The Prp19p-associated complex in spliceosome activation

During spliceosome activation, a large structural rearrangement occurs that involves the release of two small nuclear RNAs, U1 and U4, and the addition of a protein complex associated with Prp19p. We show here that the Prp19p-associated complex is required for stable association of U5 and U6 with the spliceosome after U4 is dissociated. Ultraviolet crosslinking analysis revealed the existence of two modes of base pairing between U6 and the 5' splice site, as well as a switch of such base pairing from one to the other that required the Prp19p-associated complex during spliceosome activation. Moreover, a Prp19p-dependent structural change in U6 small nuclear ribonucleoprotein particles was detected that involves destabilization of Sm-like (Lsm) proteins to bring about interactions between the Lsm binding site of U6 and the intron sequence near the 5' splice site, indicating dynamic association of Lsm with U6 and a direct role of Lsm proteins in activation of the spliceosome.     

Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy

Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.     

Quantum coherent tunable coupling of superconducting qubits

To do large-scale quantum information processing, it is necessary to control the interactions between individual qubits while retaining quantum coherence. To this end, superconducting circuits allow for a high degree of flexibility. We report on the time-domain tunable coupling of optimally biased superconducting flux qubits. By modulating the nonlinear inductance of an additional coupling element, we parametrically induced a two-qubit transition that was otherwise forbidden. We observed an on/off coupling ratio of 19 and were able to demonstrate a simple quantum protocol.     

Analysis and construction of a quality prediction system for needle-punched non-woven fabrics

In this study, polyester and polypropylene staple fibers were selected as the raw material, and then processed through roller-carder, cross-lapper and needle-punching machine to produce needle-punched non-woven fabrics. First, the experiment was planned using the Taguchi method to select processing parameters that affect the quality of the needle-punched non-woven fabric to act as the control factors for this experiment. The quality characteristics were the longitudinal and transverse tensile strength of the non-woven fabric as well as longitudinal and transverse tear strength. The L₁₈ (2¹×3⁷) orthogonal array was selected for the experiment as it offered an improvement on the traditional method that wastes a lot of time, effort and cost. By using the analysis of variance (ANOVA) technique at the same time, the effect of significant factors on the production process of needle-punched non-woven fabrics could be determined. Finally, the processing parameters were set as the input parameters of a back-propagation neural network (BPNN). The BPNN consists of an input layer, a hidden layer and an output layer where the longitudinal/transverse tensile and tear strength of the non-woven fabric were set as the output parameters. This was used to construct a quality prediction system for needle-punched non-woven fabrics. The experimental results indicated that the prediction system implemented in this study provided accurate predictions.     

Optimization of the needle punching process for the nonwoven fabrics with multiple quality characteristics by grey-based taguchi method

This study is intended for finding out the optimal processing parameters for needle punching nonwoven fabrics in order to work out its maximal strength. Taguchi method together with grey relational analysis is employed to resolve the problem as regards multiple-quality optimization, and further discover the optimal combination of processing parameters for needle punching nonwoven fabrics. Firstly, orthogonal array L₁₈(2¹×3⁷) is used to deal with the processing parameters that may exert influence over the manufacturing of needle punching nonwoven fabrics. Then grey relational analysis is applied to resolve the deficiency of Taguchi method that focus on single quality characteristic. Next, the response table of grey relational analysis is used to obtain the optimal combination of processing parameters for multiple quality characteristics. In the current experiment quality characteristic refers to the tensile strength and tear strength of the nonwoven fabrics. Additionally, signal-to-noise ratio (SN ratio) calculation and analysis of variance (ANOVA) can be adopted to explore the experimental results. Through ANOVA, the significant factors that exert comparatively significant influence over the quality characteristic of the needle punching nonwoven fabrics, that is, the control factors are determined so that the quality characteristic of the needle punching nonwoven fabrics can be effectively controlled. Finally, confirmation experiment is conducted within 95 % confidence interval to verify the experimental reliability and reproducibility.     

Effects of alcohol-induced human peripheral blood mononuclear cell (PBMC) pretreated whey protein concentrate (WPC) on oxidative damage

Excessive alcohol consumption can induce apoptosis in a variety of tissues and influence the antioxidant status in peripheral blood mononuclear cells (PBMC). This paper investigates the effects of whey protein concentrate (WPC) pretreated in PBMC on the apoptosis and antioxidant status after the treatment of alcohol. The results show that the percentages of apoptotic cells in the alcohol-treated group were higher than those in the group without alcohol treatment. Additionally, there was higher glutathione (GSH) peroxidase (GPx) activity when the PBMC were treated with 300 mg/dL of alcohol. With regard to the activity of GSH reductase (GRx), there was higher activity in the group pretreated with WPC than in the group with the treatment of alcohol only. On the contrary, the levels of GSH were reduced after the treatment of alcohol, but there was a higher level of GSH in the group pretreated with WPC. In this study, it was found that the increased level of GSH in PBMC might not be attributed to the effect of GRx because there was still a higher level of GSH in the group with the treatment of WPC and BCNU (a GRx inhibitor) in this study. The results indicated that PBMC pretreated with WPC might ameliorate alcohol-induced effects such as imbalance of the antioxidant status.     

Improved subtilisin YaB production in Bacillus subtilis using engineered synthetic expression control sequences

Alkaline elastase YaB, a favorable meat tenderizer, is an extracellular subtilisin-type protease produced by wild strain alkalophilic Bacillus YaB. The gene ale coding for subtilisin YaB with its own expression control sequence has been cloned and expressed in Bacillus subtilis, but at levels much lower than in the parental strain Bacillus YaB. This study investigates the influence of various expression control sequences including expression control sequences of cdd and veg from B. subtilis, a synthetic expression control sequence (SECS), and engineered synthetic expression control sequences (engineered SECSs) on the expression of subtilisin YaB in B. subtilis. The engineered SECSs were generated by using the Polymerase Chain Reaction; their UP element, Shine-Dargarno (SD) sequence, or both were different from those of the native SECS. The expression efficiencies of SECS and engineered SECSs were higher than those of expression control sequences of ale, cdd, and veg. Substitution of the SD sequence of SECS resulted in higher expression of subtilisin YaB than substitution of the UP element, whereas combined substitution of both gave the highest expression. These results demonstrate that engineering of SECSs is an approach for improving subtilisin YaB production in B. subtilis. Moreover, it is suggested that these enginnered SECSs could potentially be used to express homologous and heterologous proteins in B. subtilis at high level.     

Development of probe-based ultraweak chemiluminescence technique for the detection of a panel of four oxygen-derived free radicals and their applications in the assessment of radical-scavenging abilities of extracts and purified compounds from food and herbal preparations

We report here the development of a probe-based ultraweak chemiluminescence (uwCL) method capable of detecting a panel of four oxygen-derived free radicals (ODFRs) including superoxide (O2-), hydrogen peroxide (H2O2), hydroxyl radical (*OH), and peroxyl radical (ROO*) using different probes specific for these radicals performed by the same uwCL analyzer. The selected radical-generating systems and their corresponding uwCL-probing emitters were validated. These ODFR-detecting systems were subsequently utilized by us to assess the radical-scavenging ability (RSA) of a variety of extracts and purified constituents derived from foods and herbal preparations. Our approach for assessing RSA for these constituents is based on the suppression of uwCL generated by each ODFR, and the degrees of inhibition have been shown to be dose-dependent. For this reason, the estimation of IC50 for each testing compound can be obtained from the curve constructed based on the percent of inhibitions of uwCL versus the concentrations of the compound tested. To illustrate the practical applications of our devised methodology, data for comparative studies of RSA activities of fermented extracts of Cordeceps sinensis, purified methylgallate isolated from Toona sinesis, resveratrol purified from grape seeds, plus epimedin C from the aerial part of the Epimedium plant (yinyanghuo) are to be presented.     

Seasonality and increasing frequency of Greenland glacial earthquakes

Some glaciers and ice streams periodically lurch forward with sufficient force to generate emissions of elastic waves that are recorded on seismometers worldwide. Such glacial earthquakes on Greenland show a strong seasonality as well as a doubling of their rate of occurrence over the past 5 years. These temporal patterns suggest a link to the hydrological cycle and are indicative of a dynamic glacial response to changing climate conditions.     

Cyclodepsipeptides: Isolation from Endophytic Fungi of Sarcophyton ehrenbergi and Verification of Their Larvicidal Activity via In-Vitro and In-Silico Studies

Culex pipiens mosquitoes are vectors to many viruses and can transmit diseases such as filariasis and avian malaria. The present study evaluated the larvicidal activity of marine-derived endophytic fungi Aspergillus nomius and Aspergillus flavus from the soft coral Sarcophyton ehrenbergi along with two known cyclodepsipeptide compounds, scopularide A (1) and B (2), isolated from A. flavus extract, against third-instar larvae of C. pipiens, using distilled water as a negative control and toosenedanin as a positive control. The structures of the isolated compounds were confirmed by various spectroscopic analyses. The lethal concentrations (LC₅₀ and LC₉₀) were calculated by probit analysis. Scopularide A was the most potent after 96 h treatment, with LC₅₀ and LC₉₀ values of 58.96 and 994.31 ppm, respectively, and with 82.66% mortality at a concentration of 300 ppm. To unravel the biochemical mechanism of the tested extracts and compounds, their effects against protease, chitinase, phenoloxidases and lipase enzymes from the whole-body tissue of C. pipiens were evaluated after 72 h treatment at LC₅₀ dose. Superior activity was observed for A. flavus extract against all tested enzymes. A molecular docking study was conducted for scopularide A and B on the four tested enzymes, to further verify the observed activity. Results revealed good binding affinities for both compounds as compared to the docked ligands, mainly via a number of hydrogen bonds. This was the first study to report the isolation of endophytic fungi A. flavus and A. nomius from the marine soft coral S. ehrenbergi. The endophytic fungal extract of A. flavus was found to be a promising source for a natural larvicidal agent against C. pipiens populations.