURAL CELLSGuerri, CVisconti, RKostic, Jhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1267ALCOHOL AND ALCOHOLISMISSN: 07350414ISSNe: 14643502info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2013-09-01oai:cipf.fundanetsuite.com:p12682026-03-24T12:10:10ZpubrevLONG-TERM COGNITIVE DYSFUNCTIONS IN ADOLESCENT RATS WITH BINGE DRINKING ARE ASSOCIATED WITH NEUROIMMUNE ACTIVATION AND MYELIN DYSFUNCTIONGuerri, CPascual, MPla, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1268ALCOHOL AND ALCOHOLISMISSN: 07350414ISSNe: 14643502info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2013-09-01oai:cipf.fundanetsuite.com:p12692026-03-24T12:10:10ZpubrevDYSFUNCTIONS IN PROTEIN DEGRADATION IN ALCOHOL-INDUCED NEUROINFLAMMATION AND BRAIN DAMAGEPascual-Mora, MPla, ARenau-Piqueras, JGuerri, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1269ALCOHOL AND ALCOHOLISMISSN: 07350414ISSNe: 14643502info:eu-repo/semantics/conferenceObjectMeeting Abstractinfo:eu-repo/semantics/publishedVersionOXFORD UNIV PRESSenginfo:eu-repo/semantics/restrictedAccess2013-09-01oai:cipf.fundanetsuite.com:p12702026-03-24T12:10:10ZpubrevOne-pot cross-enyne metathesis (CEYM)-Diels-Alder reaction of gem-difluoropropargylic alkynesFustero, SBello, PMiro, JHaufe, Gdel Pozo, Chttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1270info:doi:10.3762/bjoc.9.305Beilstein Journal of Organic ChemistryISSN: 18605397info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPropargylic difluorides 1 were used as starting substrates in a combination of cross-enyne metathesis and Diels-Alder reactions. Thus, the reaction of 1 with ethylene in the presence of 2nd generation Hoveyda-Grubbs catalyst generates a diene moiety which in situ reacts with a wide variety of dienophiles giving rise to a small family of new fluorinated carbo-and heterocyclic derivatives in moderate to good yields. This is a complementary protocol to the one previously described by our research group, which involved the use of 1,7-octadiene as an internal source of ethylene.cross metathesis; Diels-Alder; one-pot reaction; organo-fluorine; propargylic difluoridesBEILSTEIN-INSTITUTenginfo:eu-repo/semantics/restrictedAccess2013-11-28oai:cipf.fundanetsuite.com:p12712026-03-24T12:10:10ZpubrevWhole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosaMendez-Vidal, CGonzalez-del Pozo, MVela-Boza, ASantoyo-Lopez, JLopez-Domingo, FJVazquez-Marouschek, CDopazo, JBorrego, SAntinolo, Ghttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1271MOLECULAR VISIONISSN: 10900535info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPurpose: Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by extreme genetic and clinical heterogeneity. Thus, the diagnosis is not always easily performed due to phenotypic and genetic overlap. Current clinical practices have focused on the systematic evaluation of a set of known genes for each phenotype, but this approach may fail in patients with inaccurate diagnosis or infrequent genetic cause. In the present study, we investigated the genetic cause of autosomal recessive RP (arRP) in a Spanish family in which the causal mutation has not yet been identified with primer extension technology and resequencing.
Methods: We designed a whole-exome sequencing (WES)-based approach using NimbleGen SeqCap EZ Exome V3 sample preparation kit and the SOLiD 5500x1 next-generation sequencing platform. We sequenced the exomes of both unaffected parents and two affected siblings. Exome analysis resulted in the identification of 43,204 variants in the index patient. All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. In silico prediction tools were used to determine mutational impact on protein function and the structure of the identified variants.
Results: Novel Usher syndrome type 2A (USH2A) compound heterozygous mutations, c.4325T>C (p. F1442S) and c.15188T>G (p.L5063R), located in exons 20 and 70, respectively, were identified as probable causative mutations for RP in this family. Family segregation of the variants showed the presence of both mutations in all affected members and in two siblings who were apparently asymptomatic at the time of family ascertainment. Clinical reassessment confirmed the diagnosis of RP in these patients.
Conclusions: Using WES, we identified two heterozygous novel mutations in USH2A as the most likely disease-causing variants in a Spanish family diagnosed with arRP in which the cause of the disease had not yet been identified with commonly used techniques. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases where conventional genetic approaches have previously failed in achieving a proper diagnosis.MOLECULAR VISIONenginfo:eu-repo/semantics/restrictedAccess2013-11-07oai:cipf.fundanetsuite.com:p12722026-04-06T13:29:27ZpubrevOptimised protocols for the metabolic profiling of S. cerevisiae by H-1-NMR and HRMAS spectroscopyPalomino-Schatzlein, MMolina-Navarro, MMTormos-Perez, MRodriguez-Navarro, SPineda-Lucena, Ahttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1272info:doi:10.1007/s00216-013-7271-9ANALYTICAL AND BIOANALYTICAL CHEMISTRYISSN: 16182642ISSNe: 16182650info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAn optimised extraction protocol for the analysis of Saccharomyces cerevisiae aqueous and organic metabolites by nuclear magnetic resonance spectroscopy that allows the identification and quantification of up to 50 different compounds is presented. The method was compared with other metabolic profiling protocols for S. cerevisiae, where generally different analytical techniques are applied for metabolite quantification. In addition, the analysis of intact S. cerevisiae cells by HRMAS was implemented for the first time as a complementary method. The optimised protocols were applied to study the metabolic effect of glucose and galactose on S. cerevisiae growth. Furthermore, the metabolic reaction of S. cerevisiae to osmotic stress has been studied.NMR; Yeast; HRMAS; Metabolomics; StressSPRINGER HEIDELBERGenginfo:eu-repo/semantics/restrictedAccess2013-10-01oai_dc////p1273