Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.     

Nuclear DNA barcodes for cod identification in mildly-treated and processed food products

Gadoids are a group of fish with historical importance in the fishing industry. The high demand for cod is one of the reasons why cod products are often mislabelled, and numerous observations have been made on the replacement of Atlantic cod (Gadus morhua) by cheaper species or its illegal capture in contravention of fish quotas. Fish species identification is traditionally based on morphological features, but this may be difficult in case of heat-treated or processed products, or where the species look similar, as in the Gadoid group. DNA-based approaches (using either nuclear or mitochondrial DNA) are most commonly used in this case, due to their high specificity and to the high resilience of the target molecules to food processing techniques. In this article, we identified, using an automated screening approach, novel barcode regions and their associated primers in the nuclear genome, to be used for the efficient identification of Gadoids. The barcode regions were tested on official and commercial samples, raw or mildly treated products, like frozen, or salted, as well as pre-cooked complex mixtures and processed samples, using next-generation sequencing (NGS) technique. The method proposed could complement existing fish identification strategies in establishing an efficient framework to detect and prevent frauds along the food chain.     

Eye movements induced by lateral acceleration steps. Effect of visual context and acceleration levels

Different extracellular matrix (ECM) molecules, when presented to hippocampal neurons in culture in a substrate-bound form, exert strikingly similar effects on the establishment of neuronal polarity, i.e., the growth of axon-like major neurites is favored, whereas extension of dendrite-like minor neurites is inhibited. To gain insight into the underlying signal transduction processes, we have investigated the effects of modulators of protein kinase activity on the morphology of neurons cultured on tenascin-R, tenascin-C, and laminin-entactin substrates. We found differential effects of broad-spectrum protein kinase inhibitors: H-7 promoted the growth of minor neurites, whereas H-8 reduced the growth of major neurites on ECM but not control substrates. In contrast, chelerythrine, a specific inhibitor of protein kinase C, selectively affected growth of both minor and major neurites on control, but not on ECM substrates. Finally, reagents which elevate intracellular cAMP levels facilitated growth of minor neurites and inhibited growth of major neurites and thus interfered with the establishment of a polarized phenotype on both ECM and control substrates. Our results suggest that protein kinases mediate the effects of ECM molecules on neuronal polarity and that different kinases control extension of axons and dendrites.     

An Analytical Model to Measure the Effectiveness of Safety Management Systems: Global Safety Improve Risk Assessment (G-SIRA) Method

The ever-increasing complexity of production systems, together with the need to obtain efficient processes with limited costs, has led companies to develop custom tools for process control and management. Even for risk assessment, the traditional models often are overcome by methods that are best suited to specific needs. In this context, the aim of this paper was to propose a new model, which we call the global safety improve risk assessment (G-SIRA). This model can classify risks and identify corrective actions that allow the best risk reduction at the lowest cost. The proposed model, which is based on improvements to previous research, uses the analytic hierarchy process approach to develop a valid and simple tool for risk management. The G-SIRA method has been tested in a real-world application, i.e., it was applied to all of the processes of a textile company, and the results were compared with those obtained from the classical approach failure mode, effects, and criticality analysis. The comparison clearly showed the effectiveness of the proposed model.     

Effect of Glu-143 and His-231 substitutions on the catalytic activity and secretion of Bacillus subtilis neutral protease

On the basis of the homology with the Bacillus thermoproteolyticuszinc endopeptidase thermotysin, we hypothesized that Glu-143and His-231 are the key residues for the catalytic activityof the Bacillus subtilis neutral protease. To test this possibilityby site-directed mutagenesis, we substituted these two residueswith Ala, Ser, Trp and Arg, and Leu, Val and Cys respectively.All these substitutions dramatically affected the amount ofsecreted mutant proteins, as determined by immunological methods,and their catalytic activities. No appreciable secretion wasobserved with the three Glu mutants Trp, Ser and Arg, whereasthe Glu–Ala mutant enzyme was secreted at a level of afew hundred micrograms per litre of culture. The His mutantswere all secreted at higher levels (in the order of a few milligramsper litre) and their residual catalytic activity could be determinedusing Z-Ala-Leu-Ala as substrate. Our results confirm the keyrole played by Glu-143 and His-231 in catalysis and moreoversuggest the existence of a relationship between the catalyticactivity of the enzyme and the extent of its secretion. In thiscontext, we present data suggesting an autoproteolytic mechanismof cleavage of the precursor form of the enzyme, analogous tothe one previously reported for the B.subtilis subtilisin.     

Identification and analysis of isothiocyanates and new acylated anthocyanins in the juice of Raphanus sativus cv. Sango sprouts

The freeze-dried sprouts’ juice of Raphanus sativus (L.) cv. Sango was prepared and analysed for the first time. HPLC analysis of total isothiocyanates, after protein displacement, resulted in 77.8 ± 3.0 μmol/g of dry juice while GC–MS analysis of hexane and acetone extracts showed E- and Z-raphasatin (8.9 and 0.11 μmol/g, respectively) and sulforaphene (11.7 μmol/g), summing up to 20.7 ± 1.7 μmol/g of free isothiocyanates. Sprouts’ juice contained an unprecedented wealth of anthocyanins and a new fractionation methodology allowed us to isolate 34 mg/g of acylated anthocyanins (28.3 ± 1.9 μmol/g), belonging selectively to the cyanidin family. Analysis was performed by HPLC–PDA–ESI–MSⁿ and extended to deacylated anthocyanins and aglycones, obtained, respectively, by alkaline and acid hydrolysis. This study identified 70 anthocyanins, 19 of which have never been described before and 32 of which are reported here in R. sativus for the first time. Sango radish sprouts are exceptional dietary sources of heath-promoting micronutrients.     

A scaled 0.25-μm bipolar technology using full e-beamlithography

The full leverage offered by electron-beam lithography has been exploited in a scaled 0.25-μm double polysilicon bipolar technology. Devices and circuits were fabricated using e-beam lithography for all mask levels with level-to-level overlays tighter than 0.06 μm. Ion implantation was used to form a sub-100-nm intrinsic base profile, and a novel in-situ doped polysilicon emitter process was used to minimize narrow emitter effects. Transistors with 0.25-μm emitter width have current gains above 80 and cutoff frequencies as high as 40 GHz. A record ECL gate delay of 20.8 ps at 4.82 mW has been measured together with a minimum power-delay product of 47 fJ (42.1 ps at 1.12 mW). These results demonstrate the feasibility and resultant performance leverage of aggressive scaling of conventional bipolar technologies     

A comparison of fitting algorithms for diffusion-weighted MRI data analysis using an intravoxel incoherent motion model

Object

The objective of this study is to propose a modified VARiable PROjection (VARPRO) algorithm specifically tailored for fitting the intravoxel incoherent motion (IVIM) model to diffusion-weighted magnetic resonance imaging (DW-MRI) data from locally advanced rectal cancer (LARC).

Materials and methods

The proposed algorithm is compared with classical non-linear least squares (NLLS) analysis using the Levenberg-Marquardt (LM) algorithm and with two recently proposed algorithms for ‘segmented’ analysis. These latter two comprise two consecutive steps: first, a subset of parameters is estimated using a portion of data; second, the remaining parameters are estimated using the whole data and the previous estimates. The comparison between the algorithms was based on the \(R^2\) goodness-of-fit measure: performance analysis was carried out on real data obtained by DW-MRI on 40 LARC patients.

Results

The performance of the proposed algorithm was higher than that of LM in 64 % of cases; ‘segmented’ methods were poorer than our algorithm in 100 % of cases.

Conclusion

The proposed modified VARPRO algorithm can lead to better fit of the IVIM model to LARC DW-MRI data compared to other techniques.