Nanostructured Metallo‐Dielectric Quasi‐Crystals: Towards Photonic‐Plasmonic Resonance Engineering

The first evidence of out‐of‐plane resonances in hybrid metallo‐dielectric quasi‐crystal (QC) nanostructures composed of metal‐backed aperiodically patterned low‐contrast dielectric layers is reported. Via experimental measurements and full‐wave numerical simulations, these resonant phenomena are characterized with specific reference to the Ammann‐Beenker (quasi‐ periodic, octagonal) tiling lattice geometry and the underlying physics is investigated. In particular, it is shown that, by comparison with standard periodic structures, a moderately richer spectrum of resonant modes may be excited, due to the easier achievement of phase‐matching conditions endowed by its denser Bragg spectrum. Such modes are characterized by a distinctive plasmonic or photonic behavior, discriminated by their field distribution and dependence on the metal film thickness. Moreover, the response is accurately predicted via computationally affordable periodic‐approximant‐based numerical modeling. The enhanced capability of QCs to control number, spectral position, and mode distribution of hybrid resonances may be exploited in a variety of possible applications. To assess this aspect, label‐free biosensing is studied via characterization of the surface sensitivity of the proposed structures with respect to local refractive index changes. Moreover, it is also shown that the resonance‐engineering capabilities of QC nanostructures may be effectively exploited in order to enhance the absorption efficiency of thin‐film solar cells.     

Effect of voluntary repetitive long-lasting muscle contraction activity on the BOLD signal as assessed by optimal hemodynamic response function

Objective

Among other neuroimaging techniques, functional magnetic resonance imaging (fMRI) can be useful for studying the development of motor fatigue. The aim of this study was to identify differences in cortical neuronal activation in nine subjects on three motor tasks: right-hand movement with minimum, maximum, and post-fatigue maximum finger flexion.

Materials and methods

fMRI activation maps for each subject and during each condition were obtained by estimating the optimal model of the hemodynamic response function (HRF) out of four standard HRF models and an individual-based HRF model (ibHRF).

Results

ibHRF was selected as the optimal model in six out of nine subjects for minimum movement, in five out of nine for maximum movement, and in eight out of nine for post-fatigue maximum movement. As compared to maximum movement, a large reduction in the total number of active voxels (primary sensorimotor area, supplementary motor area and cerebellum) was observed in post-fatigue maximum movement.

Conclusion

This is the first approach to the evaluation of long-lasting contraction effort in healthy subjects by means of the fMRI paradigm with the use of an individual-based hemodynamic response. The results may be relevant for defining a baseline in future studies on central fatigue in patients with neuropathological disorders.     

NK Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications

Key features of chronic lymphocytic leukemia (CLL) are defects in the immune system and the ability of leukemic cells to evade immune defenses and induce immunosuppression, resulting in increased susceptibility to infections and disease progression. Several immune effectors are impaired in CLL, including T and natural killer (NK) cells. The role of T cells in defense against CLL and in CLL progression and immunotherapy has been extensively studied. Less is known about the role of NK cells in this leukemia, and data on NK cell alterations in CLL are contrasting. Besides studies showing that NK cells have intrinsic defects in CLL, there is a large body of evidence indicating that NK cell dysfunctions in CLL mainly depend on the escape mechanisms employed by leukemic cells. In keeping, it has been shown that NK cell functions, including antibody-dependent cellular cytotoxicity (ADCC), can be retained and/or restored after adequate stimulation. Therefore, due to their preserved ADCC function and the reversibility of CLL-related dysfunctions, NK cells are an attractive source for novel immunotherapeutic strategies in this disease, including chimeric antigen receptor (CAR) therapy. Recently, satisfying clinical responses have been obtained in CLL patients using cord blood-derived CAR-NK cells, opening new possibilities for further exploring NK cells in the immunotherapy of CLL. However, notwithstanding the promising results of this clinical trial, more evidence is needed to fully understand whether and in which CLL cases NK cell-based immunotherapy may represent a valid, alternative/additional therapeutic option for this leukemia. In this review, we provide an overview of the current knowledge about phenotypic and functional alterations of NK cells in CLL and the mechanisms by which CLL cells circumvent NK cell-mediated immunosurveillance. Additionally, we discuss the potential relevance of using NK cells in CLL immunotherapy.     

Nitrogen concentration and nitrate/ammonium ratio affect yield and change the oxalic acid concentration and fatty acid profile of purslane (Portulaca oleracea L.) grown in a soilless culture system

Purslane is an excellent source of omega‐3 fatty acids, amino acids and vitamins. The aim of this research was to study the effect of different nitrogen levels and NO₃⁻‐N/NH₄⁺‐N ratios in the nutrient solution on the yield and on the oxalic acid content and fatty acid profile in purslane grown in a soilless culture system. Two experiments were carried out to test different levels of nitrogen: (1) 8–12–16 mmol L⁻¹ and (2) 0–12–24–36 mmol L⁻¹. A third experiment was carried out maintaining the N level fixed (12 mmol L⁻¹) but varying the NO₃⁻‐N/NH₄⁺‐N ratio: 60:40, 40:60, 0:100. The results indicated that plants grew with increasing nitrogen level up to 36 mmol L⁻¹. Nitrogen supplied in both NO₃⁻ and NH₄⁺ forms produced bigger plants than N supplied in NH₄⁺ form only. Nitrogen did not significantly influence the polyunsaturated fatty acid content in the canopy. Significant trends were found for α‐linolenic acid (LNA; 18:3 n‐3) and linoleic acid (LA; 18:2 n‐6), indicating a favorable accumulation of omega‐3 fatty acids with increasing N; palmitic acid decreased by increasing N and by switching the NO₃⁻/NH₄⁺ ratio towards the NH₄⁺ level in the nutrient solution, but using 0:100 NO₃⁻/NH₄⁺, decreased plant quality. Increasing N lowered oxalic acid production and palmitic acid content, enhancing purslane nutritional quality. Keeping a high N level in the nutrient solution with a 40:60 NO₃⁻/NH₄⁺ ratio would give the best results in terms of yield, oxalic acid concentration and fatty acid profile. Copyright © 2006 Society of Chemical Industry     

Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation

Breast cancer is the most frequent cancer in women worldwide and late diagnosis often adversely affects the prognosis of the disease. Radiotherapy is commonly used to treat breast cancer, reducing the risk of recurrence after surgery. However, the eradication of radioresistant cancer cells, including cancer stem cells, remains the main challenge of radiotherapy. Recently, lipid droplets (LDs) have been proposed as functional markers of cancer stem cells, also being involved in increased cell tumorigenicity. LD biogenesis is a multistep process requiring various enzymes, including Diacylglycerol acyltransferase 2 (DGAT2). In this context, we evaluated the effect of PF-06424439, a selective DGAT2 inhibitor, on MCF7 breast cancer cells exposed to X-rays. Our results demonstrated that 72 h of PF-06424439 treatment reduced LD content and inhibited cell migration, without affecting cell proliferation. Interestingly, PF-06424439 pre-treatment followed by radiation was able to enhance radiosensitivity of MCF7 cells. In addition, the combined treatment negatively interfered with lipid metabolism-related genes, as well as with EMT gene expression, and modulated the expression of typical markers associated with the CSC-like phenotype. These findings suggest that PF-06424439 pre-treatment coupled to X-ray exposure might potentiate breast cancer cell radiosensitivity and potentially improve the radiotherapy effectiveness.     

In situ growth of well-dispersed CdS nanocrystals in semiconducting polymers

A straight synthetic route to fabricate hybrid nanocomposite films of well-dispersed CdS nanocrystals (NCs) in poly[2-methoxy-5-(2''-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) is reported. A soluble cadmium complex [Cd(SBz)₂]₂·MI, obtained by incorporating a Lewis base (1-methylimidazole, MI) on the cadmium bis(benzyl)thiol, is used as starting reagent in an in situ thermolytic process. CdS NCs with spherical shape nucleate and grow well below 200°C in a relatively short time (30 min). Photoluminescence spectroscopy measurements performed on CdS/MEH-PPV nanocomposites show that CdS photoluminescence peaks are totally quenched inside MEH-PPV, if compared to CdS/PMMA nanocomposites, as expected due to overlapping of the polymer absorption and CdS emission spectra. The CdS NCs are well-dispersed in size and homogeneously distributed within MEH-PPV matrix as proved by transmission electron microscopy. Nanocomposites with different precursor/polymer weight ratios were prepared in the range from 1:4 to 4:1. Highly dense materials, without NCs clustering, were obtained for a weight/weight ratio of 2:3 between precursor and polymer, making these nanocomposites particularly suitable for optoelectronic and solar energy conversion applications.     

A Synthetic MUC1 Glycopeptide Bearing βGalNAc‐Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells

This study presents the synthesis of the novel protected O‐glycosylated amino acid derivatives 1 and 2 , containing βGalNAc‐SerOBn and βGalNAc‐ThrOBn units, respectively, as mimetics of the natural Tn antigen (αGalNAc‐Ser/Thr), along with the solid‐phase assembly of the glycopeptides NHAcSer‐Ala‐Pro‐Asp‐Thr[αGalNAc]‐Arg‐Pro‐Ala‐Pro‐Gly‐BSA ( 3 ‐BSA) and NHAcSer‐Ala‐Pro‐Asp‐Thr[βGalNAc]‐Arg‐Pro‐Ala‐Pro‐Gly‐BSA ( 4 ‐BSA), bearing αGalNAc‐Thr or βGalNAc‐Thr units, respectively, as mimetics of MUC1 tumor mucin glycoproteins. According to ELISA tests, immunizations of mice with βGalNAc‐glycopeptide 4 ‐BSA induced higher sera titers (1:320 000) than immunizations with αGalNAc‐glycopeptide 3 ‐BSA (1:40 000). Likewise, flow cytometry assays showed higher capacity of the obtained anti‐glycopeptide 4 ‐BSA antibodies to recognize MCF‐7 tumor cells. Cross‐recognition between immunopurified anti‐βGalNAc antibodies and αGalNAc‐glycopeptide and vice versa was also verified. Lastly, molecular dynamics simulations and surface plasmon resonance (SPR) showed that βGalNAc‐glycopeptide 4 can interact with a model antitumor monoclonal antibody (SM3). Taken together, these data highlight the improved immunogenicity of the unnatural glycopeptide 4 ‐BSA, bearing βGalNAc‐Thr as Tn antigen isomer.     

High SPARC Expression Starting from Dysplasia,Associated with Breast Carcinoma,Is Predictive for Bone Metastasis without Enhancement of Plasma Levels

In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ET_AR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ET_AR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ET_AR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer.