Ferritin nanovehicle for targeted delivery of cytochrome C to cancer cells

In this work, we have exploited the unique properties of a chimeric archaeal-human ferritin to encapsulate, deliver and release cytochrome c and induce apoptosis in a myeloid leukemia cell line. The chimeric protein combines the versatility in 24-meric assembly and cargo incorporation capability of Archaeglobus fulgidus ferritin with specific binding of human H ferritin to CD71, the “heavy duty” carrier responsible for transferrin-iron uptake. Delivery of ferritin-encapsulated cytochrome C to the Acute Promyelocytic Leukemia (APL) NB4 cell line, highly resistant to transfection by conventional methods, was successfully achieved in vitro. The effective liberation of cytochrome C within the cytosolic environment, demonstrated by double fluorescent labelling, induced apoptosis in the cancer cells

Radiogenomics in clear cell renal cell carcinoma: correlations between advanced CT imaging (texture analysis) and microRNAs expression

Purpose: A relevant challenge for the improvement of clear cell renal cell carcinoma management could derive from the identification of novel molecular biomarkers that could greatly improve the diagnosis, prognosis, and treatment choice of these neoplasms. In this study, we investigate whether quantitative parameters obtained from computed tomography texture analysis may correlate with the expression of selected oncogenic microRNAs. Methods: In a retrospective single-center study, multiphasic computed tomography examination (with arterial, portal, and urographic phases) was performed on 20 patients with clear cell renal cell carcinoma and computed tomography texture analysis parameters such as entropy, kurtosis, skewness, mean, and standard deviation of pixel distribution were measured using multiple filter settings. These quantitative data were correlated with the expression of selected microRNAs (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both the evaluations (microRNAs and computed tomography texture analysis) were performed on matched tumor and normal corticomedullar tissues of the same patients cohort. Results: In this pilot study, we evidenced that computed tomography texture analysis has robust parameters (eg, entropy, mean, standard deviation) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression was evidenced in tumor versus normal tissue. Interestingly, entropy and miR-21-5p show promising correlation in clear cell renal cell carcinoma opening to a radiogenomic strategy to improve clear cell renal cell carcinoma management. Conclusion: In this pilot study, a promising correlation between microRNAs and computed tomography texture analysis has been found in clear cell renal cell carcinoma. A clear cell renal cell carcinoma can benefit from noninvasive evaluation of texture parameters in adjunction to biopsy results. In particular, a promising correlation between entropy and miR-21-5p was found

Reflectance anisotropy spectroscopy of strain-engineered GaAsBi alloys

In this paper, we present results obtained by an optical technique, namely, reflectance anisotropy spectroscopy (RAS), applied to a series of GaAs1-xBix samples grown by molecular beam epitaxy (MBE) under different strain conditions with the increasing concentration of Bi, up to the higher value of about 7%. The epitaxial buffer layers for the growing GaAs1-xBix layer were prepared with either a compressive strain (as it is commonly done) or a tensile strain: The latter case has been proven to be a strategy that allows us to obtain a better crystalline quality [Tisbi et al., Phys. Rev. Appl. 14, 014028 (2020)]. A characteristic, well defined anisotropy signal below 2.5 eV is demonstrated to be connected to the presence of Bi and, in particular, to the strain produced in the sub-surface region by the voluminous Bi atoms. The amplitude of this signal directly relates to the Bi quantity, while its sign gives information about the local clustering/ordering of Bi atoms in the grown sample. We conclude that the detailed interpretation of RAS signatures and the knowledge of their origin offer the opportunity to utilize this technique to follow in real time the GaAsBi growth either in MBE or in metal organic vapor phase epitaxy processes

Classical dynamics and stability of collapsing thick shells of matter

We study the collapse towards the gravitational radius of a macroscopic spherical thick shell surrounding an inner massive core. This overall electrically neutral macroshell is composed by many nested delta-like massive microshells which can bear non-zero electric charge, and a possibly non-zero cosmological constant is also included. The dynamics of the shells is described by means of Israel's (Lanczos) junction conditions for singular hypersurfaces and, adopting a Hartree (mean field) approach, an effective Hamiltonian for the motion of each microshell is derived which allows to check the stability of the matter composing the macroshell. We end by briefly commenting on the quantum effects which may arise from the extension of our classical treatment to the semiclassical level.Comment: 16 pages in IOP style, 8 figures, accepted for publication in Class. Quantum Gra

Exploring the Levinthal limit in protein folding

According to the thermodynamic hypothesis, the native state of proteins is uniquely defined by their amino acid sequence. On the other hand, according to Levinthal, the native state is just a local minimum of the free energy and a given amino acid sequence, in the same thermodynamic conditions, can assume many, very different structures that are as thermodynamically stable as the native state. This is the Levinthal limit explored in this work. Using computer simulations, we compare the interactions that stabilize the native state of four different proteins with those that stabilize three non-native states of each protein and find that the nature of the interactions is very similar for all such 16 conformers. Furthermore, an enhancement of the degree of fluctuation of the non-native conformers can be explained by an insufficient relaxation to their local free energy minimum. These results favor Levinthal's hypothesis that protein folding is a kinetic non-equilibrium process.FCT - Foundation for Science and Technology, Portugal [UID/Multi/04326/2013]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientia co e Tecnologico (CNPq

Fabrication and characterization of thin piezoelectric β-poly(vinylidene fluoride) films

The polymer polyvinylidene fluoride (PVDF) has four phases, each characterized by different molecular configurations of the polymer chains. In its beta phase it arranges in an all-trans configuration with dipolar symmetry, exhibiting piezoelectric effects. During the production of thin PVDF films by spin-coating, the polymer chains are not aligned and the dipoles are not oriented. To achieve the desired piezoelectric behavior, it is necessary to optimize both the chain alignment and the dipole orientation processes. We here present an easy procedure to maximize the percentage of the beta phase in the polymer production. The efficiency and reliability of such method has been assessed through Fourier-Transform Infra-Red and Raman spectroscopies, while the morphological differences of the two phases have been analyzed through Scanning Electron Microscopy. The results confirm the efficiency of this method

A coherent triggered search for single spin compact binary coalescences in gravitational wave data

In this paper we present a method for conducting a coherent search for single spin compact binary coalescences in gravitational wave data and compare this search to the existing coincidence method for single spin searches. We propose a method to characterize the regions of the parameter space where the single spin search, both coincident and coherent, will increase detection efficiency over the existing non-precessing search. We also show example results of the coherent search on a stretch of data from LIGO's fourth science run but note that a set of signal based vetoes will be needed before this search can be run to try to make detections.Comment: 14 pages, 4 figure

Reticulon1-C modulates protein disulphide isomerase function

Endoplasmic reticulum (ER) is the primary site for the synthesis and folding of secreted and membrane-bound proteins. Accumulation of unfolded and misfolded proteins in ER underlies a wide range of human neurodegenerative disorders. Hence, molecules regulating the ER stress response represent potential candidates as drug targets for tackling these diseases. Protein disulphide isomerase (PDI) is a chaperone involved in ER stress pathway, its activity being an important cellular defense against protein misfolding. Here, we demonstrate that human neuroblastoma SH-SY5Y cells overexpressing the reticulon protein 1-C (RTN1-C) reticulon family member show a PDI punctuate subcellular distribution identified as ER vesicles. This represents an event associated with a significant increase of PDI enzymatic activity. We provide evidence that the modulation of PDI localization and activity does not only rely upon ER stress induction or upregulation of its synthesis, but tightly correlates to an alteration in its nitrosylation status. By using different RTN1-C mutants, we demonstrate that the observed effects depend on RTN1-C N-terminal region and on the integrity of the microtubule network. Overall, our results indicate that RTN1-C induces PDI redistribution in ER vesicles, and concomitantly modulates its activity by decreasing the levels of its S-nitrosylated form. Thus RTN1-C represents a promising candidate to modulate PDI function