119 research outputs found
EXPLORING NEW REACTIVITIES OF ACTIVATED ISOCYANIDES TO ACCESS DIVERSE NITROGEN HETEROCYCLES
Ph.DDOCTOR OF PHILOSOPH
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Dissecting Distinct Roles of NEDDylation E1 Ligase Heterodimer APPBP1 and UBA3 Reveals Potential Evolution Process for Activation of Ubiquitin-related Pathways.
Despite the similar enzyme cascade in the Ubiquitin and Ubiquitin-like peptide(Ubl) conjugation, the involvement of single or heterodimer E1 activating enzyme has been a mystery. Here, by using a quantitative Förster Resonance Energy Transfer (FRET) technology, aided with Analysis of Electrostatic Similarities Of Proteins (AESOP) computational framework, we elucidate in detail the functional properties of each subunit of the E1 heterodimer activating-enzyme for NEDD8, UBA3 and APPBP1. In contrast to SUMO activation, which requires both subunits of its E1 heterodimer AOS1-Uba2 for its activation, NEDD8 activation requires only one of two E1 subunits, UBA3. The other subunit, APPBP1, only contributes by accelerating the activation reaction rate. This discovery implies that APPBP1 functions mainly as a scaffold protein to enhance molecular interactions and facilitate catalytic reaction. These findings for the first time reveal critical new mechanisms and a potential evolutionary pathway for Ubl activations. Furthermore, this quantitative FRET approach can be used for other general biochemical pathway analysis in a dynamic mode
Protein-Protein Affinity Determination by Quantitative FRET Quenching.
The molecular dissociation constant, Kd, is a well-established parameter to quantitate the affinity of protein-protein or other molecular interactions. Recently, we reported the theoretical basis and experimental procedure for Kd determination using a quantitative FRET method. Here we report a new development of Kd determination by measuring the reduction in donor fluorescence due to acceptor quenching in FRET. A new method of Kd determination was developed from the quantitative measurement of donor fluorescence quenching. The estimated Kd values of SUMO1-Ubc9 interaction based on this method are in good agreement with those determined by other technologies, including FRET acceptor emission. Thus, the acceptor-quenched approach can be used as a complement to the previously developed acceptor excitation method. The new methodology has more general applications regardless whether the acceptor is an excitable fluorophore or a quencher. Thus, these developments provide a complete methodology for protein or other molecule interaction affinity determinations in solution
PhaBOX: A web server for identifying and characterizing phage contigs in metagenomic data
Motivation: There is accumulating evidence showing the important roles of
bacteriophages (phages) in regulating the structure and functions of
microbiome. However, lacking an easy-to-use and integrated phage analysis
software hampers microbiome-related research from incorporating phages in the
analysis.
Results: In this work, we developed a web server, PhaBOX, to comprehensively
identify and analyze phage contigs in metagenomic data. To our best knowledge,
this is the first web server that supports integrated phage analysis, including
detecting phage contigs from the metagenomic assembly, lifestyle prediction,
taxonomic classification, and host prediction. Instead of treating the
algorithms as a black box, PhaBOX also supports visualization of the essential
features for making predictions. With the user-friendly graphical interface,
users with or without informatics training can easily use the web server for
analyzing phages in microbiome data.
Availability: The web server of PhaBOX is available via:
https://phage.ee.cityu.edu.hk. The source code of PhaBOX is available via:
https://github.com/KennthShang/PhaBOXComment: 5 pages, 1 figur
Effect of Yeast Fermentation on Volatile Flavor Substances and Nutritional Properties of Rice Bran
To investigate the effect of yeast fermentation on the flavor as well as nutritional properties of rice bran. In this study, volatile flavor substances of rice bran at different fermentation periods (0, 12, 18, 24 and 30 h) were identified by headspace solid-phase microextraction-gas chromatography-mass spectrometry, key volatile substances affecting the flavor of rice bran before and after fermentation were determined by orthogonal partial least squares analysis, and finally a comprehensive sensory evaluation of fermented rice bran was carried out and the changes of its nutritional composition by the optimal time of fermentation were compared. The results showed that the content and types of volatile substances of rice bran changed significantly during the fermentation process, the content of aldehydes in unfermented rice bran accounted for 35.99% and the content of alcohols accounted for 14.21%, and the content of aldehydes decreased to 5.52% and the content of alcohols increased to 60.87% at 30 h of fermentation. Among them, there were 15 key volatile substances. In the sensory evaluation, there was a significant (P<0.05, P<0.01) correlation between key volatile substances and rice bran aroma, and the sensory score of rice bran improved after fermentation, and the best sensory score was obtained for rice bran fermented for 18 h. Nonanal and ethyl nonanoate had the most significant (P<0.01) effects on the overall score of rice bran. In terms of nutritional composition, the protein content of yeast fermented rice bran flour was improved by 38.41% and the fiber content was improved by 18.21%. It indicated that yeast fermentation could not only effectively improve the flavor of rice bran, but also enhance the nutritional properties of rice bran flour as a food ingredient
Learning from real world data about combinatorial treatment selection for COVID-19
COVID-19 is an unprecedented global pandemic with a serious negative impact on virtually every part of the world. Although much progress has been made in preventing and treating the disease, much remains to be learned about how best to treat the disease while considering patient and disease characteristics. This paper reports a case study of combinatorial treatment selection for COVID-19 based on real-world data from a large hospital in Southern China. In this observational study, 417 confirmed COVID-19 patients were treated with various combinations of drugs and followed for four weeks after discharge (or until death). Treatment failure is defined as death during hospitalization or recurrence of COVID-19 within four weeks of discharge. Using a virtual multiple matching method to adjust for confounding, we estimate and compare the failure rates of different combinatorial treatments, both in the whole study population and in subpopulations defined by baseline characteristics. Our analysis reveals that treatment effects are substantial and heterogeneous, and that the optimal combinatorial treatment may depend on baseline age, systolic blood pressure, and c-reactive protein level. Using these three variables to stratify the study population leads to a stratified treatment strategy that involves several different combinations of drugs (for patients in different strata). Our findings are exploratory and require further validation
Efficient Thermal Conductance in Organometallic Perovskite CH3NH3PbI3 Films
Perovskite-based optoelectronic devices have shown great promise for solar
conversion and other optoelectronic applications, but their long-term
performance instability is regarded as a major obstacle to their widespread
deployment. Previous works have shown that the ultralow thermal conductivity
and inefficient heat spreading might put an intrinsic limit on the lifetime of
perovskite devices. Here, we report the observation of a remarkably efficient
thermal conductance, with conductivity of 11.2 +/- 0.8 W m^-1 K^-1 at room
temperature, in densely-packed perovskite CH3NH3PbI3 films, via noncontact
time-domain thermal reflectance measurements. The temperature-dependent
experiments suggest the important roles of organic cations and structural phase
transitions, which are further confirmed by temperature-dependent Raman
spectra. The thermal conductivity at room temperature observed here is over one
order of magnitude larger than that in the early report, suggesting that
perovskite device performance will not be limited by thermal stability
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