At the neural level, no significant micro- or macrostructural changes emerged in either group. Our findings suggest that working memory training in healthy older adults is associated with task-specific improvements, but these gains do not transfer to other cognitive domains, and it does not lead to structural brain changes. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.The formation of amyloid structures has traditionally been related to human neurodegenerative pathologies and, in recent years, the interest in these highly stable nanostructures was extended to biomaterial sciences. A common method to monitor amyloid growth is the analysis of Thioflavin T fluorescence. The use of this highly selective dye, diffused worldwide, allows mechanistic studies of supramolecular assemblies also giving back important insight on the structure of these aggregates. Here we present experimental evidence of self-quenching effect of Thioflavin T in presence of amyloid fibrils.  https://www.selleckchem.com/products/combretastatin-a4.html  A significant reduction of fluorescence lifetime of this dye which is not related to the properties of analyzed amyloid structures is found. This result is achieved by coupling Fluorescence Lifetime Imaging Microscopy with phasor approach as suitable model-free methods and constitute a serious warning that have to be taken in account if is dye is used for quantitative studies. © 2020 Wiley Periodicals, Inc.The incorporation of β-amino acids into a peptide sequence has gained particular attention as β- and α/β-peptides have shown remarkable proteolytic stability, even after a single homologation at the scissile bond. Several peptidases have been shown to cleave such bonds with high specificity but at a much slower rate compared to α-peptide bonds. In this study, a series of analogs of dipeptidyl peptidase-4 (DPP-4) substrate inhibitors were synthesized in order to investigate whether β-amino acid homologation at the scissile bond could be a valid approach to improving peptide stability towards DPP-4 degradation. DPP-4 cleaved the α/β-peptide bond after the N-terminal penultimate Pro with a broad specificity and retained full activity regardless of the β3 -amino acid side chain and peptide length. Significantly improved half-lives were observed for β3 Ile-containing peptides. Replacing the penultimate Pro with a conformationally constrained Pro mimetic led to proteolytic resistance. DPP-4 cleavage of α/β-peptide bonds with a broad promiscuity represents a new insight into the stability of peptide analogs containing β-amino acids as such analogs were thought to be stable towards enzymatic degradation. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Human caseinolytic protease component X and P (hClpXP) is a heterooligomeric ATP-dependent protease. The hClpX subunit catalyzes ATP hydrolysis whereas the hClpP subunit catalyzes peptide bond cleavage. In this study, we generated a peptidyl chloromethyl ketone (dansyl-FAPAL-CMK) that inhibited the hClpP subunit through alkylation of the catalytic His122, which was detected by LC-MS. This inhibitor is composed of a peptide sequence derived from a hydrolyzed peptide product of a substrate cleaved by hClpXP. Binding of FAPAL positions the electrophilic chloromethyl ketone moiety near His122 where alkylation occurs. Dansyl FAPAL-CMK exhibits selectivity for hClpXP over other ATP-dependent proteases such as hLon and the 26S proteasome and abolishes hClpXP activity in HeLa cell lysate. Using the fluorogenic peptide substrate FR-Cleptide as reporter, we detected biphasic inhibition time courses; this supports a slow-binding, time-dependent, covalent inhibition mechanism that is often found in active-site directed affinity labels. Because this inhibitor reacts only with hClpXP but not hLon or the proteasome, it has the potential to serve as a chemical tool to help validate endogenous protein substrates of hClpXP in cell lysate, thereby benefiting investigation of the physiological functions of hClpXP in different cell types or tissue samples. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.In 2017, the 8th edition of American Joint Committee on Cancer (AJCC) Staging Manual released the updating of TNM. The new edition introduces changes concerning tumor classification that could have a real innovative and useful clinical impact. The purpose of the study is to compare anatomic vs. prognostic stage group introduced in the new edition of AJCC staging system and its importance in clinical practice. We retrospectively analyzed the prognostic stage group introduced by the 8th edition of the AJCC staging system for breast cancer. We restaged a large series of patients with infiltrative breast cancer from 2004 to 2017 applying the AJCC 8th Edition prognostic stage group criteria. This study included 1575 patients with all molecular subtypes of breast cancer. Our follow-up included disease-free survival (DFS), disease-related survival (DRS), and overall survival (OS) data. Kaplan-Meier test was used for statistical analysis. The median follow-up was 7 years. The 5-year and 10-year OS were 96% and 90%, respectively. From our analysis, according to the 8th edition, the majority of patients included in the cohort had a down-staging to a better prognostic group except the triple-negative tumors. Most of the anatomic stage IIA turned into IA and IB. This new staging system seems to better relate to prognosis. Therefore, the prognostic stage represents an important support in breast cancer management since it could avoid unnecessary and ineffective therapies; in contrast, it could help realize the global evaluation of the risk of relapse/response to specific treatments, leading to a significant reduction in the national health cost. © 2020 Wiley Periodicals, Inc.PURPOSE To nondestructively evaluate the porosity of ten contemporary resin composite core materials using microtomographic (microCT) analysis. MATERIAL AND METHODS Resin composite core material samples (n = 12) including dual-cure, visible light cure only, and a self-cure material were fabricated using a standardized mold following manufacturer's recommendations. After storage in phosphate buffered saline for one week, specimens were analyzed using a microCT unit at 5.3-µm resolution over a rotational range of 360°. Image 3D recombination and analysis was accomplished using microCT software. Evaluated parameters included material volume investigated, closed pore number and volume, as well as closed pore percentage. Parameter mean values were evaluated with Kruskal-Wallis/Dunn at a 95% confidence level (α = 0.05). RESULTS Mean percent total porosity with standard deviation identified significant differences in decreasing order as Ti-Core 2.2 (0.4) > Ti-Core Auto E 1.3 (0.3) = Ti-Core Flow Plus 1.1 (0.02) > Clearfil Photo Core 0.