Global identification of substrates for PTMs (post-translational modifications) represents a critical but yet dauntingly challenging task in understanding biology and disease pathology. Here we presented a synthetic biology approach, namely 'YESS', which coupled Y2H (yeast two hybrid) interactome screening with PTMs reactions reconstituted in bacteria for substrates identification and validation, followed by the functional validation in mammalian cells. Specifically, the sequence-independent Gateway® cloning technique was adopted to afford simultaneous transfer of multiple hit ORFs (open reading frames) between the YESS sub-systems. In proof-of-evidence applications of YESS, novel substrates were identified for UBE3A and UFL1, the E3 ligases for ubiquitination and ufmylation, respectively. Therefore, the YESS approach could serve as a potentially powerful tool to study cellular signaling mediated by different PTMs.We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer's disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magnetic resonance imaging (MRI) scans showed diffuse atrophy in the fronto-parietal regions. In addition, 18F-fludeoxyglucose positron emission tomography (FDG-PET) showed reduced tracer uptake in the parietal and temporal cortices, bilaterally. The second patient developed memory dysfunction at the age of 49, and his mother was also affected. Amyloid positron emission tomography (PET) was positive, but MRI scans did not reveal any atrophy. Targeted NGS and Sanger sequencing identified a heterozygous C to T exchange in PSEN1 exon 5 (c.356C>T), resulting in a p.Thr119Ile mutation. The mutation is located in the conserved HL-I loop, where several Alzheimer's disease (AD) related mutations have been described. Structure analyses suggested that Thr119Ile mutation may result in a significant change inside conservative loop. Additional in vitro studies are needed to estimate the role of the PSEN1 Thr119Ile in AD disease progression.The hemp flea beetle Psylliodes attenuata (Coleoptera Chrysomelidae Psylliodes) is a common pest of Cannabis sativa, including cultivars of both industrial hemp and medicinal marijuana. Both the larval and adult stages of this beetle can cause significant damages to C. sativa, resulting in substantial crop losses. At present, little is known about the populations of this pest, including its genetic diversity. In this study, we obtained 281 P. attenuata samples from nine field sites representing broad industrial hemp productions in China and analyzed their DNA sequences at the mitochondrial COI gene, the insect DNA barcode. Our analyses revealed a total of 48 haplotypes, with 28 being found only in one specimen each while the remaining 20 were shared by two or more specimens each.  https://www.selleckchem.com/products/bb-94.html  Of the 20 shared haplotypes, eight were shared among local populations often from far away locations, consistent with recent long-distance dispersals. However, the observed putative long-distance dispersals have not obscured the significant genetic differentiations among the regional populations from northeastern, eastern, central and southwestern China. Interestingly, haplotype network analyses suggest evidence for potential mitochondrial recombination in natural populations of this species. We briefly discuss the implications of our results on its evolution, center of diversity, route of spread, and pest management strategies in hemp fields.There are many methods widely applied in the engineering of biomaterials to improve the mechanical properties of the dental composites. The aim of this study was to assess the effect of modification of dental composites with liquid rubber on their mechanical properties, degree of conversion, viscosity, and cytotoxicity. Both flow and packable composite consisted of a mixture of Bis-GMA, TEGDMA, UDMA, and EBADMA resins reinforced with 60 and 78 wt.% ceramic filler, respectively. It was demonstrated that liquid rubber addition significantly increased the fracture toughness by 9% for flow type and 8% for condensable composite. The influence of liquid rubber on flexural strength was not statistically significant. The addition of the toughening agent significantly reduced Young's modulus by 7% and 9%, respectively, while increasing deformation at breakage. Scanning electron microscopy (SEM) observations allowed to determine the mechanisms of toughening the composites reinforced with ceramic particles. These mechanisms included bridging the crack edges, blocking the crack tip by particles and dissipation of fracture energy by deflection of the cracks on larger particles. The degree of conversion increased after modification, mainly due to a decrease in the matrix resin viscosity. It was also shown that all dental materials were nontoxic according to ISO 10993-5, indicating that modified materials have great potential for commercialization and clinical applications.Background Stroke causes a wide variety of clinical manifestations that may have a negative impact on quality of life. Therefore, it is very important to use specific instruments for measuring quality of life in individuals who suffered a stroke. The aim of this study was to develop a psychometrically validated Spanish version of the Newcastle stroke-specific quality of life measure (NEWSQOL). Methods A psychometric validation of the Spanish version of the NEWSQOL questionnaire was carried out in 159 patients. The reliability (intraclass correlation coefficient and Cronbach's alpha coefficient), validity (factorial analysis and Spearman's coefficient), feasibility (response rate), and the ceiling and floor effects were calculated. Results Internal consistency showed that Cronbach's alpha coefficient was 0.93. The test-retest reliability was high or excellent for all domains (range 0.71-0.97 p less then 0.001). The response rate of the questionnaire was 100% and the average administration time was 20.5 (±7.2) min. No ceiling effect was detected and two domains (pain and vision) may have a significant potential for floor effect. Construct validity showed that all the variables are important enough to keep them all in the questionnaire. Concerning convergent construct validity, a high correlation was found with the Nottingham Health Profile, the Barthel Index, and the Modified Rankin Scale. Conclusion The Spanish version of the NEWSQOL questionnaire is reliable, valid, and feasible to evaluate quality of life in the Spanish population.