Phosphoproteome Analysis Reveals Estrogen-ER Pathway as a Modulator of mTOR Activity Via DEPTOR.

ER-positive breast tumors represent ∼70% of all breast cancer cases. Although their treatment with endocrine therapies is effective in the adjuvant or recurrent settings, the development of resistance compromises their effectiveness. The binding of estrogen to ERα, a transcription factor, triggers the regulation of the target genes (genomic pathway). Additionally, a cytoplasmic fraction of estrogen-bound ERα activates oncogenic signaling pathways such as PI3K/AKT/mTOR (nongenomic pathway). The upregulation of the estrogenic and the PI3K/AKT/mTOR signaling pathways are frequently associated with a poor outcome. To better characterize the connection between these two pathways, we performed a phosphoproteome analysis of ER-positive MCF7 breast cancer cells treated with estrogen or estrogen and the mTORC1 inhibitor rapamycin. Many proteins were identified as estrogen-regulated mTORC1 targets and among them, DEPTOR was selected for further characterization. DEPTOR binds to mTOR and inhibits the kinase activity of both mTOR complexes mTORC1 and mTORC2, but mitogen-activated mTOR promotes phosphorylation-mediated DEPTOR degradation. Although estrogen enhances the phosphorylation of DEPTOR by mTORC1, DEPTOR levels increase in estrogen-stimulated cells. We demonstrated that DEPTOR accumulation is the result of estrogen-ERα-mediated transcriptional upregulation of DEPTOR expression. Consequently, the elevated levels of DEPTOR partially counterbalance the estrogen-induced activation of mTORC1 and mTORC2. These results underscore the critical role of estrogen-ERα as a modulator of the PI3K/AKT/mTOR signaling pathway in ER-positive breast cancer cells. Additionally, these studies provide evidence supporting the use of dual PI3K/mTOR or dual mTORC1/2 inhibitors in combination with endocrine therapies as a first-line treatment option for the patients with ER-positive advanced breast cancer.

Estrogen receptor α promotes protein synthesis by fine-tuning the expression of the eukaryotic translation initiation factor 3 subunit f (eIF3f).

Approximately two thirds of all breast cancer cases are estrogen receptor (ER)-positive. The treatment of this breast cancer subtype with endocrine therapies is effective in the adjuvant and recurrent settings. However, their effectiveness is compromised by the emergence of intrinsic or acquired resistance. Thus, identification of new molecular targets can significantly contribute to the development of novel therapeutic strategies. In recent years, many studies have implicated aberrant levels of translation initiation factors in cancer etiology and provided evidence that identifies these factors as promising therapeutic targets. Accordingly, we observed reduced levels of the eIF3 subunit eIF3f in ER-positive breast cancer cells compared with ER-negative cells, and determined that low eIF3f levels are required for proper proliferation and survival of ER-positive MCF7 cells. The expression of eIF3f is tightly controlled by ERα at the transcriptional (genomic pathway) and translational (nongenomic pathway) level. Specifically, estrogen-bound ERα represses transcription of the EIF3F gene, while promoting eIF3f mRNA translation. To regulate translation, estrogen activates the mTORC1 pathway, which enhances the binding of eIF3 to the eIF4F complex and, consequently, the assembly of the 48S preinitiation complexes and protein synthesis. We observed preferential translation of mRNAs with highly structured 5'-UTRs that usually encode factors involved in cell proliferation and survival (e.g. cyclin D1 and survivin). Our results underscore the importance of estrogen-ERα-mediated control of eIF3f expression for the proliferation and survival of ER-positive breast cancer cells. These findings may provide rationale for the development of new therapies to treat ER-positive breast cancer.

Apoferritin Protein Amyloid Fibrils with Tunable Chirality and Polymorphism.

Ferritin, a soluble and highly robust protein with subunits packed into well-defined helices, is a key component of the iron regulatory system in the brain and thus is widely recognized as a crucial protein for iron metabolism, but may also bear possible implications in some neurodegenerative disorders. Here, we present evidence of how human recombinant apoferritin can convert into an unusual structure from its folded native state; that is, amyloid fibrils analogue to those found in pathological disorders such as Alzheimer's and Parkinson's diseases. An extensive combination of advanced microscopy, spectroscopy and scattering techniques concur to reveal that apoferritin fibrils possess a common double stranded twisted ribbon structure which can result in a mesoscopic right-handed chirality. We highlight a direct connection between the chirality and morphology of the resulting amyloid fibrils, and the initial protein subunits composition, advancing our understanding on the possible role of misfolding in some ferritin-related pathologies and posing new bases for the design of chiral 1D functional nanostructures.

A New Heterogeneous Catalyst Obtained via Supramolecular Decoration of Graphene with a Pd2+ Azamacrocyclic Complex.

A new G-(H2L)-Pd heterogeneous catalyst has been prepared via a self-assembly process consisting in the spontaneous adsorption, in water at room temperature, of a macrocyclic H2L ligand on graphene (G) (G + H2L = G-(H2L)), followed by decoration of the macrocycle with Pd2+ ions (G-(H2L) + Pd2+ = G-(H2L)-Pd) under the same mild conditions. This supramolecular approach is a sustainable (green) procedure that preserves the special characteristics of graphene and furnishes an efficient catalyst for the Cu-free Sonogashira cross coupling reaction between iodobenzene and phenylacetylene. Indeed, G-(H2L)-Pd shows an excellent conversion (90%) of reactants into diphenylacetylene under mild conditions (50 °C, water, aerobic atmosphere, 14 h). The catalyst proved to be reusable for at least four cycles, although decreasing yields down to 50% were observed.

Monitoring lactoferrin iron levels by fluorescence resonance energy transfer: a combined chemical and computational study.

Three forms of lactoferrin (Lf) that differed in their levels of iron loading (Lf, LfFe, and LfFe2) were simultaneously labeled with the fluorophores AF350 and AF430. All three resulting fluorescent lactoferrins exhibited fluorescence resonance energy transfer (FRET), but they all presented different FRET patterns. Whereas only partial FRET was observed for Lf and LfFe, practically complete FRET was seen for the holo form (LfFe2). For each form of metal-loaded lactoferrin, the AF350-AF430 distance varied depending on the protein conformation, which in turn depended on the level of iron loading. Thus, the FRET patterns of these lactoferrins were found to correlate with their iron loading levels. In order to gain greater insight into the number of fluorophores and the different FRET patterns observed (i.e., their iron levels), a computational analysis was performed. The results highlighted a number of lysines that have the greatest influence on the FRET profile. Moreover, despite the lack of an X-ray structure for any LfFe species, our study also showed that this species presents modified subdomain organization of the N-lobe, which narrows its iron-binding site. Complete domain rearrangement occurs during the LfFe to LfFe2 transition. Finally, as an example of the possible applications of the results of this study, we made use of the FRET fingerprints of these fluorescent lactoferrins to monitor the interaction of lactoferrin with a healthy bacterium, namely Bifidobacterium breve. This latter study demonstrated that lactoferrin supplies iron to this bacterium, and suggested that this process occurs with no protein internalization.

Gold nanoparticle-coated apoferritin conductive nanowires.

Gold-metallic nanofibrils were prepared from three different iso-apoferritin (APO) proteins with different Light/Heavy (L/H) subunit ratios (from 0% up to 100% L-subunits). We show that APO protein fibrils have the ability to in situ nucleate and grow gold nanoparticles (AuNPs) simultaneously assembled on opposite strands of the fibrils, forming hybrid inorganic-organic metallic nanowires. The AuNPs are arranged following the pitch of the helical APO protein fiber. The mean size of the AuNPs was similar in the three different APO protein fibrils studied in this work. The AuNPs retained their optical properties in these hybrid systems. Conductivity measurements showed ohmic behavior like that of a continuous metallic structure.

Magnetic nanoparticles--templated assembly of protein subunits: a new platform for carbohydrate-based MRI nanoprobes.

A new approach for the preparation of carbohydrate-coated magnetic nanoparticles is reported. In a first step, we show that the pH-driven assembly-disassembly natural process that occurs in apoferritin protein is effective for the encapsulation of maghemite nanoparticles of different sizes: 4 and 6 nm. In a second step, we demonstrate that the presence of functional amine groups in the outer shell of apoferritin allows functionalization with two carbohydrates, N-acetyl-D-glucosamine and d-mannose. High-resolution electron microscopy (HREM), high angle annular dark field scanning electron microscopy (HAADF-STEM), electron energy loss spectroscopy (EELS), X-ray diffraction (XRD), and SQUID technique have been used to characterize the magnetic samples, termed herein Apomaghemites. The in vivo magnetic resonance imaging (MRI) studies showed the efficiency in contrasting images for these samples; that is, the r(2) NMR relaxivities are comparable with Endorem (a commercial superparamagnetic MRI contrast agent). The r(2) relaxivity values as well as the pre-contrast and post-contrast T(2)*-weighted images suggested that our systems could be used as perspective superparamagnetic contrast agents for magnetic resonance imaging (MRI). The carbohydrate-functionalized Apomaghemite nanoparticles retained their recognition abilities, as demonstrated by the strong affinity with their corresponding carbohydrate-binding lectins.

Folliculin: A Regulator of Transcription Through AMPK and mTOR Signaling Pathways.

Folliculin (FLCN) is a tumor suppressor gene responsible for the inherited Birt-Hogg-Dubé (BHD) syndrome, which affects kidneys, skin and lungs. FLCN is a highly conserved protein that forms a complex with folliculin interacting proteins 1 and 2 (FNIP1/2). Although its sequence does not show homology to known functional domains, structural studies have determined a role of FLCN as a GTPase activating protein (GAP) for small GTPases such as Rag GTPases. FLCN GAP activity on the Rags is required for the recruitment of mTORC1 and the transcriptional factors TFEB and TFE3 on the lysosome, where mTORC1 phosphorylates and inactivates these factors. TFEB/TFE3 are master regulators of lysosomal biogenesis and function, and autophagy. By this mechanism, FLCN/FNIP complex participates in the control of metabolic processes. AMPK, a key regulator of catabolism, interacts with FLCN/FNIP complex. FLCN loss results in constitutive activation of AMPK, which suggests an additional mechanism by which FLCN/FNIP may control metabolism. AMPK regulates the expression and activity of the transcriptional cofactors PGC1α/ß, implicated in the control of mitochondrial biogenesis and oxidative metabolism. In this review, we summarize our current knowledge of the interplay between mTORC1, FLCN/FNIP, and AMPK and their implications in the control of cellular homeostasis through the transcriptional activity of TFEB/TFE3 and PGC1α/ß. Other pathways and cellular processes regulated by FLCN will be briefly discussed.

Binding and removal of sulfate, phosphate, arsenate, tetrachloromercurate, and chromate in aqueous solution by means of an activated carbon functionalized with a pyrimidine-based anion receptor (HL). Crystal structures of [H3L(HgCl4)]·H2O and [H3L(HgBr4)]·H2O showing anion-π interactions.

Binding of anions of great environmental concern such as SO(4)(2-), PO(4)(3-), AsO(4)(3-), HgCl(4)(2-), and CrO(4)(2-) by the protonated forms of a tren-like (tren = tris(2-aminoethyl)amine) ligand (HL) functionalized with a pyrimidine residue was studied by means of potentiometric measurements and isothermal titration calorimetry (ITC) affording log K, ΔH°, and TΔS° values for the formation of the relevant complexes. The complexes show high to very high stability due to the particular topology and electronic properties of the ligand which is able to use two separated coordination environments to host the anions, the protonated tren site where electrostatic and hydrogen bond interactions are operating, and the pyrimidine ring which may act via anion-π interaction. A contribution of -8.9 ± 0.4 kJ/mol for pyrimidine-anion interaction in water was derived for SO(4)(2-) binding. The crystal structures of [H(3)L(HgCl(4))]·H(2)O (1), [H(3)L(HgBr(4))]·H(2)O (2), and that previously reported for [H(3)L(CdI(4))], clearly show these binding features in the solid state. A hybrid AC-HL material obtained by adsorption of HL on commercial activated carbon (AC) was used to study the removal of these anions from water. AC-HL shows enhanced adsorption capacity toward all the anions studied with respect to AC. This behavior is ascribed to the stronger interaction of anions with the HL function of AC-HL than with the Cπ-H(3)O(+) sites of the unfunctionalized AC.

Impacto del momento de medición y de la sintomatología acontecida durante la hemodiálisis en la Calidad de Vida percibida por el paciente / Impact of measurement timing and symptomatology during hemodialysis on perceived quality of life by the patient

Objetivo: Determinar la relación entre calidad de vida percibida por el paciente en hemodiálisis, el momento de medición de esta y el número de síntomas/complicaciones acontecidos durante la sesión.Material y Método: Estudio observacional longitudinal en pacientes en hemodiálisis con capacidad cognitiva conservada. Se recogieron variables sociodemográficas y clínicas, así como calidad de vida mediante instrumento Coop-Wonka.El estudio se desarrolló en 2 fases:Primera fase: evaluación calidad de vida preHD, cuestionario autoadministrado (en las 12 h previas a 1ª sesión semanal).Segunda fase: 4 semanas más tarde, cumplimentación del mismo cuestionario de calidad de vida, administrado por enfermería (al finalizar 1ª sesión semanal).Durante cuatro semanas se recogieron todos los síntomas, complicaciones mecánicas y situaciones de estrés experimentadas por el paciente durante las sesiones.Resultados: Se estudiaron 61 pacientes, 39 hombres (64%). Edad 67,7±13 años. Tiempo en hemodiálisis 68,7±79 meses. Las puntuaciones globales de calidad de vida relacionada con la salud fueron 25,6±6,9 puntos (1ª fase) y 24,2±7 puntos (2ª fase), con diferencias significativas entre ambos periodos. Se registraron 328 síntomas (0,44±0,54/paciente y sesión).El tiempo en hemodiálisis se relacionó con sintomatología y calidad de vida, presesión y post-sesión.Y la sintomatología se relacionó con calidad de vida relacionada con la salud pre y post-sesión.Conclusiones: A mayor tiempo en hemodiálisis los pacientes presentan peor calidad de vida y más sintomatología durante las sesiones. La percepción sobre su estado de salud, es mejor post-sesión en comparación con la percibida antes de la sesión de diálisis. (AU)

Objective: To determine the relationship between patients’ perceived quality of life on hemodialysis, the timing of its measurement, and the number of symptoms/complications occurring during the session.Material and Method: Longitudinal observational study in hemodialysis patients with preserved cognitive capacity. Sociodemographic and clinical variables and quality of life were collected using the Coop-Wonka instrument. The study was conducted in 2 phases:First phase: pre-HD quality of life evaluation, self-administered questionnaire (12 hours before the 1st weekly session).Second phase: 4 weeks later, completion of the same quality of life questionnaire, administered by nursing staff at the end of the 1st weekly session. All symptoms, mechanical complications, and stress situations experienced by the patient during the sessions were recorded for four weeks.Results: Sixty-one patients were studied, 39 men (64%). The mean age was 67.7±13 years. Time on hemodialysis was 68.7±79 months. Overall scores for health-related quality of life were 25.6±6.9 points (1st phase) and 24.2±7 points (2nd phase), with significant differences between both periods. 328 symptoms were recorded (0.44±0.54/patient and session). Time on hemodialysis was related to symptomatology and quality of life, pre-session and post-session. Symptoma-tology was related to health-related quality of life pre and post-session.Conclusions: Patients who have been on hemodialysis for more extended periods have worse quality of life and more symptoms during the sessions. Their perception of their health status is better post-session compared to pre-dialysis sessions. (AU)

Comparative structural and chemical studies of ferritin cores with gradual removal of their iron contents.

Transmission Electron Microscopy (TEM), X-ray Absorption Near Edge Spectroscopy (XANES), Electron Energy-Loss Spectroscopy (EELS), Small-Angle X-ray Scattering (SAXS), and SQUID magnetic studies were performed in a batch of horse spleen ferritins from which iron had been gradually removed, yielding samples containing 2200, 1200, 500, and 200 iron atoms. Taken together, findings obtained demonstrate that the ferritin iron core consists of a polyphasic structure (ferrihydrite, magnetite, hematite) and that the proportion of phases is modified by iron removal. Thus, the relative amount of magnetite in ferritin containing 2200 to 200 iron atoms rose steadily from approximately 20% to approximately 70% whereas the percentage of ferrihydrite fell from approximately 60% to approximately 20%. These results indicate a ferrihydrite-magnetite core-shell structure. It was also found that the magnetite in the ferritin iron core is not a source of free toxic ferrous iron, as previously believed. Therefore, the presence of magnetite in the ferritin cores of patients with Alzheimer's disease is not a cause of their increased brain iron(II) concentration.

Varying iron release from transferrin and lactoferrin proteins. A laboratory experiment.

Iron metabolism is an important subject of study for undergraduate students of chemistry and biochemistry. Relevant laboratory exercises are scarce in the literature but would be very helpful in assisting students grasp key concepts. The experiment described here deals with different iron release mechanisms of two protagonists in iron metabolism: serum transferrin (Tf) and lactoferrin (Lf). Despite having very similar structures and iron-binding sites, Tf releases practically all its iron at pH 5.5 while Lf requires a significantly lower pH of 3. This difference in behavior is directly related to their respective biological functions as Tf blood-borne iron into the cell, while Lf competes with pathogens to sequester iron in biological fluids at more acidic pHs. During this experiment, the students will carry out iron loading and unloading on both human Lf and Tf and monitor the iron release at different pHs using UV-Vis spectroscopy. With this simple approach, the students will discover the different patterns of iron release of Tf and Lf and how this variance in behavior relates to their biological functions. Furthermore, this laboratory practice can be expanded to allow students to investigate a variety of iron proteins. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):521-527, 2017.

RSK-mediated down-regulation of PDCD4 is required for proliferation, survival, and migration in a model of triple-negative breast cancer.

The p90 ribosomal S6 kinase (RSK) is a family of MAPK-activated serine/threonine kinases (RSK1-4) whose expression and/or activity are deregulated in several cancers, including breast cancer. Up-regulation of RSKs promotes cellular processes that drive tumorigenesis in Triple Negative Breast Cancer (TNBC) cells. Although RSKs regulate protein synthesis in certain cell types, the role of RSK-mediated translational control in oncogenic progression has yet to be evaluated. We demonstrate that proliferation and migration of TNBC MDA-MB-231 cells, unlike ER/PR-positive MCF7 cells, rely on RSK activity. We show that RSKs regulate the activities of the translation initiation factor eIF4B and the translational repressor PDCD4 in TNBC cells with up-regulated MAPK pathway, but not in breast cancer cells with hyperactivated PI3K/Akt/mTORC1 pathway. These results identify PDCD4 as a novel RSK substrate. We demonstrate that RSK-mediated phosphorylation of PDCD4 at S76 promotes PDCD4 degradation. Low PDCD4 levels reduce PDCD4 inhibitory effect on the translation initiation factor eIF4A, which increases translation of "eIF4A sensitive" mRNAs encoding factors involved in cell cycle progression, survival, and migration. Consequently, low levels of PDCD4 favor proliferation and migration of MDA-MB-231 cells. These results support the therapeutic use of RSK inhibitors for treatment of TNBC with deregulated MAPK/RSK pathway.

Apoferritin fibers: a new template for 1D fluorescent hybrid nanostructures.

Recently, research in the field of protein amyloid fibers has gained great attention due to the use of these materials as nanoscale templates for the construction of functional hybrid materials. The formation of apoferritin amyloid-like protein fibers is demonstrated herein for the first time. The morphology, size and stiffness of these one-dimensional structures are comparable to the fibers formed by ß-lactoglobulin, a protein frequently used as a model in the study of amyloid-like fibrillar proteins. Nanometer-sized globular apoferritin is capable of self-assembling to form 1D micrometer-sized structures after being subjected to a heating process. Depending on the experimental conditions, fibers with different morphologies and sizes are obtained. The wire-like protein structure is rich in functional groups and allows chemical functionalization with diverse quantum dots (QD), as well as with different Alexa Fluor (AF) dyes, leading to hybrid fluorescent fibers with variable emission wavelengths, from green to near infrared, depending on the QD and AFs coupled. For fibers containing the pair AF488 and AF647, efficient fluorescence energy transfer from the covalently coupled donor (AF488) to acceptor tags (AF647) takes place. Apoferritin fibers are proposed here as a new promising template for obtaining hybrid functional materials.

Metal-Purine Interactions: Homo- and Heterodinuclear Platinum(II) and/or Palladium(II) Complexes of 8-Thiotheophylline. Crystal Structures of [Pt(&mgr;-TT)(dppm)](2).2DMSO and [(dppm)Pt(&mgr;-TT)(2)Pd(dppm)].7H(2)O.

The reaction of cis-[MCl(2)(dppm)] (M = Pt(II) and Pd(II); dppm = bis(diphenylphosphino)methane) with H(2)TT and NaOH (H(2)TT = 8-thiotheophylline) yields neutral mononuclear [M(HTT-S(8))(2)(dppm)] complexes. Homodinuclear [M(&mgr;-TT-N(7),S(8))(dppm)](2) (M = Pt(II) and Pd(II)) are prepared either by the reaction of [M(HTT)(2)(dppm)] with cis-[MCl(2)(dppm)] and NaOH or by the direct reaction of cis-[MCl(2)(dppm)] with Na(2)TT, prepared in situ from H(2)TT and NaOH. The crystal structure of the Pt derivative is reported: [Pt(&mgr;-TT)(dppm)](2).2DMSO (3) crystallizes in the triclinic space group P&onemacr; with a = 12.949(3) Å, b = 13.009(3) Å, c = 22.980(5) Å, alpha = 96.89(3) degrees, beta = 103.53(3) degrees, gamma = 106.43(3) degrees, Z = 2, and R(1) = 0.045. Heterodinuclear [(dppm)Pt(&mgr;-TT)(2)Pd(L-L)] complexes are obtained by reaction of [Pt(HTT)(2)(dppm)] with [PdCl(2)(L-L)] in basic medium (L-L = dppm and 2,2'-bipyridine). The crystal structure of [(dppm)Pt(&mgr;-TT)(2)Pd(dppm)].7H(2)O (5) is reported. The complex crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 16.560(5) Å, b = 17.063(5) Å, c = 24.428(5) Å, Z = 4, and R(1) = 0.042. The structures of 3 and 5 are almost identical, by which 5 can be seen as an isomorphic substitution of one of the Pt(II) ions of 3 by a Pd(II) ion. The structures consist of dinuclear units having a pseudo-2-fold axis perpendicular to that defined by the metal atoms. The two metal atoms are bibridged by two &mgr;-TT-N(7),S(8) ligands, in a head to tail arrangement. The square-planar coordination of the metal atoms is completed by a chelate dppm ligand. The steric repulsions between the bulky dppm ligands must be the main factor precluding metal-metal interaction in these compounds.

Gold(I)-Purine Interactions: Synthesis and Characterization of Cyclic and Open Chain Polynuclear Gold(I) Complexes Containing Xanthine Derivatives and Bis(phosphine) as Bridging Ligands. Crystal Structures of [Au(2)(&mgr;-HX)(&mgr;-dmpe)].3H(2)O and [Au(2)(&mgr;-TT)(&mgr;-dmpe)].H(2)O (H(3)X = Xanthine; H(2)TT = 8-Mercaptotheophylline).

The reaction of [(AuBr)(2)(&mgr;-PR(2)P(CH(2))(n)()PR(2))] (where R = CH(3) for n = 1; R = Ph for n = 1, 3, 4) with N-alkylxanthine and thioxanthine derivatives, containing two ionizable protons in close positions, yields, under basic conditions, neutral heterobridged dinuclear gold(I) ring complexes [Au(&mgr;-L)(2)(&mgr;-PR(2)P(CH(2))(n)()PR(2))], which have been investigated by means of (1)H- and (31)P-NMR and FAB spectroscopies. Crystal structures of two of these complexes are reported. [Au(2)(&mgr;-HX)(&mgr;-dmpe)].3H(2)O (1) (H(3)X = xanthine; dmpe = 1,2-bis(dimethylphosphine)ethane) crystallizes in the monoclinic space group P2(1)/n with a = 9.348(2) Å, b = 8.656(2) Å, c = 24.585(5) Å, beta = 98.24(2) degrees, Z = 4, and R = 0.040. [Au(2)(&mgr;-TT)(&mgr;-dmpe)].H(2)O (2) crystallizes in the monoclinic space group P2(1)/n with a = 10.853(4) Å, b = 14.031(6) Å, c = 13.574(5) Å, beta = 100.80(4) degrees, Z = 4, and R = 0.063. The structures of 1 and 2 are similar and consist of dinuclear nine-membered ring molecules, in which the two linear two-coordinate gold atoms are bridged on one side by a dmpe ligand and on the other side by a bidentate xanthinato dianion, with intramolecular Au.Au distances of 3.053(1) and 2.952 (2) Å, respectively. In the former, the coordination of the xanthinato ligand to the gold atoms takes place through the N3 and N9 nitrogen atoms whereas, in the latter, N7,S8-chelate coordination of the 8-thiotheophyllinato dianion occurs. The magnitude of the Au.Au separation is analyzed in terms of the twisting of the xanthine derivative ligand from the plane containing the gold(I) and phosphorus atoms. For n = 6 the steric requirements of the Au(&mgr;-dpph)Au group prevents the formation of dinuclear ring complexes and open chain complexes are obtained. Finally, when the xanthine derivatives do not contain two close active coordination sites dinuclear open chain complexes are formed.

[Au(2)(micro-G)(micro-dmpe)].(KBr)(0.75) 2H(2)O, a cyclic dinuclear gold(I) complex with an N3,N9-bridging coordination mode of guanine and aurophilic interactions: synthesis, X-ray crystal structure and luminescence properties (dmpe=1,2-bis(dimethylphosphino)ethane and G=guaninato dianion).

The digold complex [Au(2)(micro-G)(micro-dmpe)](KBr)(0.75) x 2H(2)O (dmpe=1,2-bis(dimethylphosphino)ethane (1)) has been prepared by nucleophilic attack of the guaninate dianion on the gold(I) atoms of [(AuBr)(2)(micro-dmpe)] and has been characterised by X-ray crystallography and spectroscopic studies. The structure of 1 consists of dinuclear nine-membered ring molecules, K(+) cations, Br(-) anions and water molecules, all of them involved in either weak K....O or hydrogen bonding interactions. Within the cyclic dinuclear molecules, gold(I) atoms are bridged on one side by the diphosphine ligand and on the other side by a doubly deprotonated guaninate anion coordinated through neighbouring N3 and N9 nitrogen atoms, with gold(I)....gold(I) interactions of 3.030(2) A. This is the first X-ray example showing an N3,N9-bridging mode for guanine. There are two types of K(+) cations in the structure, K1 and K2. The former interacts with water molecules to form a unique [K(H(2)O)(3)(micro-H(2)O)(2)K(H(2)O)(3)](2+) dipotassium unit whereas K2 interact with the O6 atom of the guaninate ligands and oxygen atoms of the dipotassium unit leading to a chain running along the c-axis. Each chain is interdigitated with four neighbouring ones to give rise to an intricate network in which Br1, Br2 and [K(H(2)O)(3)(micro-H(2)O)(2)K(H(2)O)(3)](2+) fit snugly into cavities defined by digold molecules. Complex 1 luminescence at room temperature and 77 K in the solid state with excitation maxima at 385 nm and emission maxima at 451.8 and 448.7 nm, respectively. The emission spectrum of a saturated solution of 1 in DMSO (dimethyl sulfoxide) shows the maximum at about 440 nm.

Análisis del impacto de la producción científica de la revista Enfermería Nefrológica entre 1998 y 2017 / Analysis of the impact of the scientific production of the journal Enfermería Nefrológica between 1998 and 2017

Introducción: Enfermería Nefrológica es la publicación oficial de la Sociedad Española de Enfermería Nefrológica, que cumple su 20 aniversario. El análisis de los artículos de una revista permite determinar la evolución de una publicación. Objetivo: Analizar la producción científica publicada en la revista Enfermería Nefrológica durante el periodo 1998-2017. Material y Método: Estudio bibliométrico descriptivo transversal de la revista Enfermería Nefrológica, del volumen 1 al 20, mediante el software "Publish or Perish" V6. Se analizaron las siguientes variables: número total de artículos y de citas; citas por artículo, por autor, por año; artículos por autor y autores por artículo; AWCR, índice g e índice h. Se realizaron análisis por periodos de 5 años (Periodo-1 1998-2002, Periodo-2 2003-2007, Periodo-3 2008-2011, Periodo-4 2012-2017). Resultados: Se analizaron 1198 artículos: Periodo-1 n=81 (6,76%), Periodo-2 n=160 (13,35%), Periodo-3 n=164 (13,68%), Periodo-4 n=793 (66,19%); y 2167 citaciones: Periodo-1 n=47 (2,17%), Periodo-2 n=759 (35%), Periodo-3 n=782 (36%), Periodo-4 n=579 (26,7%). Media de autores por artículo: Periodo-1: 1,96, Periodo-2: 2,66, Periodo-3: 2,82, Periodo-4: 3. AWCR: Periodo-1: 2,80 (sqrt=1,67) 1,58/autor, Periodo-2: 60,33 (sqrt=7,77) 26,58/autor, Periodo-3: 93,93 (sqrt=9,69), 35,21/autor, Periodo-4: 147,12 (sqrt=12,13), 57,31/autor. Índice h: Periodo-1: 4 (a=2,94, m=0,20, 35 citas=74,5% cobertura), Periodo-2: 16 (a=2,96, m=1,07, 433 citas=57,0% cobertura), Periodo-3: 9 (a=7,15, m=1,50, 116 citas=20,0% cobertura), Periodo-4: 11 (g/h=1,22, 133 citas=23,0% cobertura). Conclusiones: La revista Enfermería Nefrológica ha crecido de forma exponencial en los últimos 20 años, tanto en volumen de producción como en calidad y visibilidad, convirtiéndose en la publicación de referencia del cuidado renal en el ámbito hispano-hablante

Introduction: The Journal Enfermería Nefrológica (EN) is the official publication of the Spanish Nephrology Nursing Association (SEDEN), and in 2018, EN celebrates its 20th anniversary. Analysis of journal articles allows to determine the publication's evolution. Aim: To analyze the scientific production published in the journal EN during the period 1998-2017. Material and Method: Bibliometric cross-sectional descriptive study of the journal EN from volume 1 to 20, using the software "Publish or Perish" 6th version. The following variables were analyzed: total number of articles and citations; citations per article, per author, per year; articles by author and authors by article; AWCR, g-index and h-index. Five-year periods analyzes were carried out (Period-1 1998-2002, Period-2 2003-2007, Period-3 2008-2011, Period-4 2012-2017). Results: 1198 articles were analyzed: Period-1 n=81 (6.76%), Period-2 n=160 (13.35%), Period-3 n=164 (13.68%), Period-4 n=793 (66.19%); and 2167 citations: Period-1 n=47 (2.17%), Period-2 n= 759 (35%), Period-3 n=782 (36%), Period-4 n=579 (26.7%). Average number of authors per article: Period-1 1.96, Period-2 2.66, Period-3 2.82, Period-4 3. AWCR: Period-1 2.80 (sqrt=1.67) 1.58/author, Period-2 60.33 (sqrt=7.77) 26.58/author, Period-3 93.93 (sqrt=9.69), 35.21/author, Period-4 147.12 (sqrt=12.13), 57.31/author. H index: Period-1 4 (a=2.94, m=0.20, 35 cites=74.5% coverage), Period-2 16 (a=2.96, m=1.07, 433 cites=57.0% coverage), Period-3 9 (a=7.15, m=1.50, 116 cites=20.0% coverage), Period-4 11 (g/h=1.22, 133 cites=23.0% coverage). Conclusions: The journal EN has grown exponentially in the last 20 years, both in production volume and in quality and visibility, becoming the reference publication of renal care in the Spanish-speaking world

A new approach to the ferritin iron core growth: influence of the H/L ratio on the core shape.

An electron microscopy study, in combination with modeling and image simulation, of four different reconstituted ferritin samples: recombinant human H and L homopolymers, and H and L heteropolymers of native L-subunit-rich horse spleen and H-subunit-rich human heart ferritins, points out the existence of a correlation between iron core shape and protein shell.

Análisis de la punción de prótesis intravasculares recubiertas tras el rescate de la fístula arteriovenosa después de 12 meses de experiencia / Analysis of puncture of coated intravascular prostheses after salvage of arteriovenous fistula, after 12 months of experience

Objetivos: Evaluar la eficacia a medio plazo de una nueva prótesis intravascular (VIABAHN(R)), y su seguridad, analizando la incidencia de eventos adversos asociados a su punción. Pacientes y Método: Se estudiaron 20 pacientes, a los que se les implantó VIABAHN(R), por pseudoaneurismas con trombosis, úlceras en las zonas de punción, fracaso de angioplastia o reestenosis en menos de 6 meses. Se estudió: Parámetros de la FAV, permeabilidad primaria y secundaria (6 y 12 meses), presencia de complicaciones y control del deterioro de la prótesis mediante flebografía a los 3 y 6 meses. Para la punción se esperó un periodo de 4 semanas. Resultados: Se analizó un periodo de 15±9.4 meses. La media de los parámetros funcionales de la FAV durante la hemodiálisis fue: Fs: 362.5±43.3 ml/min, PA: -209.5±35.6 mmHg, PV: 215.8±34.5 mmHg, Kt 55±5.4 l y Recirculación 12.7±3.7%. A los 6 meses el 66% (IC 95% 54-77) de los pacientes tenía permeabilidad primaria y el 77% (IC 95% 67-87) tenía permeabilidad secundaria. A los 12 meses el 38% (IC 95% 24-52) permeabilidad primaria y el 76% (IC 95% 66-87) permeabilidad secundaria. No se observaron eventos adversos relacionados con la punción, ni se objetivó radiológicamente deterioro en las prótesis. Hubo un episodio de infección que requirió la retirada de la prótesis. Conclusiones: La prótesis vascular recubierta VIABAHN(R) es eficaz y segura en el rescate de las FAVs nativas estenosadas y/o trombosadas, ya que proporciona excelentes parámetros de diálisis y alta permeabilidad primaria y secundaria, sin que su punción repetida se asocie a complicaciones (AU)

Aim: To evaluate the medium-term efficacy of a new intravascular prosthesis (VIABAHN(R)), and its safety, by analyzing the incidence of adverse events associated with its puncture. Patients and method: Twenty patients, with VIABAHN(R) implanted, were studied for pseudoaneurysms with thrombosis, ulcers in the puncture sites, failure of angioplasty or restenosis in less than 6 months. Parameters of AVF, primary and secondary patency (6 and 12 months), presence of complications and control of prosthesis deterioration by phlebography at 3 and 6 months were studied. For the puncture, a period of 4 weeks was expected. Results: A period of 15 ± 9.4 months was analyzed. The mean of the functional parameters of the AVF during hemodialysis was: blood flow rate: 362.5 ± 43.3 ml / min, Arterial Pressure: -209.5 ± 35.6 mmHg, Venous Pressure: 215.8 ± 34.5 mmHg, Kt 55 ± 5.4 l and recirculation 12.7 ± 3.7%. At 6 months, 66% (95% CI: 54-77) of the patients had primary permeability and 77% (95% CI 67-87) had secondary permeability. At 12 months 38% (IC 95% 24-52) primary permeability and 76% (IC 95% 66-87) secondary permeability. No adverse events related to the puncture, nor radiologically objectified deterioration in prostheses were observed. There was an episode of infection requiring removal of the prosthesis. Conclusión: The VIABAHN(R) coated vascular prosthesis is effective and safe in the rescue of stented and / or thrombosed native AVFs, as it provides excellent dialysis parameters and high primary and secondary permeability, without repeated puncture associated with complications (AU)