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Cristina Riggio,1,* Maria Pilar Calatayud,2,* Clare Hoskins,3 Josephine Pinkernelle,4 Beatriz Sanz,2 Teobaldo Enrique Torres,2,5 Manuel Ricardo Ibarra,2,5 Lijun Wang,3 Gerburg Keilhoff,4 Gerardo Fabian Goya,2,5 Vittoria Raffa,1,6 Alfred Cuschieri1,3 1Institute of Life Science, Scuola Superiore Sant’Anna, Piazza Martiri della Libertà, Pisa, Italy; 2Instituto de Nanociencia de Aragón, Universidad de Zaragoza. Mariano Esquillor, Zaragoza, Spain; 3IMSaT, Institute for Medical Science and Technology, University of Dundee, Dundee, Scotland; 4Otto-von-Guericke University, Institute of Biochemistry and Cell Biology, Magdeburg, Germany; 5Departamento de Física de la Materia Condensada, Facultad de Ciencias, Universidad de Zaragoza. Cerbuna 12, Zaragoza, Spain; 6Department of Biology, Università di Pisa, Pisa, Italy*These authors contributed equally to this workPurpose: It has been proposed in the literature that Fe3O4 magnetic nanoparticles (MNPs) could be exploited to enhance or accelerate nerve regeneration and to provide guidance for regenerating axons. MNPs could create mechanical tension that stimulates the growth and elongation of axons. Particles suitable for this purpose should possess (1) high saturation magnetization, (2) a negligible cytotoxic profile, and (3) a high capacity to magnetize mammalian cells. Unfortunately, the materials currently available on the market do not satisfy these criteria; therefore, this work attempts to overcome these deficiencies.Methods: Magnetite particles were synthesized by an oxidative hydrolysis method and characterized based on their external morphology and size distribution (high-resolution transmission electron microscopy [HR-TEM]) as well as their colloidal (Z potential) and magnetic properties (Superconducting QUantum Interference Devices [SQUID]). Cell viability was assessed via Trypan blue dye exclusion assay, cell doubling time, and MTT cell proliferation assay and reactive oxygen species production. Particle uptake was monitored via Prussian blue staining, intracellular iron content quantification via a ferrozine-based assay, and direct visualization by dual-beam (focused ion beam/scanning electron microscopy [FIB/SEM]) analysis. Experiments were performed on human neuroblastoma SH-SY5Y cell line and primary Schwann cell cultures of the peripheral nervous system.Results: This paper reports on the synthesis and characterization of polymer-coated magnetic Fe3O4 nanoparticles with an average diameter of 73 ± 6 nm that are designed as magnetic actuators for neural guidance. The cells were able to incorporate quantities of iron up to 2 pg/cell. The intracellular distribution of MNPs obtained by optical and electronic microscopy showed large structures of MNPs crossing the cell membrane into the cytoplasm, thus rendering them suitable for magnetic manipulation by external magnetic fields. Specifically, migration experiments under external magnetic fields confirmed that these MNPs can effectively actuate the cells, thus inducing measurable migration towards predefined directions more effectively than commercial nanoparticles (fluidMAG-ARA supplied by Chemicell). There were no observable toxic effects from MNPs on cell viability for working concentrations of 10 µg/mL (EC25 of 20.8 µg/mL, compared to 12 µg/mL in fluidMAG-ARA). Cell proliferation assays performed with primary cell cultures of the peripheral nervous system confirmed moderate cytotoxicity (EC25 of 10.35 µg/mL).Conclusion: These results indicate that loading neural cells with the proposed MNPs is likely to be an effective strategy for promoting non-invasive neural regeneration through cell magnetic actuation.Keywords: magnetic nanoparticle, actuator, migration, neural regeneration

The combination of magnetoresistive sensors and magnetic labeling of bioanalytes, which are selectively captured by their complementary antibody in the proximity of the sensor is a powerful method in order to attain truly quantitative immunological assays. In this paper we present a technical solution to exploit the existing spin valve technology to readout magnetic signals of bio-functionalized magnetic nanoparticles. The method is simple and reliable, and it is based on a discrete scan of lateral flow strips with a precise control of the contact force between sensor and sample. It is shown that the signal of the sensor is proportional to the local magnetization produced by the nanoparticles in a wide range of concentrations, and the sensitivity thresholds in both calibration samples and real immunorecognition assays of human chorionic gonadotropin hormone are well below the visual inspection limit (5.5. ng/ml). Furthermore the sample scanning approach and the reduced dimensions of the sensors provide unprecedented spatial resolution of the nanoparticle distribution across the supporting nitrocellulose strip, therefore enabling on-stick control references and multi-analyte capability. © 2012 Elsevier B.V., Financial support by the Spanish Ministry of Science (through projects NAN2004-09270-CO3-03, PROFIT CIT 010000-2007-27, CONSOLIDER NANOBIOMED, and INNPACTO subprogram grant no. IPT-010000-2010-2) and by the EU (through SUDOE-Train2) is acknowledged.

To investigate the effects of alternating magnetic fields (AMF) on the death rate of dendritic cells (DCs) loaded with magnetic nanoparticles (MNPs) as heating agents. AMF exposure time and amplitude as well as the MNPs concentration were screened to assess the best conditions for a controlled field-induced cell death.Human-monocyte-derived DCs were co-incubated with dextran-coated MNPs. The cells were exposed to AMF (f = 260 kHz; 0H(0)12.7 kA/m) for intervals from 5 to 15 min. Morphology changes were assessed by scanning electron microscopy. Cell viability was measured by Trypan blue and fluorescence-activated cell sorting (FACS) using Annexin-propidium iodide markers.We were able to control the DCs viability by a proper choice AMF amplitude and exposure time, depending on the amount of MNPs uploaded. About 20% of cells showed Annexin-negative/PI-positive staining after 5-10 min of AMF exposure.Controlled cell death of MNP-loaded DCs can be obtained by adequate tuning of the physical AMF parameters and MNPs concentration. Necrotic-like populations were observed after exposure times as short as 10 min, suggesting a fast underlying mechanism for cell death. Power absorption by the MNPs might locally disrupt endosomic membranes, thus provoking irreversible cell damage.

The bacterium Pseudomonas syringae pv. syringae (Pss) is a pathogen of many plant species and causes, for example, brown spot disease in bean plants (Phaseolus vulgaris). Pss excretes the syringolins, natural product molecules that act as a virulence factors and inhibit the proteasome of the host plants.Proteasome inhibitors belong to an important class of anticancer agents and bortezomib (Velcade(®)) has been Food and Drug Administration-approved for the treatment of multiple myeloma (MM) and mantle cell lymphoma. Syringolins represent a new class of proteasome inhibitors and the present work was undertaken to design a potent syringolin-inspired analogue (TIR-203) for anticancer drug development.TIR-203 was tested against human MM and neuroblastoma (NB) cells. Cancer cells were treated with TIR-203 at various concentrations (0-10 µM) and the cell viability was measured using the MTS assay. To determine the effects on proteasomal activities, the cell culture-based proteasome inhibition assay was used. Syringolin A (SylA) and bortezomib were included as controls.TIR-203 inhibited the cell proliferation of MM and NB cells in a dose-dependent manner at significantly lower concentrations than SylA. In MM cells, TIR-203 effectively inhibited the chymotrypsin-like (CT-L), caspase-like (C-L), and trypsin-like (T-L) activities of the proteasome. In NB cells, TIR-203 inhibited the CT-L and C-L activities, but not the T-L activity.The newly designed proteasome inhibitor TIR-203 is more potent than the natural product SylA and strongly inhibits the cell viability and proteasomal activity of MM and NB cells.

The concise and modular total synthesis of the bacterial natural product and irreversible proteasome inhibitor syringolin B has been achieved. This synthesis has enabled the ready preparation of three diverse, structurally modified syringolin derivatives. The actions of these compounds in inhibiting the proliferation of neuroblastoma cell lines was evaluated, and significant enhancements in potency compared to the natural product were realized.

9 páginas, 4 figuras, 1 tabla.-- This is an Open Access article under the terms of the Creative Commons Attribution License., The most outstanding feature of scanning force microscopy (SFM) is its capability to detect various different short and long range interactions. In particular, magnetic force microscopy (MFM) is used to characterize the domain configuration in ferromagnetic materials such as thin films grown by physical techniques or ferromagnetic nanostructures. It is a usual procedure to separate the topography and the magnetic signal by scanning at a lift distance of 25–50 nm such that the long range tip–sample interactions dominate. Nowadays, MFM is becoming a valuable technique to detect weak magnetic fields arising from low dimensional complex systems such as organic nanomagnets, superparamagnetic nanoparticles, carbon-based materials, etc. In all these cases, the magnetic nanocomponents and the substrate supporting them present quite different electronic behavior, i.e., they exhibit large surface potential differences causing heterogeneous electrostatic interaction between the tip and the sample that could be interpreted as a magnetic interaction. To distinguish clearly the origin of the tip–sample forces we propose to use a combination of Kelvin probe force microscopy (KPFM) and MFM. The KPFM technique allows us to compensate in real time the electrostatic forces between the tip and the sample by minimizing the electrostatic contribution to the frequency shift signal. This is a great challenge in samples with low magnetic moment. In this work we studied an array of Co nanostructures that exhibit high electrostatic interaction with the MFM tip. Thanks to the use of the KPFM/MFM system we were able to separate the electric and magnetic interactions between the tip and the sample., The authors acknowledge the financial support from the Spanish Ministerio Ciencia e Innovación through the projects CSD2010-00024, MAT2007-65420-C02-01, MAT2008-06567- C02 (including FEDER funding) and CAM grant S2009/MAT- 1467. M. J. gives thanks for the JdC contract.

The proteasome has been recognized as a druggable target in cancer cells, and this has led to searches for pharmacologic agents that target this cellular organelle for cancer therapeutic purposes. Syrbactins are a group of microbial metabolites consisting of two related families, the glidobactins and the syringolins. Some members of this group have revealed cytotoxic efficacy in tumor cells, and more recently it was discovered that they exert proteasome-inhibitory function. Based on this therapeutic promise and to gain further understanding of their molecular modes of action, we chemically synthesized de-novo three novel syrbactin analogs and characterized their proteasome-inhibitory and in vitro anti-neoplastic activity in human cell lines representing multiple myeloma, Waldenström's macroglobulinemia, and lymphocytic leukemia. Our results show that two of these novel compounds are able to inhibit proteasome activity in the nanomolar range, reduce the expression of anti-apoptotic proteins survivin and Mcl-1, and cause severe endoplasmic reticulum (ER) stress, resulting in pronounced tumor cell death. These anticancer effects can be synergistically enhanced when the agents are combined with thapsigargin, which further aggravates ER stress by a different mechanism. Taken together, our findings support the notion that syrbactin analogs may provide a structural platform for the development of novel cancer therapeutics, and that their efficacy may be further increased when complemented with other agents that trigger ER stress.

Native starch (corn, potato and waxy corn) and phosphorylated corn starch blended with bagasse fiber and glycerol were used for the preparation of biodegradable films. The processing extrusion variables were: feed moisture FM (18.25–20.5%), fiber content FC (0–10%) and type of starch TS (native or phosphorylated). The analysis of infrared spectroscopy showed OH and C–O bands at 2750–3250 and 550–1000 cm−1, related to plasticizer–starch interactions. Films processed without fiber revealed peaks of low intensity associated to the plastizicing of starch. Differential scanning calorimeter displayed some changes in calorific capacity that could be attributed to molecular excitations and the mobility of polymeric chains (Tg) in a range of temperature between 40 and 80 °C. The dynamic mechanical analyses presented a decrease in the loss modulus at a temperature lower than 100 °C associated to a more structural mobility of bonds indicating a film with more flexibility. The thermal and microstructural characterization of films showed appropriate functional properties in the development of packing materials or flexible containers type bag.

A detailed study of Strontium substitution (up to 25% at most) with Lanthanide (La, Nd and Sm) in the Sr2CrReO6 double perovskite has been carried out by means of neutron powder diffraction (NPD), scanning electron microscopy (SEM), low magnetic field and high pulsed magnetic field magnetometry as well as transport measurements. In the present manuscript we will focus on the consequences of such substitution on structural, electronic and magnetic properties. The presented results show the lack of expected enhancement of the Curie temperature by the Lanthanide addition. This puts doubts on the possibility of electron doping in the Sr2CrReO6 system via the standard solid-state reaction growth techniques with rare-earth doping, commonly used for other double perovskite compounds., Financial support by EuroMagNET (under the EU contract RII3-CT- 2004-506239 of the 6th Framework Structuring the European Research Area, Research Infrastructures Action), as well as the Spanish Ministry of Science (through projects FIS08-03951, MAT2005-04562 and MAT2008-06567-C02 including FEDER funding) and the Polish Ministry of Science and Higher Education is also acknowledged.

4 páginas, 6 figuras., We report the structural and magnetotransportproperties of three 300-nm-thick Bithinfilmsgrown on Si (0 0 1) substrates by means of thermalevaporation using different buffer layer (175-nm-thick Si3N4, highly resistive Si and 800-nm-thick SiO2, respectively). X-ray diffraction (XRD) and scanning electron microscopy (SEM) indicate that the Bifilms are polycrystalline with the grains preferentially oriented along the trigonal-axis [0 0 1]. The Bifilm evaporated on SiO2 presents the highest crystallinity which reflects on a higher magnetoresistance value (120% at room temperature and 160% at 2 K and 90 kOe), whereas the lowest magnetoresistance value is found for the Bifilm evaporated on Si3N4 (90% at room temperature and 140% at 2 K and 90 kOe). The magnetic field dependence of the Hall resistivity indicates the presence of both electrons and holes whose contributions strongly depend on the temperature. As a function of temperature, a significant enhancement of the hall resistivity is found below 150 K. Interestingly, the MR values show an enhancement at the same temperature, which indicates changes in the carrier densities and mobilities below 150 K., Financial support by Spanish Ministry of Science(through Projects MAT2005-05565-C02,MAT2008-06567-C02 and MAT2007-65965-02). N. Marcano and M. Plaza acknowledge financial support from Spanish CSIC(JAE-doc program) and CAM.

Diuretic and natriuretic effects of renal dopamine (DA) are well established. However, in volume expansion the pattern of renal DA release into urine (U DA V) and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of U DA V during volume expansion and to characterize the involvement of monoamine-oxidase (MAO) and aromatic amino-acid decarboxylase (AADC) in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control), IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v.) and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.). Results revealed that in C rats U DA V (ng/30 min/100g BWt) increased in the first 30 min expansion from 11.5 ± 1.20 to 21.8 ± 3.10 (p < 0.05) and decreased thereafter. IMAO showed a similar pattern but significantly higher than C at 30 min expansion (32.5 ± 2.20, p < 0.05). IMAO greatly reduced MAO activity from 8.29 ± 0.35 to 1.1 ± 0.03 nmol/mg tissue/hour and significantly increased diuresis and natriuresis over controls. BNZ abolished the early U DA V peak to 3.2±0.72 (p < 0.01) and though, U DA V increased over C after 60 min expansion, natriuresis and diuresis were diminished by BNZ treatment. Results indicate that an increment in renal DA release into urine occurs early in expansion and in a peak-shaped way. In this response MAO plays a predominant role.La dopamina (DA) intrarrenal ejerce efectos diuréticos y natriuréticos. Sin embargo, en los estado de expansión de volumen aún no está bien definido el patrón de liberación de dopamina renal hacia la orina y si cumplen un rol las enzimas involucradas en la síntesis o degradación de la amina. El objetivo del presente trabajo fue determinar el patrón de excreción urinaria de DA (U DA V) durante la expansión de volumen, caracterizando la participación de las enzimas monoaminooxidasa (MAO) y decarboxilasa de aminoácidos aromáticos (AADC) en esta respuesta. Para ello ratas Wistar macho fueron expandidas de volumen con NaCl 0.9% al 5% del peso corporal por hora durante dos horas y divididas en tres grupos, los que al comienzo de la expansión recibieron: C (vehículo, Control), IMAO (Pargilina, inhibidor de MAO, 20 mg/kg PC, i.v.) y BNZ (Benserazida, inhibidor de AADC, 25 mg/kg PC, i.v.). Se observó que en C la U DA V (ng/30min/100gPC) aumentó durante los primeros 30 minutos de expansión de 11.5 ± 1.20 a 21.8 ± 3.10 (p < 0.05), disminuyendo posteriormente. IMAO mostró un patrón de liberación similar pero significativamente mayor que C a los 30 min de expansión (32.5 ± 2.20, p < 0.05). En este grupo la actividad de MAO disminuyó de 8.29 ± 0.35 a 1.1 ± 0.03 nmol/mg tejido/hora y aumentaron la diuresis y natriuresis por sobre los controles. En BNZ, el pico de U DA V observado a los 30 min de la expansión disminuyó a 3.2 ± 0.72 (p < 0.01), aunque luego de 60 minutos fue mayor que en C. BNZ disminuyó tanto la diuresis como la natriuresis. Podemos concluir que al comienzo de la expansión de volumen se produce un pico de excreción de dopamina renal hacia la orina. La enzima MAO juega un rol fundamental en esta respuesta.

Asteraceae is one of the largest families of Angiospermae, and contains the Mikania genus. Several species of this family contain polyacetylenic and thiophenic compounds which are used as taxonomic markers. Also, their phototoxic activity acts as plant defense mechanism. In this paper we report the absence of these compounds in Mikania micrantha.We also describe the composition of the volatile oil from the seeds and inflorescence in the species. Linalool and α-pinene were the main components of this M. micrantha’s essential oil. This study tested the ability of extracts of Mikania micrantha to inhibit the mouse ear inflammation in response to topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA). The antibacterial activity of extracts was also evaluated against Bacillus subtilis and Escherichia coli. Ethyl acetate extracts of this plant exhibited significant antibacterial and anti-inflammatory properties. Therefore, it could be used as a medicinal plant.

The effects of overexpression of the apurinic/apyrimidinic DNA endonuclease Nfo on wet and dry heat and UV-C (254 nm) resistance of Bacillus subtilis spores with or without α/β-type small, acid-soluble spore proteins (SASP) were determined. Results revealed that overexpression of Nfo ≥50-fold in spores increased the wet heat resistance of exoA nfo B. subtilis spores (termed α−β−) that lack most α/β-type SASP, but had no effect on these spores' UV-C resistance. Nfo overexpression also increased these spores' dry heat resistance, and to levels slightly greater than that of wild-type spores. These results are consistent: (1) with wet and dry heat (but not UV-C) generating abasic sites in α−β− spore DNA; (2) with dry heat generating some of these lesions in spores that retain α/β-type SASP; and (3) indicate that Nfo can repair these abasic lesions following spore germination.

A two-dimensional lattice of vortices melts into an isotropic liquid with increasing temperature. A microscopic view of the melting transition reveals that this actually occurs in three steps, one of which is an unusual liquid-crystal-like vortex phase.

A new family of unsaturated isonitriles has been prepared by the base-promoted ring-opening of oxazoles, offering an alternative to the conventional formamide dehydration route. These compounds undergo the full complement of multicomponent reactions for which isonitriles are known and offer the desirable trait of giving amide products that readily participate in acyl substitution reactions (hence, they are convertible). Moreover, they do not have the objectionable odors for which isonitriles are typically known, making them more accessible as reagents for organic synthesis. One focus of the work is isonitriles bearing perfluorinated alkyl groups that enable the ready separation of such reagents from nonfluorinated reaction products using the "light" fluorous method of fluorous solid-phase extraction.

John Kitsuse and Malcolm Spector’s theoretical framework for the analysis of social problems is revisited and an alternative formulation is sketched out, albeit one that maintains a focus on constructivist processes. Spector and Kitsuse’s model posits actors (claims-makers and counter-claimants) who possess moral certitude regarding what is objectionable and worthy of remedial action; by contrast, the present discussion suggests grounding the study of social problems in experiences characterized by uncertainty. The concept of “problematic sociality” is proposed as a way of identifying such circumstances. Sociality — routine, coordinated and manageable forms of association among individuals and between groups — becomes problematic when interactions are experienced as persistently difficult to navigate, distressing, or otherwise viscerally onerous. Encounters with problematic sociality may be connected to underlying social transformations and disruptions. The concept of problematic sociality therefore suggests there is merit in pairing the study of social problems with the study of social change.

We study the origin of the strong difference in the resistivity of focused-electron- and focused-Ga-ion-beam-induced deposition (FEBID and FIBID, resp.) of Pt performed in a dual beam equipment using(CH3)3Pt(CpCH3)as the precursor gas. We have performed in-situ and ex-situ resistance measurements in both types of nanodeposits, finding that the resistivity of Pt by FEBID is typically four orders of magnitude higher than Pt by FIBID. In the case of Pt by FEBID, the current-versus-voltage dependence is nonlinear and the resistance-versus-temperature behavior is strongly semiconducting, whereas Pt by FIBID shows linear current-versus-voltage dependence and only slight temperature dependence. The microstructure, as investigated by high-resolution transmission electron microscopy, consists in all cases of Pt single crystals with size about 3 nm embedded in an amorphous carbonaceous matrix. Due to the semiconducting character of the carbon matrix, which is the main component of the deposit, we propose that the transport results can be mapped onto those obtained in semiconducting materials with different degrees of doping. The different transport properties of Pt by FEBID and FIBID are attributed to the higher doping level in the case of FIBID, as given by composition measurements obtained with energy-dispersive X-ray microanalysis.

Silver/carbon nanoparticle—poly(methyl methacrylate) nanocomposites were obtained by in situ miniemulsion polymerization. It was found by electron microscopy that nanoparticles did not disperse individually but as aggregates; however, notable increments in glass transition temperature in the order of 5 to 15 °C, determined by differential scanning calorimetry, were registered by the addition of small amounts of the nanofiller (0.025, 0.050 or 0.10wt %). Dynamic mechanical analysis indicated gains in mechanical properties, which were related to nanoparticle/polymer interfacial interaction. Results also suggested that dispersion efficiency was a determining aspect in mechanical and thermal performance.

A combined XRD, Mössbauer, SEM, STXM and NMR study of naturally oxidised, ball milled iron powders is presented. The XRD patterns show the peaks of the bcc-Fe phase with the line widths increasing with the milling time. This corresponds to a flattening of the crystallites, as confirmed by SEM, and increased strain due to the accumulation of defects. The effect is consistent with the variation of the Mössbauer line-widths with the milling time. Scanning Transmission Xray Microscopy (STXM) measurements provided oxygen maps of the particles and revealed that the dominant oxide in the nanometric oxide layer is magnetite. The 57Fe spin echo NMR study reveals a dominant signal corresponding to a bcc-Fe core and a much weaker resonance corresponding to a magnetite amount of less than 1%.

Aims: To test whether blood pressure is affected by potassium supplementation which modifies urinary kallikrein (UK) in SHR of either sex, and to elucidate the mechanisms involved. Design: In SHR and WKY blood pressure, renal function and hormonal profile were studied after 1% oral potassium supplementation starting at 4 weeks of age and throughout until 12 weeks of age. Results were compared with those of untreated SHR and WKY of either sex. Results: Systolic blood pressure (mm Hg) started to rise in SHR and was significantly different at 6–8 weeks of age: 153.5 ± 7.9 versus 100 ± 5.6 in female and 157 ± 7.7 versus 98.4 ± 6.8 in male rats (p < 0.01). Systolic blood pressure increased progressively in female and male rats reaching 164.5 ± 4.8 and 204.5 ± 7.6, respectively, at 12 weeks of age. At this time systolic blood pressure was higher in male than in female SHR (p < 0.01) and UK activity (UKa; nkat/day/100 g body weight) was slightly lower in male SHR. After 1% oral potassium supplementation administered from 4 to 12 weeks of age, a decrease in systolic blood pressure was seen in male SHR: 204.5 ± 7.6 versus 173.5 ± 7.9 (p < 0.05); and 164.5 ± 4.8 versus 156.8 ± 5.5 in female rats (NS) at 12 weeks of age, concomitant with an increase in UKa, particularly in male rats (29.35 ± 1.92 versus 36.54 ± 2.61, p < 0.05). As expected, plasma aldosterone (pg/ml), increased markedly after potassium treatment from 129 ± 31.4 in untreated female and male SHR and WKY to 528 ± 180.7 in SHR and 473 ± 88.4 in WKY (p < 0.05 in both cases). After potassium supplementation, potassium excretion was significantly correlated with both aldosterone levels and UKa (p < 0.001 in both cases). No significantly concurrent changes in plasma renin activity were observed, but instead a significant decrease was seen in SHR (p < 0.01). The potassium blood pressure-lowering effect was blunted by aldosterone receptor antagonist treatment that also decreased UKa from 36.5 ± 2.61 to 19.5 ± 1.9, particularly in male SHR. No attempt was made in this experimental setting to block kallikrein or kinin receptors. Conclusions: UKa increases as a consequence of aldosterone stimulation by potassium load since an aldosterone receptor blockade abolishes UKa increment and blood pressure fall. These results further support the hypothesis that the kallikrein kinin system plays a role in blood pressure regulation and they also show a gender different response to potassium load in relation to UKa and blood pressure.

Today, technologies based on magnetic nanoparticles (MNPs) are routinely applied to biological systems with diagnostic or therapeutic purposes. The paradigmatic example is the magnetic resonance imaging (MRI), a technique that uses the magnetic moments of MNPs as a disturbance of the proton resonance to obtain images. Similarly, magnetic fluid hyperthermia (MFH) uses MNPs as heat generators to induce localized cell death. The physical basis of these techniques relies on the interaction with external magnetic fields, and therefore the magnetic moment of the particles has to be maximized for these applications. Targeted drug-delivery based on 'smart' nanoparticles is the next step towards more efficient oncologic therapies, by delivering a minimal dose of drug only to the vicinity of the target. Current improvements in this fields relay on a) particle functionalization with specific ligands for targeting cell membrane recep- tors and b) loading MNPs onto cells (e.g., dendritic cells, T-cells, macrophages) having an active role in tumor grow. Here we review the current state of research on applications of magnetic carriers for cancer therapy, discussing the advances and drawbacks of both passive and targeted delivery of MNPs. The most promising strategies for targeted delivery of MNPs are analyzed, evaluating the expected im- pact on clinical MRI and MFH protocols.

A method for modifying wood fiber with non-solvent media, to produce ready-to-use hydrophobic fiber suitable for use in composites, is proposed in this paper. The chemical modification was achieved by means of a consecutive reaction (cellulose/oxalic acid/cetyl alcohol) performed in a mixing chamber, at 110 °C and 30 rpm. The reaction product was washed by extraction with water and hexanes and then characterized by using spectroscopic techniques (FTIR and 13C CPMAS-NMR). The results from these analyses revealed the presence of C O groups, indicating that the esterification reaction was successful. The thermal stability of the treated samples was studied by thermogravimetric analysis (TGA); the modified fiber exhibited an increased thermal stability relative to the unmodified fiber, this increase may be related to both the formation of ester groups and the grafting of the cetyl radicals.

Piscirickettsiosis is the most prevalent salt-water infectious disease in farmed salmonids in Chile. Antimicrobials are used to treat this disease; however, there is growing concern about the poor response to therapeutants on some fish farms. The objective of this study was to assess whether factors such as type of antibiotic used, average fish weight, temperature at the beginning of the treatment, and mortality at the time of treatment administration affect the probability of treatment failure against piscirickettsiosis. Pen-level treatment and production information for the first treatment event from 2014 pens on 118 farms was used in a logistic mixed model to assess treatment failure. We defined a failed treatment as when the average mortality 3 wk after the treatment was above 0.1%. Farm and company were included in the model as random effects. We found that the antibiotic product, mortality level before the treatment, and fish weight at the start of the treatment all had a significant effect on treatment outcome. Our results suggest that antibiotic treatment success is higher if the treatment is administered when mortality associated with piscirickettsiosis is relatively low. We discuss the effect of weight on treatment success and its potential relationships with husbandry practices and drug pharmacokinetics.

The nature of graphene-metal bonding is crucial for the performance of graphene-based electronic devices. Raman spectroscopy is a powerful technique for probing the electronic behaviour of graphene-metal interfaces. The changes in the Raman spectrum of pristine graphene upon contact with standard metal layers are reported here. In particular, the study is focused on metallization by electron-beam evaporation using chromium or titanium (commonly used as an adhesion layer to improve the bonding of other metals such as gold) and nickel or cobalt (ferromagnetic materials used for spintronics). The results obtained indicate that the main changes in the Raman spectra can be explained in terms of a biaxial strain generated by graphene trying to match the crystalline lattice of the metal. In the case of cobalt, we find that the strong binding of some cobalt atoms to graphene generates a spectrum with a duplication of the characteristic graphene peaks: those corresponding to cobalt physisorbed to graphene and those corresponding to cobalt chemisorbed to graphene, strongly redshifted. Such special behaviour of the graphene-cobalt interface is correlated to the low contact resistance and the enhanced perpendicular magnetic anisotropy of cobalt on graphene., This work was supported by the Spanish Ministry of Economy and Competitivity through project No. MAT2011-27553-C02 including FEDER funds, and by the Aragon Regional Government.

The dependence of Spin Seebeck effect (SSE) with the thickness of the magnetic materials is studied by means of incoherent thermal excitation. The SSE voltage signal in Fe3O4/Pt bilayer structure increases with the magnetic material thickness up to 100 nm, approximately, showing signs of saturation for larger thickness. This dependence is well described in terms of a spin current pumped in the platinum film by the magnon accumulation in the magnetic material. The spin current is generated by a gradient of temperature in the system and detected by the Pt top contact by means of inverse spin Hall effect. Calculations in the frame of the linear response theory adjust with a high degree of accuracy the experimental data, giving a thermal length scale of the magnon accumulation (Λ) of 17 ± 3 nm at 300 K and Λ = 40 ± 10 nm at 70 K., This work was supported by the Spanish Ministry of Science (through Project No. MAT2014-51982-C2-R, including European social fund), the Aragon Regional government (Project No. E26), and Thermo-Spintronic Marie Curie CIG Project (Grant Agreement No. 304043).

Novel tetrahydroindeno[1,2-b]pyrrolidineswereconveniently prepared in moderate to good yields via a sequential Ugi multicomponent reaction or Staudinger/aza-Wittig/Ugi combination, followed by the palladium-catalyzed aerobic oxidative cyclization of the resulting Ugi adducts.

All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.-- et al., We report a systematic study on the thermoelectric performance of spin Seebeck devices based on Fe3O4/Pt junction systems. We explore two types of device geometries: a spin Hall thermopile and spin Seebeck multilayer structures. The spin Hall thermopile increases the sensitivity of the spin Seebeck effect, while the increase in the sample internal resistance has a detrimental effect on the output power. We found that the spin Seebeck multilayers can overcome this limitation since the multilayers exhibit the enhancement of the thermoelectric voltage and the reduction of the internal resistance simultaneously, therefore resulting in significant power enhancement. This result demonstrates that the multilayer structures are useful for improving the thermoelectric performance of the spin Seebeck effect., This work was supported by the Spanish Ministry of Science (through Project Nos. PRI-PIBJP-2011-0794 and MAT2011-27553-C02, including FEDER funding), the Aragón Regional Government (Project No. E26), Thermo-spintronic Marie-Curie CIG (Grant Agreement No. 304043), JST-PRESTO “Phase Interfaces for Highly Ecient Energy Utilization” from JST, Japan, Grant in-Aid for Scientific Research on Innovative Areas “Nano-Spin Conversion Science” (Grant No. 26103005), Grant-in-Aid for Challenging Exploratory Research (Grant No. 26600067), Grant-inAid for Scientific Research (A) (Grant No. 15H02012) from MEXT, Japan, NEC Corporation, and The Noguchi Institute.

Induced effects by direct exposure to ionizing radiation (IR) are a central issue in many fields like radiation protection, clinic diagnosis and oncological therapies. Direct irradiation at certain doses induce cell death, but similar effects can also occur in cells no directly exposed to IR, a mechanism known as bystander effect. Non-IR (radiofrequency waves) can induce the death of cells loaded with MNPs in a focused oncological therapy known as magnetic hyperthermia. Indirect mechanisms are also able to induce the death of unloaded MNPs cells. Using in vitro cell models, we found that colocalization of the MNPs at the lysosomes and the non-increase of the temperature induces bystander effect under non-IR. Our results provide a landscape in which bystander effects are a more general mechanism, up to now only observed and clinically used in the field of radiotherapy., Comment: 16 pages, 4 figures, submitted to International Journal of Radiation Biology

The study of electron-doped Sr 2− x Nd x CrReO 6 half-metallic double perovkites has been carried out. Detailed characterization by means of X-ray diffraction (XRD), scanning electron microscopy (SEM) and magnetization measurements was done. XRD and SEM measurements indicate that the desired stoichiometry is obtained up to Sr substitution around 25%. Magnetization measurements as a function of temperature (up to 800 K) in the Nd-substituted compounds indicate that substantial modification of the Curie temperature does not occur for the investigated level of Nd doping. The values of the saturation magnetization at 5 K for the compounds are consistent with additional electrons being promoted to the conduction band with magnetic moment antiparallel to the localized moment.

We present a study of the power absorption efficiency in several magnetite-based colloids, to asses their potential as magnetic inductive hyperthermia (MIH) agents. Relaxation times τ were measured through the imaginary susceptibility component χ ″ ( T ) , and analyzed within Debye's theory of dipolar fluid. The results indicated Brownian rotational relaxation and allowed to calculate the hydrodynamic radius close to the values obtained from photon correlation. The study of the colloid performances as power absorbers showed no detectable increase of temperature for dextran-coated Fe3O4 nanoparticles, whereas a second Fe3O4-based dispersion of similar concentration could be heated up to 12 K after 30 min under similar experimental conditions. The different power absorption efficiencies are discussed in terms of the magnetic structure of the nanoparticles.

The influence of Zn substitution in the magnetic properties of a nanoscale system Ni 1-x Znfe 2 O 4 (where x = 0.0, 0.25, 0.50 and 0.75) was studied. The ferrites were synthesized by the coprecipitation technique. Transmission electron microscopy revealed a particle size around 4-15 nm, increasing with Zn content. FC/ZFC curves showed a typical superparamagnetic behavior in all samples. It was found that Zn substitution affects both the blocking temperature and the magnetization. The maximum magnetization at room temperature was 48 emu/g for the sample x = 0.50.

We report the magnetotransport properties of a 40nm-thick Fe"3O"4 thin film grown on a MgO (001) substrate by means of pulsed laser deposition, with potential application in Spin Electronics. X-ray diffraction experiments indicate the epitaxial growth with high crystal quality. The resistivity measurements show the anomaly characteristic of the Verwey transition. The magnetoresistance ratios are small as expected for epitaxial Fe"3O"4 thin films and caused by spin-polarized transport through antiphase boundaries. The Hall resistivity is found to be proportional to the magnetization, which strongly suggests that the main contribution comes from the anomalous Hall effect. For the first time on epitaxial Fe"3O"4 thin films, we report the enhancement of the Hall resistivity as the Verwey transition temperature is approached, as had previously been found in bulk single crystals and polycrystalline thick films. Implications of this finding are discussed.

Superparamagnetic hybrid nanoparticles (ca. 80 nm) are obtained. They consist of an inner iron oxide core coated by a silica shell, which is in turn functionalized with amine or carboxyl groups and covalently coupled to a monoclonal antibody (anti-hCG; hCG = human chorionic gonadotropin). The prepared nanoparticles show a specific magnetic moment (per gram of iron) that is comparable to that measured for commercial superparamagnetic iron oxide preparations. The bioactivity of the antibody-conjugated magnetic nanoparticles is verified by a standard bioassay. These results indicate the potential of the hybrid nanoparticles prepared for use as enhanced contrast agents in magnetic resonance imaging applications.

Silver/carbon nanoparticles (9 nm) were incorporated, as reinforcements, into a matrix of poly(methyl methacrylate) via in situ miniemulsion polymerization. It was found by differential scanning calorimetry that the glass-transition temperature of the poly(methyl methacrylate) showed an improvement of 14 °C with only 0.5 wt % nanoparticles in comparison with a pure poly(methyl methacrylate) control, which was also obtained by miniemulsion polymerization under the same conditions. This increase was related to a polymer chain mobility restriction due to a combination of bound plastic and joint plastic shell effects at the interphase and the surrounding regions. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 511–518, 2007.

Blue agave fiber esterification and its use in thermoplastic composite reinforcement was the purpose of this research. Spectroscopic techniques indicated the occurrence of the esterification reaction, since signals for carbonyl groups were found through FT-IR (1750 cm −1 ) and 13 C-CPMAS-NMR (172 ppm). Mechanical properties characterization showed that superficial modification was successfully achieved, since a change in the elastic modulus and improved impact resistance were observed when the modified fiber was used. In addition, electron microscopy studies indicated that the modified fiber produced an enhancement in fiber/HDPE interfacial interaction, since less fiber sliding evidence was observed on the composite surface. The Cox–Merz rule was used as an alternative tool in order to study composites rheometry along an expanded range of shear rate in the power law region.

Spin Seebeck effects (SSEs) have been investigated in highly crystalline magnetic multilayer [Fe3O4/Pt]n films. Voltage as well as power generated by the SSE were found to be significantly enhanced with increasing the number of layers n. This voltage enhancement defies the simple understanding of the SSE and suggests that spin current flowing between the magnetic layers in the thickness direction plays an important role in multilayer SSE systems and the observed voltage enhancement.

Area management, the coordination of production and biosecurity practices across neighboring farms, is an important disease control strategy in aquaculture. Area management in aquaculture escalated in prominence in response to outbreaks of infectious salmon anemia (ISA) internationally. Successes in disease control have been attributed to the separation achieved through area-level synchronized stocking, fallowing, movement restrictions, and fomite or pest control. Area management, however, is costly; often demanding extra biosecurity, lengthy or inconveniently timed fallows, and localization of equipment, personnel, and services. Yet, this higher-order organizational structure has received limited epidemiologic attention. Chile's National Fisheries and Aquaculture Service instigated area management practices in response to the 2007 emergence of ISA virus (ISAV). Longitudinal data simultaneously collected allowed retrospective evaluation of the impact of component tenets on virus control. Spatiotemporal analyses identified hydrographic linkages, shared ports, and fish transfers from areas with recent occurrence of ISAV as the strongest predictors of virus spread between areas, though specifics varied by ISAV type (here categorized as HPR0 for the non-virulent genotypes, and HPRv otherwise). Hydrographic linkages were most predictive in the period before implementation of enhanced biosecurity and fallowing regulations, suggesting that viral load can impact spread dynamics. HPR0 arose late in the study period, so few HPRv events were available by which to explore the hypothesis of HPR0 as progenitor of outbreaks. However, spatiotemporal patterns in HPRv occurrence were predictive of subsequent patterns in HPR0 detection, suggesting a parallel, or dependent, means of spread. Better data precision, breadth and consistency, common challenges for retrospective studies, could improve model fit; and, for HPR0, specification of diagnostic test accuracy would improve interpretation.

We have previously shown that ovariectomy in adult Wistar rats under normal sodium (NS) intake results in an overexpression of total Na+, K+-ATPase α 1subunit (NKA). Upon high sodium (HS) intake ovariectomized (oVx) rats developed a defective NKA phosphorylation, a decrease in sodium excretion, and an increment in mean blood pressure (MBP). Since NKA phosphorylation is modulated by dopamine (DA), the aim of this study was to compare the intracellular response of the renal DA system leading to NKA phosphorylation upon sodium challenge in intact female (IF) and oVx rats. In IF rats HS caused an increase in urinary DA and sodium, in NKA phosphorylation state, in Cytochrome P4504A (CYP4A) expression and in 20-HETE production, while MBP kept normal. Blockade of D1R with the D1-like receptor antagonist SCH23390 in IFHS rats shifted NKA into a more dephosphorylated state, decreased sodium excretion by 50 % and increased MBP. In oVxNS rats, D1R expression was reduced and D3R expression was increased, and under HS intake sodium excretion was lower and MBP higher than in IFHS rats (both p

The amidation of unactivated ethyl esters with achiral and chiral 1,2-amino alcohols under microwave irradiation and base-free conditions is described. This procedure provides a convenient method for the synthesis of β-hydroxyacetamides bearing pyrazole, imidazole, and benzimidazole groups in high yields and without racemization. The protocol described herein is environmentally friendly and allows for the preparation of a wide variety of β-hydroxyacetamides, which are key intermediates in the synthesis of oxazolines and other derivatives of biological interest.

The development of bilateral electronic monitoring (BEM) exemplifies how shifts in the "culture of control" (Garland, 2001), including a focus on domestic violence (DV) victims' emotional welfare and integration into proceedings, can alter abused partners' everyday lives. As a protective strategy, BEM provides DV victims with an alternative to relocating to a shelter. The subjective sense of safety engendered by program involvement emerges gradually, as everyday environments are re-evaluated in light of an estranged partner's absence; through social interactions with family members, friends, and justice agents; and as the understanding of what it means to be "protected" develops. The use of BEM technology to promote victim welfare rather than as a strictly evidentiary tool suggests that this expression of the new paradigm of justice is oriented toward victim re-entry into civil society.

Activated carbon particles were obtained by a solvatation method and added as fillers in cellulose triacetate as polymeric matrix. Various composite films were prepared by solvent casting at different controlled temperature and relative humidity (35–55° C, 10–70% RH) conditions, for three different filler loadings (0, 1 and 3%). Scanning electron microscopy (SEM) images revealed that for slow solvent evaporation rates (low temperature and high RH) a non-agglomerated composite film is achieved. This condition observed in SEM was correlated to the film with the best mechanical properties found by stress-strain and creep tests. Water flux and mechanical resistance is also higher for the membrane obtained at the best synthesis conditions found (M1) (35°C, 70% RH). Contact angle measurements indicated that there is differentiation among membranes of different carbon loading respect to M1, associated to surface homogeneity. Atomic force microscopy (AFM) images showed structural variation among membranes (M1 and its counterpart without carbon) in the nanoscale. Contrast phase AFM analysis exposed homogeneous dispersion of activated carbon particles on membrane M1. Major adhesion between entangled polymer network and activated carbon is postulated as the main factor for the composite polymer proper structural performance. Copyright © 2006 John Wiley & Sons, Ltd.

It has been suggested that an abnormal activity of the hypothalamic-pituitary-adrenal-gonadal axis may be implicated in the pathogenesis of spontaneously hypertensive rats (SHR) blood pressure hypertension. However, it is widely known that the kallikrein-kinin system plays a role in blood pressure regulation in this strain, because an inverse relation between blood pressure and urinary kallikrein excretion has been reported. It was of our interest to study how early suppression of sexual hormones affected blood pressure regulation in SHR and urinary kallikrein excretion and to elucidate the involved mechanisms. For these purpose, SH and Wistar-Kyoto (WKY) rats blood pressure, renal function, and hormonal profile were studied after prepuberal gonadectomy starting at 4 weeks of age throughout until the 12th week of age. Results were compared with those of untreated SH and WKY rats of either sex. The response to blocking agents against aldosterone and kallikrein-kinin system also were evaluated. Systolic blood pressure increased progressively in male and female SHR 12 weeks of age. Systolic blood pressure was higher in male than in female SHR, but urinary kallikrein was lower in male SHR. Prepuberal gonadectomy induced a significant decrease in systolic blood pressure in male and in female SHR at 12 weeks of age, accompanied by an increase in urinary kallikrein in male and in female SHR. Plasma aldosterone increased markedly in female and male SHR after gonadectomy. No concurrent changes in plasma renin activity or corticosterone levels were observed. The aldosterone receptor antagonist and the kallikrein inhibitor treatment blunted the blood pressure lowering effect of gonadectomy and diminished urinary kallikrein excretion. Results support the existence of a sexual dimorphism related to hypertension and urinary kallikrein and suggest an interaction among the kallikrein-kinin system, sexual hormones, and mineralocorticoids in the neonatal programming of hypertension.

Aims: The interplay between natriuretic dopamine and antinatriuretic angiotensin II represents an important mechanism for the regulation of renal sodium and water excretion. Monoamine oxidase is the main metabolizing pathway for dopamine in the renal cortex. In this study, we have analysed the effect of low sodium feeding and AT) receptor blockade on renal dopamine metabolism by monoamine oxidase. Methods: Four groups of rats were studied: 1, normal salt diet (NS); 2, low salt diet (LS); 3, NS receiving Losartan (Los, specific AT) receptor antagonist, 20 mg kg - 1 bwt day - 1 , NS + Los); 4, LS receiving Los (LS + Los). Results: Urinary dopamine excretion was lower in LS than in NS rats (543 ′ 32 vs. 680 ′ 34 ng day - 1 100 g - 1 bwt, P < 0.05). When treated with Los, DOPAC excretion and urinary DOPAC/dopamine ratio fell significantly in the LS + Los group as compared with the LS group (1199 ′ 328 vs. 3081 ′ 681 ng day - 1 100 g - 1 bwt and 1.90 ′ 0.5 vs. 5.7 ′ 1.2, respectively, both P < 0.02). Losartan increased hydroelectrolyte excretion in the LS group. No changes were found in the NS + Los group. Aromatic L-amino acid decarboxylase activity in cortex was similar in NS and LS rats. Instead, monoamine oxidase activity was higher in cortical homogenates from LS rats (in nmol mg tissue - 1 h - 1 : NS 7.66 ′ 0.52; LS 9.82 ′ 0.59, P < 0.05) and this difference was abolished in LS + Los rats (7.34 ′ 0.49 nmol mg tissue - 1 h - 1 , P < 0.01, vs. LS). Conclusions: We have concluded that low levels of dopamine in the urine of LS rats are because of an increase in the activity of renal monoamine oxidase and that angiotensin II mediates this increase through stimulation of AT 1 receptors.

The joint power of neutron diffraction and pressure techniques allows us to characterize under unique conditions th en ature and different role of basic interactions in solids. We have covere dab road phenomenology in archetypical compounds: intermetallics and magnetic oxides. We have selected compounds in which the effect of moderate pressure is able to modify the electronic structure and bond angles that in turn are in the bases of magnetic and structural transitions. Complex magnetic and structural phase diagrams are reported for compounds with magnetic (Tb1−X YX Mn2) and structural (RE5Si4−X GeX ) instabilities. Pressure-induced change of the magnetic structure in (R2Fe17) intermetallics and the effect on the colossal magnetoresistance manganites are described.

Bioferrofluids obtained from carbon coated iron nanoparticles are promising candidates for magnetic drug delivery. The carbon cages render the particles biocompatible, and provide a good support for drug adsorption. We propose a method in which gold plated permanent magnets are implanted directly in the affected organ, close to the tumour, by endoscopic techniques. The bioferrofluid charged with the chemotherapeutic agent is injected and the particles attracted to the magnet, then desorption of the drug takes place at the tumoral region. This method seems to be more promising, costless and effective than that based on the application of external magnetic fields. Preliminary results of drug adsorption and a preclinical experimental animal model are described.