Adeno-associated virus (AAV) vectors are currently the leading candidates for virus-based gene therapies because of their broad tissue tropism, non-pathogenic nature and low immunogenicity. They have ...been successfully used in clinical trials to treat hereditary diseases such as haemophilia B (ref. 2), and have been approved for treatment of lipoprotein lipase deficiency in Europe. Considerable efforts have been made to engineer AAV variants with novel and biomedically valuable cell tropisms to allow efficacious systemic administration, yet basic aspects of AAV cellular entry are still poorly understood. In particular, the protein receptor(s) required for AAV entry after cell attachment remains unknown. Here we use an unbiased genetic screen to identify proteins essential for AAV serotype 2 (AAV2) infection in a haploid human cell line. The most significantly enriched gene of the screen encodes a previously uncharacterized type I transmembrane protein, KIAA0319L (denoted hereafter as AAV receptor (AAVR)). We characterize AAVR as a protein capable of rapid endocytosis from the plasma membrane and trafficking to the trans-Golgi network. We show that AAVR directly binds to AAV2 particles, and that anti-AAVR antibodies efficiently block AAV2 infection. Moreover, genetic ablation of AAVR renders a wide range of mammalian cell types highly resistant to AAV2 infection. Notably, AAVR serves as a critical host factor for all tested AAV serotypes. The importance of AAVR for in vivo gene delivery is further highlighted by the robust resistance of Aavr(-/-) (also known as Au040320(-/-) and Kiaa0319l(-/-)) mice to AAV infection. Collectively, our data indicate that AAVR is a universal receptor involved in AAV infection.
In nanomedicine, hybrid nanomaterials stand out for providing new insights in both the diagnosis and treatment of several diseases. Once administered, engineered nanoparticles (NPs) interact with ...biological molecules, and the nature of this interaction might directly interfere with the biological fate and action of the NPs. In this work, we synthesized a hybrid magnetic nanostructure, with antibacterial and antitumoral potential applications, composed of a magnetite core covered by silver NPs, and coated with a modified chitosan polymer. As magnetite NPs readily oxidize to maghemite, we investigated the structural properties of the NPs after addition of the two successive layers using Mössbauer spectroscopy. Then, the structural characteristics of the NPs were correlated to their interaction with albumin, the major blood protein, to evidence the consequences of its binding on NP properties and protein retention. Thermodynamic parameters of the NPs–albumin interaction were determined. We observed that the more stable NPs (coated with modified chitosan) present a lower affinity for albumin in comparison to pure magnetite and magnetite/silver hybrid NPs. Surface properties were key players at the NP–biological interface. To the best of our knowledge, this is the first study that demonstrates a correlation between the structural properties of complex hybrid NPs and their interaction with albumin.
The authors describe the design and implementation of a large multiethnic cohort established to study diet and cancer in the United States. They detail the source of the subjects, sample size, ...questionnaire development, pilot work, and approaches to future analyses. The cohort consists of 215,251 adult men and women (age 45–75 years at baseline) living in Hawaii and in California (primarily Los Angeles County) with the following ethnic distribution: African-American (16.3%), Latino (22.0%), Japanese-American (26.4%), Native Hawaiian (6.5%), White (22.9%), and other ancestry (5.8%). From 1993 to 1996, participants entered the cohort by completing a 26-page, self-administered mail questionnaire that elicited a quantitative food frequency history, along with demographic and other information. Response rates ranged from 20% in Latinos to 49% in Japanese-Americans. As expected, both within and among ethnic groups, the questionnaire data show substantial variations in dietary intakes (nutrients as well as foods) and in the distributions of non-dietary risk factors (including smoking, alcohol consumption, obesity, and physical activity). When compared with corresponding ethnic-specific cancer incidence rates, the findings provide tentative support for several current dietary hypotheses. As sufficient numbers of cancer cases are identified through surveillance of the cohort, dietary and other hypotheses will be tested in prospective analyses. Am J Epidemiol 2000;151:346–57.
Magnetic, compositional, and morphological properties of Zn–Fe-oxide core–shell bimagnetic nanoparticles were studied for three samples with 0.00, 0.06, and 0.10 Zn/Fe ratios, as obtained from ...particle-induced X-ray emission analysis. The bimagnetic nanoparticles were produced in a one-step synthesis by the thermal decomposition of the respective acetylacetonates. The nanoparticles present an average particle size between 25 and 30 nm as inferred from transmission electron microscopy (TEM). High-resolution TEM images clearly show core–shell morphology for the particles in all samples. The core is composed by an antiferromagnetic (AFM) phase with a Wüstite (Fe1–y O) structure, whereas the shell is composed by a Zn x Fe3–x O4 ferrimagnetic (FiM) spinel phase. Despite the low solubility of Zn in the Wüstite, electron energy-loss spectroscopy analysis indicates that Zn is distributed almost homogeneously in the whole nanoparticle. This result gives information on the formation mechanisms of the particle, indicating that the Wüstite is formed first, and the superficial oxidation results in the FiM ferrite phase with similar Zn concentration than the core. Magnetization and in-field Mössbauer spectroscopy of the Zn-richest nanoparticles indicate that the AFM phase is strongly coupled to the FiM structure of the ferrite shell, resulting in a bias field (H EB) appearing below T N FeO, with HEB values that depend on the core–shell relative proportion. Magnetic characterization also indicates a strong magnetic frustration for the samples with higher Zn concentration, even at low temperatures.
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•Coercivity of the α′-martensite is characterized by strong magnetic shape anisotropy.•α′ → γ transformation is split into two stages during continuous annealing.•Magnetic properties ...present an annealing time-dependence between 500 and 600 °C.•Formation of γ-nanograins in the early stages of reversion induces strong magnetic shape anisotropy.•Athermal α′-formation within the prior athermal ε-phase is observed for temperatures lower than 100 °C.
Strain-induced martensite (SIM) formation was evaluated upon cold-rolling of a 17.6 wt.%Mn-TRIP steel by means of magnetic measurements, X-ray diffraction, and high-resolution electron backscatter diffraction (EBSD). α′-martensite formation was observed to be dependent on the presence of prior ε-martensite. Upon deformation, the coercivity of the ferromagnetic α′-martensite is characterized by strong magnetic shape anisotropy. Austenite (γ) reversion was evaluated by means of in situ magnetic measurements during continuous annealing. The experimental results were compared to thermodynamic simulations. It turned out that γ-reversion was not completed in the regime where a γ-single phase field is expected, which suggests the splitting of α′ → γ transformation into two stages. The Curie temperature of remaining α′-martensite was determined as being ∼620 °C. Magnetic properties presented an annealing time-dependence within the temperature range of 500–600 °C, suggesting long-range diffusional α′ → γ transformation. With the aid of electron channeling contrast image technique (ECCI), we noticed that the formation of γ-nanograins in the early stages of reversion is sufficient to induce strong magnetic shape anisotropy in this steel. After full austenitization at 800 °C, further in situ magnetic measurements were also used to track the magnetic response of the material upon controlled cooling. Athermal formation of α′-martensite within the prior athermal ε-phase was clearly observed for temperatures lower than 100 °C. Using thermodynamic modeling we also calculated the start temperature for ε-formation (Msε). Results showed that ε-martensite is indeed expected to form before α′, which was confirmed in all cases by means of EBSD.
•Fe-doped ITO combines the good electrical, transparent and magnetic properties.•The surface-disorder Raman modes are quenched due to the high laser power source.•Mossbauer measurements provide ...information about Sn4+-ions in the crystalline sites.•Fe-doped ITO displays an AFM occurrence of the iron ions in a paramagnetic phase.•The sheet resistance shows a monotonous increase as the Fe content is increased.
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Fe-doped indium tin oxide (ITO) is an exciting material because it combines the host matrix's good electrical conductivity with the magnetic properties coming from the most earth-abundant transition metal, Fe. In this regard, a single-pot synthesis route based on a polymeric precursor method has been used to produce high-quality undoped and iron-doped ITO with iron content up to 13.0 mol%. The crystal formation in the bixbyite-type structure of all samples is confirmed by X-ray diffraction data analysis. A monotonous decrease of the lattice parameters with the increase of the Fe content is determined, which is consistent with of Fe ions with an oxidation state of 3+ in agreement with the ionic radii difference between In3+ and Fe3+. Raman spectroscopy confirms the bixbyite structure formation and provides evidence of a high surface disorder. 119Sn Mössbauer spectroscopy reveals the formation of only Sn4+ ions. Meanwhile, 57Co Mössbauer spectroscopy suggests the presence of Fe3+ ions in a paramagnetic state. DC magnetization characterization of the Fe-doped ITO nanoparticles confirms the compound's paramagnetic character. The sheet resistance (R/□) measurements provide a lower value for the undoped ITO sample (~0.26 Ω/sq) than the one of commercial bulk material. It has been determined that the sheet resistance increases with the Fe content, suggesting the decrease of the conduction electrons density as the iron content is increased.
Nanoparticles were prepared from a NdFeB-based alloy using the hydrogen decrepitation process together with high-energy ball milling and tested as heating agent for magnetic hyperthermia. In the ...milling time range evaluated (up to 10 h), the magnetic moment per mass at H = 1.59 MA m(-1) is superior than 70 A m(2) kg(-1); however, the intrinsic coercivity might be inferior than 20 kA m(-1). The material presents both ferromagnetic and superparamagnetic particles constituted by a mixture of phases due to the incomplete disproportionation reaction of Nd(2)Fe(14)BH(x) during milling. Solutions prepared with deionized water and magnetic particles exposed to an AC magnetic field (H(max) ~ 3.7 kA m(-1) and f = 228 kHz) exhibited 26 K ≤ ΔT(max) ≤ 44 K with a maximum estimated specific absorption rate (SAR) of 225 W kg(-1). For the pure magnetic material milled for the longest period of time (10 h), the SAR was estimated as ~2500 W kg(-1). In vitro tests indicated that the powders have acceptable cytotoxicity over a wide range of concentration (0.1-100 µg ml(-1)) due to the coating applied during milling.
Superparamagnetic iron oxide nanoparticles (SPIONs) are interesting for biomedical applications in cancer treatment via magneto-hyperthermia. Its potential application contrasts with the challenges ...in producing systems with chemical and morphological uniformity and colloidal stability using simple, low-cost, and sustainable routes. Aqueous syntheses usually fail to control morphology and composition because SPIONs formation mechanisms are not fully understood. Here, we propose an aqueous route to synthesize SPIONs based on the controlled and stoichiometric reduction in situ of Fe3+ to Fe2+ ions in the presence of sulfite ions, followed by aging at 90 ∘C in an alkaline medium for 18 h. SPIONs with high water-stable and controlled characteristics in a sustainable, inexpensive, and scalable procedure were obtained. The nucleation, growth, and hydrolysis rates were adjusted by the excess of OH− ions, initial temperature, and iron precursor nature. The results are discussed concerning concepts of the classical and nonclassical nucleation theories, indicating an optimum pH of 9.5–10.5 for SPIONs formation. The SPIONs present an average size of 11 nm, narrow size distribution, and magnetite phase with about 34 mol% of maghemite due to structural defects. Nanoparticles are superparamagnetic, have a hydrodynamic diameter of 130 nm with a surface potential of ~ −40 mV (pH ≥ 7), and suitable magneto-hyperthermic properties fro cancer treatment. Specific Absorption Rate values were evaluated concerning the SPIONs physical-chemical properties, indicating a strong dependence on the average crystallite size and the magnetization at 250 Oe. Cell viability tests showed that SPIONs did not provide any significant change in cellular growth at used concentrations.
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In this work, we have focused on the size dependence of the magnetic properties and the surface effects of CoFe2O4 nanoparticles synthesized by high-temperature chemical method with diameter d~2, ...4.5, and 7nm, with narrow size distribution. transmission electron microscopy (TEM) images and X-ray diffraction (XRD) profiles indicates that samples with 7 and 4.5nm present a high crystallinity while the 2nm sample has a poor one. We have investigated by magnetization measurements and in-field Mössbauer spectroscopy the influence of the surface in the internal magnetic order of the particles. Particles with d=7nm have almost single domain behavior and the monodomain occupies approximately the whole particle. In the sample with d=4.5nm the surface anisotropy is large enough to alter the ferrimagnetic order in the particle shell. Then, a surface/volume ratio of ~60% is the crossover between a single domain nanoparticle and a frustrated order in a magnetic core–shell structure, due to the competition between surface anisotropy and exchange interaction+crystalline anisotropy in cobalt ferrite. In the d=2nm sample the poor crystallinity and the large surface/volume ratio avoid the ferrimagnetic order in the particle down to T=5K.
•This article analyzes the results of magnetization and Mössbauer spectroscopy measurements of cobalt ferrite (CoFe2O4) nanoparticles with different sizes.•Three samples with different sizes (and narrow size distribution) from 2nm to 7nm have been studied.•A clear evidence of the existence of magnetic disorder at the particle surface in 2nm and 4.5nm nanoparticles is reported.•The surface effect in this magnetic disorder as a function of nanoparticle size is discussed.
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