Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Hybrid Nanoscopy of Hybrid Nanomaterials

The combination of complementary techniques to characterize materials at the nanoscale is crucial to gain a more complete picture of their structure, a key step to design and fabricate new materials with improved properties and diverse functions. Here it is shown that correlative atomic force microscopy (AFM) and localization‐based super‐resolution microscopy is a useful tool that provides insight into the structure and emissive properties of fluorescent β‐lactoglobulin (βLG) amyloid‐like fibrils. These hybrid materials are made by functionalization of βLG with organic fluorophores and quantum dots, the latter being relevant for the production of 1D inorganic nanostructures templated by self‐assembling peptides. Simultaneous functionalization of βLG fibers by QD655 and QD525 allows for correlative AFM and two‐color super‐resolution fluorescence imaging of these hybrid materials. These experiments allow the combination of information about the topography and number of filaments that compose a fibril, as well as the emissive properties and nanoscale spatial distribution of the attached fluorophores. This study represents an important step forward in the characterization of multifunctionalized hybrid materials, a key challenge in nanoscience.     

A multi-granular linguistic model for management decision-making in performance appraisal

The performance appraisal is a relevant process to keep and improve the competitiveness of companies in nowadays. In spite of this relevance, the current performance appraisal models are not sufficiently well-defined either designed for the evaluation framework in which they are defined. This paper proposes a performance appraisal model where the assessments are modelled by means of linguistic information provided by different sets of reviewers in order to manage the uncertainty and subjectivity of such assessments. Therefore, the reviewers could express their assessments in different linguistic scales according to their knowledge about the evaluated employees, defining a multi-granular linguistic evaluation framework. Additionally, the proposed model will manage the multi-granular linguistic labels provided by appraisers in order to compute collective assessments about the employees that will be used by the management team to make the final decision about them.     

Technological Implications of Modifying the Extent of Cell Wall-Proanthocyanidin Interactions Using Enzymes

The transference and reactivity of proanthocyanidins is an important issue that affects the technological processing of some fruits, such as grapes and apples. These processes are affected by proanthocyanidins bound to cell wall polysaccharides, which are present in high concentrations during the processing of the fruits. Therefore, the effective extraction of proanthocyanidins from fruits to their juices or derived products will depend on the ability to manage these associations, and, in this respect, enzymes that degrade these polysaccharides could play an important role. The main objective of this work was to test the role of pure hydrolytic enzymes (polygalacturonase and cellulose) and a commercial enzyme containing these two activities on the extent of proanthocyanidin-cell wall interactions. The results showed that the modification promoted by enzymes reduced the amount of proanthocyanidins adsorbed to cell walls since they contributed to the degradation and release of the cell wall polysaccharides, which diffused into the model solution. Some of these released polysaccharides also presented some reactivity towards the proanthocyanidins present in a model solution.     

Grape seed removal: effect on phenolics,chromatic and organoleptic characteristics of red wine

Winemakers are interested in wines with low bitterness and astringency, and therefore, there is a preference for a higher presence of skin proanthocyanidins in wines. However, the information regarding the effect of reducing or eliminating seed proanthocyanidins from the must or fermenting wine on the characteristics of finished wines is scarce. For this reason, we elaborated a wine using Monastrell grapes from which the seeds had been removed and compared it with a control wine (CW) made from intact grapes. The anthocyanin and proanthocyanidin concentration and profile, and the chromatic and sensory characteristics were studied. The absence of seed proanthocyanidins did not affect anthocyanin concentration, although the proanthocyanidin concentration was 40% lower than in the CW. The copigmentation (CA) study showed that both wines had a similar extent of CA phenomena although colour intensity was higher when seed proanthocyanidins were present. The panellist evaluated the wines elaborated without seeds as being fruitier, less astringent and with an overall higher quality.     

In vitro digestibility of phenolic compounds from edible fruits: could it be explained by chemometrics?

The health benefits of phenolic compounds depend on the ingested amount, molecular diversity and gastrointestinal digestibility. The phenolic profile of eight fruits (blackberry, blueberry, strawberry, raspberry, mulberry, pomegranate, green and red globe grapes) was chemometrically associated with their in vitro digestibility (oral, gastric, intestinal). Extractable phenols, flavonoids and anthocyanins strongly correlated with each other (r ≥ 0.84), proanthocyanidins with anthocyanins (r = 0.62) and hydrolysable phenols with both extractable phenols (r = 0.45) and proanthocyanidins (r = ?0.54). Two principal components explained 93% of the variance [61% (free‐phenols), 32% (bounded‐phenols)], and four clusters were confirmed by hierarchical analysis, based in their phenolic richness (CLT 1‐4: low to high) and molecular diversity. In vitro digestibility of extractable phenols and flavonoids was blackberry (CLT‐4)> raspberry (CLT‐2)> red grape (CLT‐1) related to their phenolic richness (r ≥ 0.96; P < 0.001), but anthocyanins’ digestibility was pH‐dependent. Chemometrics is useful to predict the in vitro digestibility of phenolic compounds in the assayed fruits.     

Physical and nutritional properties of extruded products based on whole grain with the addition of wild legumes (Vicia lutea subsp. lutea var. hirta and Vicia sativa subsp. sativa)

Flour blends based on whole corn and rice with two added wild legumes at 15% level of cereal replacement were extruded to produce whole grain snacks. Extrusion temperature was 175 °C, and the moisture content was adjusted to 14%. The extruded products were evaluated for their physical, chemical and nutritional properties. Results showed that the addition of legumes produces a decrease in expansion in rice‐containing samples and an increase in solubility in corn‐containing samples. With only 15% of legume added to cereal, a significant increase in protein content and quality was obtained. An increase in fibre, polyphenol, iron and zinc content was also obtained. Protein digestibility was in the range of 81.8–85.3%. Mineral availability ranged from 6.4 to 16.3% for iron and 10–16.3% for zinc. The performance of each mixture during extrusion and the physical properties of the extruded products were considered to be similar to those expected for snack‐type products and described in the literature.