125 research outputs found
Design and Synthesis of an E3 ligase Activity-Based Probe and its Application for the Discovery of a New Class of E3 Ligase
Information Acquisition and Decision-Making in Creditors\u27 Decision Environment.
This study identified the financial information used by the loan officers in a commercial lending context. The identification of information acquisition made it possible for the researcher to verify whether the manipulated financial information in the experiment was processed by the subjects. As a consequence, the inference concerning the impact of the treatment on loan officers\u27 decisions could be more conclusive. Most real decision tasks are similar to a situation in which the decision maker has to search for and decide which information to use rather than conforming to an a priori decision model specified by the researcher. The subjects in most lens model studies are, however, requested to perform tasks based on the cue sets predetermined by the researchers. Therefore, this study was also designed to investigate the impact of cue-selection discretion on loan officers\u27 decision-making. The impact of lessee accounting per SFAS 13 was used to operationalize this research methodology. According to the information acquisition of each subject, it was revealed that very few subjects processed the manipulated information disclosed in the footnotes. The MANOVA test revealed that neither the lessee accounting per SFAS 13 nor the time pressure affected loan officers\u27 decisions in terms of credit line and interest rate. The ANOVA test indicated that cue-selection discretion had a significant effect on loan officers\u27 lending decisions when the lessee company capitalized the leases. This study also investigated the impact of time pressure, experience level, and education level on the amount of information processed by the loan officers. The ANOVA results indicated that the incidence of the time pressure, the experience level in evaluating loan applications, and academic degree did not affect the amount of information retrieved by the loan officers
Effect of Different Combinations of Soybean and Wheat Bran on Enzyme Production from Aspergillus oryzae S
AbstractTo investigate the enzyme production from Aspergillus oryzae S. NPUST-FS-206-A1, different combinations of soybean and wheat bran (40%:60%, 50%:50%, and 60%:40% w/w) in koji were used as substrates in soybean koji fermentation. During cultivation period, pH change of various samples was similar. However, moisture content of koji obviously decreased. Koji with high content of soybean conducted high protease activity. After 48h of cultivation, koji containing 60% soybean showed the highest neutral protease activity of 84.38 U/g dry weight. Sample with high amount of wheat bran presented high amylase activity of 731.53 U/g dry weight. Reducing sugar content of koji was related to amylase activity. Moreover, different inoculum sizes of A. oryzae S. spore had no effect on the enzyme production
Polarity-specific high-level information propagation in neural networks
Analyzing the connectome of a nervous system provides valuable information about the functions of its subsystems. Although much has been learned about the architectures of neural networks in various organisms by applying analytical tools developed for general networks, two distinct and functionally important properties of neural networks are often overlooked. First, neural networks are endowed with polarity at the circuit level: Information enters a neural network at input neurons, propagates through interneurons, and leaves via output neurons. Second, many functions of nervous systems are implemented by signal propagation through high-level pathways involving multiple and often recurrent connections rather than by the shortest paths between nodes. In the present study, we analyzed two neural networks: the somatic nervous system of Caenorhabditis elegans (C. elegans) and the partial central complex network of Drosophila, in light of these properties. Specifically, we quantified high-level propagation in the vertical and horizontal directions: the former characterizes how signals propagate from specific input nodes to specific output nodes and the latter characterizes how a signal from a specific input node is shared by all output nodes. We found that the two neural networks are characterized by very efficient vertical and horizontal propagation. In comparison, classic small-world networks show a trade-off between vertical and horizontal propagation; increasing the rewiring probability improves the efficiency of horizontal propagation but worsens the efficiency of vertical propagation. Our result provides insights into how the complex functions of natural neural networks may arise from a design that allows them to efficiently transform and combine input signals
Structural basis for RING-Cys-Relay E3 ligase activity and its role in axon integrity.
MYCBP2 is a ubiquitin (Ub) E3 ligase (E3) that is essential for neurodevelopment and regulates axon maintenance. MYCBP2 transfers Ub to nonlysine substrates via a newly discovered RING-Cys-Relay (RCR) mechanism, where Ub is relayed from an upstream cysteine to a downstream substrate esterification site. The molecular bases for E2-E3 Ub transfer and Ub relay are unknown. Whether these activities are linked to the neural phenotypes is also unclear. We describe the crystal structure of a covalently trapped E2~Ub:MYCBP2 transfer intermediate revealing key structural rearrangements upon E2-E3 Ub transfer and Ub relay. Our data suggest that transfer to the dynamic upstream cysteine, whilst mitigating lysine activity, requires a closed-like E2~Ub conjugate with tempered reactivity, and Ub relay is facilitated by a helix-coil transition. Furthermore, neurodevelopmental defects and delayed injury-induced degeneration in RCR-defective knock-in mice suggest its requirement, and that of substrate esterification activity, for normal neural development and programmed axon degeneration
Plastic Optical Fiber Displacement Sensor Based on Dual Cycling Bending
In this study, a high sensitivity and easy fabricated plastic optical fiber (POF) displacement sensor is proposed. A POF specimen subjected to dual cyclic bending is used to improve the sensitivity of the POF displacement sensor. The effects of interval between rollers, relative displacement and number of rollers on the sensitivity of the displacement sensor are analyzed both experimentally and numerically. A good agreement between the experimental measurements and numerical calculations is obtained. The results show that the interval between rollers affects sensitivity most significantly than the other design parameters. Based on the experimental data, a linear equation is derived to estimate the relationship between the power loss and the relative displacement. The difference between the estimated results and the experimental results is found to be less than 8%. The results also show that the proposed POF displacement sensor based on dual cyclic bending can be used to detect displacement accurately
Adiponectin gene (ADIPOQ) polymorphisms correlate with the progression of nephropathy in Taiwanese male patients with type 2 diabetes
Aims: Polymorphisms of the ADIPOQ gene were associated with diabetic nephropathy (DN) in case-control studies predominantly among European populations. Gender may modify the ADIPOQ associated risk for DN. We investigated the association of 18 ADIPOQ polymorphisms with DN in a prospective Taiwanese cohort of type 2 diabetes (T2D) and explored whether gender plays a role in this genetic association. Methods: Selected single nucleotide polymorphisms (SNPs) of ADIPOQ were genotyped in 566 T2D patients with normoalbuminuria at baseline. DN was defined based on urinary albumin-to-creatinine ratio (ACR). The Cox proportional hazard model was used to explore the association of individual SNP to DN events under different genetic models over a 6-year follow-up period. Analyses were further stratified by gender. Results: In male patients, the adjusted hazard ratios under the recessive models were 1.81 for rs2241766 TT (vs. GT+GG, 95% CI=1.10-2.96, p=0.019) and 1.89 for rs1063537 CC (vs. CT+TT, 95% CI=1.15-3.11, p=0.013). In the Kaplan-Meier survival curve, males carrying rs2241766 TT (vs. GT+GG, p=0.050) and rs1063537 CC (vs. CT+TT, p=0.037) recessive homozygotes also had a reduced nephropathy-free survival rate. SNPs rs2241767 and rs2082940, both in strong correlation with tag SNP rs1063537 (r≥0.96), were also associated with DN progression in males. In females, ADIPOQ polymorphisms were not associated with the progression of DN. Conclusions: ADIPOQ genetic polymorphisms rs2241766 (+45T>G), rs1063537, rs2241767 and rs2082940 were correlated with the progression of DN in Taiwanese male patients with T2D. The role of gender in this ADIPOQ genetic association needs to be further investigated in other populations
Intramuscular electroporation with the pro-opiomelanocortin gene in rat adjuvant arthritis
Endogenous opioid peptides have an essential role in the intrinsic modulation and control of inflammatory pain, which could be therapeutically useful. In this study, we established a muscular electroporation method for the gene transfer of pro-opiomelanocortin (POMC) in vivo and investigated its effect on inflammatory pain in a rat model of rheumatoid arthritis. The gene encoding human POMC was inserted into a modified pCMV plasmid, and 0–200 μg of the plasmid-POMC DNA construct was transferred into the tibialis anterior muscle of rats treated with complete Freund's adjuvant (CFA) with or without POMC gene transfer by the electroporation method. The safety and efficiency of the gene transfer was assessed with the following parameters: thermal hyperalgesia, serum adrenocorticotropic hormone (ACTH) and endorphin levels, paw swelling and muscle endorphin levels at 1, 2 and 3 weeks after electroporation. Serum ACTH and endorphin levels of the group into which the gene encoding POMC had been transferred were increased to about 13–14-fold those of the normal control. These levels peaked 1 week after electroporation and significantly decreased 2 weeks after electroporation. Rats that had received the gene encoding POMC had less thermal hypersensitivity and paw swelling than the non-gene-transferred group at days 3, 5 and 7 after injection with CFA. Our promising results showed that transfer of the gene encoding POMC by electroporation is a new and effective method for its expression in vivo, and the analgesic effects of POMC cDNA with electroporation in a rat model of rheumatoid arthritis are reversed by naloxone
Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity
Ubiquitination is initiated by transfer of ubiquitin (Ub) from a ubiquitin-activating enzyme (E1) to a ubiquitin-conjugating enzyme (E2), producing a covalently linked intermediate (E2-Ub)(1). Ubiquitin ligases (E3s) of the 'really interesting new gene' (RING) class recruit E2-Ub via their RING domain and then mediate direct transfer of ubiquitin to substrates(2). By contrast, 'homologous to E6-AP carboxy terminus' (HECT) E3 ligases undergo a catalytic cysteine-dependent transthiolation reaction with E2-Ub, forming a covalent E3-Ub intermediate(3,4). Additionally, RING-between-RING (RBR) E3 ligases have a canonical RING domain that is linked to an ancillary domain. This ancillary domain contains a catalytic cysteine that enables a hybrid RING-HECT mechanism(5). Ubiquitination is typically considered a post-translational modification of lysine residues, as there are no known human E3 ligases with non-lysine activity. Here we perform activity-based protein profiling of HECT or RBR-like E3 ligases and identify the neuron-associated E3 ligase MYCBP2 (also known as PHR1) as the apparent single member of a class of RING-linked E3 ligase with esterification activity and intrinsic selectivity for threonine over serine. MYCBP2 contains two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates. Crystallographic characterization of this class of E3 ligase, which we designate RING-Cys-relay (RCR), provides insights into its mechanism and threonine selectivity. These findings implicate non-lysine ubiquitination in cellular regulation of higher eukaryotes and suggest that E3 enzymes have an unappreciated mechanistic diversity
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