Chemical stratification in the atmosphere of Ap star HD 133792. Regularized solution of the vertical inversion problem

High spectral resolution studies of cool Ap stars reveal conspicuous anomalies of the shape and strength of many absorption lines. This is a signature of large atmospheric chemical gradients produced by the selective radiative levitation and gravitational settling of chemical species. Here we present a new approach to mapping the vertical chemical structures in stellar atmospheres. We have developed a regularized chemical inversion procedure that uses all information available in high-resolution stellar spectra. The new technique for the first time allowed us to recover chemical profiles without making a priori assumptions about the shape of chemical distributions. We have derived average abundances and applied the vertical inversion procedure to the high-resolution VLT UVES spectra of the weakly magnetic, cool Ap star HD 133792. Our analysis yielded improved estimates of the atmospheric parameters of HD 133792. We show that this star has negligible vsini and the mean magnetic field modulus =1.1+/-0.1 kG. We have derived average abundances for 43 ions and obtained vertical distributions of Ca, Si, Mg, Fe, Cr, and Sr. All these elements except Mg show high overabundance in the deep layers and solar or sub-solar composition in the upper atmosphere of HD 133792. In contrast, the Mg abundance increases with height. We find that transition from the metal-enhanced to metal-depleted zones typically occurs in a rather narrow range of depths in the atmosphere of HD 133792. Based on the derived photospheric abundances, we conclude that HD 133792 belongs to the rare group of evolved cool Ap stars, which possesses very large Fe-peak enhancement, but lacks a prominent overabundance of the rare-earth elements.Comment: Accepted by A&A; 12 pages, 9 figure

Low-temperature gas opacity - AESOPUS: a versatile and quick computational tool

We introduce a new tool - AESOPUS: Accurate Equation of State and OPacity Utility Software - for computing the equation of state and the Rosseland mean (RM) opacities of matter in the ideal gas phase. Results are given as a function of one pair of state variables, (i.e. temperature T in the range 3.2 <= log(T) <= 4.5, and parameter R= rho/(T/10^6 K)^3 in the range -8 <= log(R) <= 1), and arbitrary chemical mixture. The chemistry is presently solved for about 800 species, consisting of almost 300 atomic and 500 molecular species. The gas opacities account for many continuum and discrete sources, including atomic opacities, molecular absorption bands, and collision-induced absorption. Several tests made on AESOPUS have proved that the new opacity tool is accurate in the results,flexible in the management of the input prescriptions, and agile in terms of computational time requirement. We set up a web-interface (http://stev.oapd.inaf.it/aesopus) which enables the user to compute and shortly retrieve RM opacity tables according to his/her specific needs, allowing a full degree of freedom in specifying the chemical composition of the gas. Useful applications may regard RM opacities of gas mixtures with i) scaled-solar abundances of metals, choosing among various solar mixture compilations available in the literature; ii) varying CNO abundances, suitable for evolutionary models of red and asymptotic giant branch stars and massive stars in the Wolf-Rayet stages; iii) various degrees of enhancement in alpha-elements, and C-N, Na-O and Mg-Al abundance anti-correlations, necessary to properly describe the properties of stars in early-type galaxies and Galactic globular clusters; iv) zero-metal abundances appropriate for studies of gas opacity in primordial conditions.Comment: 32 pages, 34 postscript figures, A&A in press; new section 4.1.2 showing first tests with stellar models, sections 2.2, 2.2.2 and 5 expanded; interactive web-page at http://stev.oapd.inaf.it/aesopu

The miR-27a/FOXJ3 Axis Dysregulates Mitochondrial Homeostasis in Colorectal Cancer Cells

miR-27a plays a driver role in rewiring tumor cell metabolism. We searched for new miR-27a targets that could affect mitochondria and identified FOXJ3, an apical factor of mitochondrial biogenesis. We analyzed FOXJ3 levels in an in vitro cell model system that was genetically modified for miR-27a expression and validated it as an miR-27a target. We showed that the miR-27a/FOXJ3 axis down-modulates mitochondrial biogenesis and other key members of the pathway, implying multiple levels of control. As assessed by specific markers, the miR-27a/FOXJ3 axis also dysregulates mitochondrial dynamics, resulting in fewer, short, and punctate organelles. Consistently, in high miR-27a-/low FOXJ3-expressing cells, mitochondria are functionally characterized by lower superoxide production, respiration capacity, and membrane potential, as evaluated by OCR assays and confocal microscopy. The analysis of a mouse xenograft model confirmed FOXJ3 as a target and suggested that the miR-27a/FOXJ3 axis affects mitochondrial abundance in vivo. A survey of the TCGA-COADREAD dataset supported the inverse relationship of FOXJ3 with miR-27a and reinforced cellular component organization or biogenesis as the most affected pathway. The miR-27a/FOXJ3 axis acts as a central hub in regulating mitochondrial homeostasis. Its discovery paves the way for new therapeutic strategies aimed at restraining tumor growth by targeting mitochondrial activities

Broadband Transmission Loss Due to Reverberant Excitation

The noise transmission characteristics of candidate curved aircraft sidewall panel constructions is examined analytically using finite element models of the selected panel geometries. The models are validated by experimental modal analyses and transmission loss testing. The structural and acoustic response of the models are then examined when subjected to random or reverberant excitation, the simulation of which is also discussed. For a candidate curved honeycomb panel, the effect of add-on trim panel treatments is examined. Specifically, two different mounting configurations are discussed and their effect on the transmission loss of the panel is presented. This study finds that the add-on acoustical treatments do improve on the primary structures transmission loss characteristics, however, much more research is necessary to draw any valid conclusions about the optimal configuration for the maximum noise transmission loss. This paper describes several directions for the extension of th..

Development of High-Loading Trastuzumab PLGA Nanoparticles: A Powerful Tool Against HER2 Positive Breast Cancer Cells

Tania Mariastella Caputo,1,&ast; Giovannina Barisciano,2,&ast; Chiara Mulè,1 Angela Maria Cusano,3 Anna Aliberti,1 Livio Muccillo,2 Vittorio Colantuoni,2 Lina Sabatino,2 Andrea Cusano1,3 1Optoelectronics Group, Department of Engineering, University of Sannio, Benevento, Italy; 2Department of Sciences and Technologies, University of Sannio, Benevento, Italy; 3CeRICTscrl Regional Center Information Communication Technology, Benevento, Italy&ast;These authors contributed equally to this workCorrespondence: Anna Aliberti; Lina Sabatino, Email [email protected]; [email protected]: Trastuzumab, a therapeutic monoclonal antibody directed against HER2, is routinely used to treat HER2-positive breast cancer with a good response rate. However, concerns have arisen in the clinical practice due to adverse side effects. One way to overcome these limitations is to encapsulate trastuzumab in nanoparticles to improve cytotoxic activity, increase intracellular drug concentrations, escape the immune system and avoid systemic degradation of the drug in vivo.Methods: A double emulsion method was used to encapsulate trastuzumab into poly(lactic-co-glycolic) nanoparticles, effective for their biocompatibility and biodegradability. These nanocarriers, hereafter referred to as TZPs, were characterised in terms of size, homogeneity, zeta potential and tested for their stability and drug release kinetics. Finally, the TZPs cytotoxicity was assessed in vitro on the HER2 positive SKBR3 breast cancer cell line and compared to free trastuzumab.Results: The TZPs were stable, homogeneous in size, with a reduced zeta potential. They showed higher encapsulation efficiency and drug loading, a prolonged trastuzumab release kinetics that retained its physicochemical properties and functionality. TZPs showed a stronger cytotoxicity and increased apoptosis than similar doses of free trastuzumab in the cell line analysed. Confocal microscopy and flow cytometry assessed TZPs and trastuzumab cellular uptake while Western blot evaluated downstream signalling, overall HER2 content and shedding.Conclusion: TZPs exert more robust effects than free trastuzumab via a dual mode of action: TZPs are taken up by cells through an endocytosis mechanism and release the drug intracellularly for longer time. Additionally, the TZPs that remain in the extracellular space release trastuzumab which binds to the cognate receptor and impairs downstream signalling. This is the sole modality used by free trastuzumab. Remarkably, half dose of TZPs is as efficacious as the highest dose of free drug supporting their possible use for drug delivery in vivo. Keywords: PLGA nanoparticles, double-emulsion method, trastuzumab, breast cancer, signaling transductio

Transcriptomic Analysis of Colorectal Cancer Cells Treated with Oil Production Waste Products (OPWPs) Reveals Enrichment of Pathways of Mitochondrial Functionality

Oil production waste products (OPWPs) derive from olive mill and represent a crucial environmental problem due to their high polyphenolic content able to pollute the ground. One option to reduce the OPWPs’ environmental impact is to exploit polyphenols’ biological properties. We sought to analyze the transcriptomic variations of colorectal cancer cells exposed to the OPWPs extracts and hydroxytyrosol, the major component, to recognize unknown and ill-defined characteristics. Among the top affected pathways identified by GSEA, we focused on oxidative phosphorylation in an in vitro system. Colorectal cancer HCT116 and LoVo cells treated with hydroxytyrosol or OPWPs extracts showed enhancement of the respiratory chain complexes’ protein levels, ATP production and membrane potential, suggesting stimulation of mitochondrial functions. The major proteins involved in mitochondrial biogenesis and fusion events of mitochondrial dynamics were positively affected, as by Western blot, fostering increase of the mitochondrial mass organized in a network of elongated organelles. Mechanistically, we proved that PPARγ mediates the effects as they are mimicked by a specific ligand and impaired by a specific inhibitor. OPWP extracts and hydroxytyrosol, thus, promote mitochondrial functionality via a feed-forward regulatory loop involving the PPARγ/PGC-1α axis. These results support their use in functional foods and as adjuvants in cancer therapy

Combined SERS-Raman screening of HER2-overexpressing or silenced breast cancer cell lines

Abstract Background Breast cancer (BC) is a heterogeneous neoplasm characterized by several subtypes. One of the most aggressive with high metastasis rates presents overexpression of the human epidermal growth factor receptor 2 (HER2). A quantitative evaluation of HER2 levels is essential for a correct diagnosis, selection of the most appropriate therapeutic strategy and monitoring the response to therapy. Results In this paper, we propose the synergistic use of SERS and Raman technologies for the identification of HER2 expressing cells and its accurate assessment. To this end, we selected SKBR3 and MDA-MB-468 breast cancer cell lines, which have the highest and lowest HER2 expression, respectively, and MCF10A, a non-tumorigenic cell line from normal breast epithelium for comparison. The combined approach provides a quantitative estimate of HER2 expression and visualization of its distribution on the membrane at single cell level, clearly identifying cancer cells. Moreover, it provides a more comprehensive picture of the investigated cells disclosing a metabolic signature represented by an elevated content of proteins and aromatic amino acids. We further support these data by silencing the HER2 gene in SKBR3 cells, using the RNA interference technology, generating stable clones further analysed with the same combined methodology. Significant changes in HER2 expression are detected at single cell level before and after HER2 silencing and the HER2 status correlates with variations of fatty acids and downstream signalling molecule contents in the context of the general metabolic rewiring occurring in cancer cells. Specifically, HER2 silencing does reduce the growth ability but not the lipid metabolism that, instead, increases, suggesting that higher fatty acids biosynthesis and metabolism can occur independently of the proliferating potential tied to HER2 overexpression. Conclusions Our results clearly demonstrate the efficacy of the combined SERS and Raman approach to definitely pose a correct diagnosis, further supported by the data obtained by the HER2 gene silencing. Furthermore, they pave the way to a new approach to monitor the efficacy of pharmacologic treatments with the aim to tailor personalized therapies and optimize patients’ outcome

Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism

The circadian gene Timeless (TIM) provides a molecular bridge between circadian and cell cycle/DNA replication regulatory systems and has been recently involved in human cancer development and progression. However, its functional role in colorectal cancer (CRC), the third leading cause of cancer-related deaths worldwide, has not been fully clarified yet. Here, the analysis of two independent CRC patient cohorts (total 1159 samples) reveals that loss of TIM expression is an unfavorable prognostic factor significantly correlated with advanced tumor stage, metastatic spreading, and microsatellite stability status. Genome-wide expression profiling, in vitro and in vivo experiments, revealed that TIM knockdown induces the activation of the epithelial-to-mesenchymal transition (EMT) program. Accordingly, the analysis of a large set of human samples showed that TIM expression inversely correlated with a previously established gene signature of canonical EMT markers (EMT score), and its ectopic silencing promotes migration, invasion, and acquisition of stem-like phenotype in CRC cells. Mechanistically, we found that loss of TIM expression unleashes ZEB1 expression that in turn drives the EMT program and enhances the aggressive behavior of CRC cells. Besides, the deranged TIM-ZEB1 axis sets off the accumulation of DNA damage and delays DNA damage recovery. Furthermore, we show that the aggressive and genetically unstable 'CMS4 colorectal cancer molecular subtype' is characterized by a lower expression of TIM and that patients with the combination of low-TIM/high-ZEB1 expression have a poorer outcome. In conclusion, our results as a whole suggest the engagement of an unedited TIM-ZEB1 axis in key pathological processes driving malignant phenotype acquisition in colorectal carcinogenesis. Thus, TIM-ZEB1 expression profiling could provide a robust prognostic biomarker in CRC patients, supporting targeted therapeutic strategies with better treatment selection and patients' outcomes

Consumption of healthy foods at different content of antioxidant vitamins and phytochemicals and metabolic risk factors for cardiovascular disease in men and women of the Moli-sani study.

BACKGROUND/OBJECTIVES:To categorize healthy food groups into categories of low-antioxidant (LAC) or high-antioxidant vitamins and phytochemicals content (HAC) and comparatively associate them with metabolic risk factors for cardiovascular disease (CVD). SUBJECTS/METHODS: A total of 6879 women (55±12 years) and 6892 men (56 ± 12 years) were analyzed from the Moli-sani cohort, randomly recruited from the general population. The European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary assessment. The antioxidant content of each food group was evaluated using Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione and United States Department of Agriculture (USDA) food composition tables. Healthy foods, according to a Mediterranean dietary pattern, were categorized into HAC or LAC; total food antioxidant content (FAC) score was constructed for a comparative evaluation of the consumption of these two groups. RESULTS: In men, an increase in FAC score, which represents an increased consumption of HAC with respect to LAC foods, was associated with a decrease in systolic blood pressure, diastolic blood pressure and C-reactive protein (CRP) (β=-0.5, P=0.02, β=-0.3, P=0.02 and β=-0.03, P=0.03, respectively). Logistic regression analyses showed that in men 15% (30 units) increase in FAC score was associated with 6% decrease in the likelihood of having hypertension (odds ratio (OR)=0.94, 95% confidence interval (CI) 0.91-0.98) and 3% decrease in the likelihood of having a high CRP risk level (OR=0.97, 95% CI 0.94-0.99). No significant associations were observed in women. CONCLUSIONS: A possible greater protective role of healthy HAC as compared with healthy LAC foods on hypertension and inflammation was detected in men. These results stress the importance of studying healthy foods according to their content in antioxidant vitamins and phytochemicals, in primary prevention of CVD