Activiteit

At present, to the extent of our knowledge, there is no published life cycle assessment (LCA) evaluating the environmental impact of new bottom-up lithography versus conventional lithographic techniques. Quantification of this impact is central to verifying whether these new nanofabrication routes can replace conventional deposition techniques in industry as a more environmentally friendly option.Large-scale metabolomic studies have become common, and the reliability of the peak data produced by the various instruments is an important issue. However, less attention has been paid to the large number of uncharacterized peaks in untargeted metabolomics data. In this study, we tested various criteria to assess the reliability of 276 and 202 uncharacterized peaks that were detected in a gathered set of 30 plasma and urine quality control samples, respectively, using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). The linear relationship between the amounts of pooled samples and the corresponding peak areas was one of the criteria used to select reliable peaks. We used samples from approximately 3000 participants in the Tsuruoka Metabolome Cohort Study to investigate patterns of the areas of these uncharacterized peaks among the samples and clustered the peaks by combining the patterns and differences in the migration times. Our assessment pipeline removed substantial numbers of unreliable or redundant peaks and detected 35 and 74 reliable uncharacterized peaks in plasma and urine, respectively, some of which may correspond to metabolites involved in important physiological processes such as disease progression. We propose that our assessment pipeline can be used to help establish large-scale untargeted clinical metabolomic studies.The neurovascular unit (NVU) is a dynamic structure assembled by endothelial cells surrounded by a basement membrane, pericytes, astrocytes, microglia and neurons. A carefully coordinated interplay between these cellular and non-cellular components is required to maintain normal neuronal function, and in line with these observations, a growing body of evidence has linked NVU dysfunction to neurodegeneration. Plasminogen activators catalyze the conversion of the zymogen plasminogen into the two-chain protease plasmin, which in turn triggers a plethora of physiological events including wound healing, angiogenesis, cell migration and inflammation. The last four decades of research have revealed that the two mammalian plasminogen activators, tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), are pivotal regulators of NVU function during physiological and pathological conditions. Here, we will review the most relevant data on their expression and function in the NVU and their role in neurovascular and neurodegenerative disorders.Interactions involving Epstein-Barr virus (EBV) LMP2A and Nedd4 family E3 ubiquitin-protein ligases promote the ubiquitination of LMP2A-associated proteins, which results in the perturbation of normal B-cell signaling. Here, we solved the solution structure of the WW2 domain of hAIP4 and investigated the binding mode involving the N-terminal domain of LMP2A and the WW2 domain. The WW2 domain presented a conserved WW domain scaffold with a three-stranded anti-parallel β-sheet and bound two PY motifs via different binding mechanisms. Our NMR titration and ITC data demonstrated that the PY motifs of LMP2A can recognize and interact weakly with the XP groove of the WW2 domain (residues located around the third β-strand), and then residues between two PY motifs optimize the binding by interacting with the loop 1 region of the WW2 domain. In particular, the residue Val15 in the hairpin loop region between β1 and β2 of the WW2 domain exhibited unique changes depending on the terminal residues of the PY motif. This result suggested that the hairpin loop is responsible for additional interactions outside the XP groove, and this hypothesis was confirmed in a deuterium exchange experiment. These weak but wide interactions can stabilize the complex formed between the PY and WW domains.The isolation of high-quality RNA from endocrine pancreas sections represents a considerable challenge largely due to the high ribonuclease levels. Laser capture microdissection (LCM) of mammalian islets, in association with RNA extraction protocols, has emerged as a feasible approach to characterizing their genetic and proteomic profiles. However, a validated protocol to obtain high-quality RNA from LCM-derived human pancreas specimens that is appropriate for next-generation sequencing analysis is still lacking. In this study, we applied four methods (Picopure extraction kit, Qiazol protocol, Qiazol + Clean-up kit, and RNeasy Microkit + Carrier) to extract RNA from human islets obtained from both non-diabetic individuals and patients with type 2 diabetes who had undergone partial pancreatectomy, as well as handpicked islets from both non-diabetic and diabetic organ donors. The yield and purity of total RNA were determined by 260/280 absorbance using Nanodrop 100 and the RNA integrity number with a bioanalyzer. The results indicated that among the four methods, the RNeasy MicroKit + Carrier (Qiagen) provides the highest yield and purity.Ectonucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) has been described in human non-pathological endometrium in both epithelial and stromal components without changes along the cycle. read more It was identified as a stromal marker of basalis. In the present study, we aimed to evaluate NTPDase2 distribution, using immunolabeling and in situ enzyme activity approaches, in endometrial carcinoma (EC) at different tumor grades. NTPDase2 was present in tumor epithelial EC cells, as in the non-pathological endometria, but the expression underwent changes in subcellular distribution and also tended to decrease with the tumor grade. In stroma, NTPDase2 was identified exclusively at the tumor-myometrial junction but this expression was lost in tumors of invasive phenotype. We have also identified in EC samples the presence of the perivascular population of endometrial mesenchymal stem cells (eMSCs) positive for sushi domain containing 2 (SUSD2) and for NTPDase2, already described in non-tumoral endometrium. Our results point to NTPDase2 as a histopathological marker of tumor invasion in EC, with diagnostic relevance especially in cases of EC coexisting with other endometrial disorders, such as adenomyosis, which occasionally hampers the assessment of tumor invasion parameters.