Common carp (Cyprinus carpio) is an allotetraploid species derived from recent whole genome duplication and provides a model to study polyploid genome evolution in vertebrates. Here, we generate ...three chromosome-level reference genomes of C. carpio and compare to related diploid Cyprinid genomes. We identify a Barbinae lineage as potential diploid progenitor of C. carpio and then divide the allotetraploid genome into two subgenomes marked by a distinct genome similarity to the diploid progenitor. We estimate that the two diploid progenitors diverged around 23 Mya and merged around 12.4 Mya based on the divergence rates of homoeologous genes and transposable elements in two subgenomes. No extensive gene losses are observed in either subgenome. Instead, we find gene expression bias across surveyed tissues such that subgenome B is more dominant in homoeologous expression. CG methylation in promoter regions may play an important role in altering gene expression in allotetraploid C. carpio.
Clostridioides difficile is one of the most common causes of antibiotic-associated diarrhea in developed countries. As key virulence factors of C. difficile, toxin A (TcdA) and toxin B (TcdB) act by ...glucosylating and inactivating Rho and Ras family small GTPases in host cells, which leads to actin cytoskeleton disruption, cell rounding, and ultimately cell death. Here we present the co-crystal structure of the glucosyltransferase domain (GTD) of TcdA in complex with its substrate human RhoA at 2.60-angstrom resolution. This structure reveals that TcdA GTD grips RhoA mainly through its switch I and switch II regions, which is complemented by interactions involving RhoA's pre-switch I region. Comprehensive structural comparisons between the TcdA GTD-RhoA complex and the structures of TcdB GTD in complex with Cdc42 and R-Ras reveal both the conserved and divergent features of these two toxins in terms of substrate recognition. Taken together, these findings establish the structural basis for TcdA recognition of small GTPases and advance our understanding of the substrates selectivity of large clostridial toxins.
Teachers' job happiness in private universities is an important element for the healthy and orderly development of universities and an inevitable requirement for the construction of university ...faculty, and it has become a hot topic of research in the field of private higher education at present. However, there is still a lack of empirical studies on the factors influencing job happiness in private universities. This study constructs a theoretical model between professional identity, job competence, professional motivation, professional prospects, perceived fairness, job achievements and job happiness, and explores the specific drivers of teachers' job happiness in private universities based on empirical research. The results of the data analysis showed that professional identity, job competence, professional prospects, perceived fairness, job achievements, and professional motivation all had significant effects on teachers' job happiness, and the effects were decreasing. This study examined the effects of job happiness in practice in private universities, which helped private universities to enhance teachers' professional identity, strengthen organizational support for teacher development, promote teachers' teaching ability, improve job competence, and build a developmental teacher evaluation mechanism.
Toxin A (TcdA) and toxin B (TcdB) are two key virulence factors secreted by
, which is listed as an urgent threat by the CDC. These two large homologous exotoxins are mainly responsible for diseases ...associated with
infection (CDI) with symptoms ranging from diarrhea to life threatening pseudomembranous colitis. Single-domain camelid antibodies (VHHs) AH3 and AA6 are two potent antitoxins against TcdA, which when combined with two TcdB-targeting VHHs showed effective protection against both primary and recurrent CDI in animal models. Here, we report the co-crystal structures of AH3 and AA6 when they form complexes with the glucosyltransferase domain (GTD) and a fragment of the delivery and receptor-binding domain (DRBD) of TcdA, respectively. Based on these structures, we find that AH3 binding enhances the overall stability of the GTD and interferes with its unfolding at acidic pH, and AA6 may inhibit the pH-dependent conformational changes in the DRBD that is necessary for pore formation of TcdA. These studies reveal two functionally critical epitopes on TcdA and shed new insights into neutralizing mechanisms and potential development of epitope-focused vaccines against TcdA.
A highly efficient one‐pot synthesis of polysubstituted pyridine has been achieved through copper‐catalyzed oxidative sp3 C−H coupling of acetophenones with toluene derivatives. Besides, the ...polysubstituted benzene was obtained through copper‐catalyzed coupling of acetophenones. Both of the reactions exhibited a good functional group tolerance to produce a 2,4,6‐triphenylpyridine or 1,3,5‐triarylbenzene in high yields. Compared with previous methods, these transformations allow a highly flexible and efficient preparation of substituted pyridines and benzenes.
Clostridium difficile is an opportunistic pathogen that establishes in the colon when the gut microbiota are disrupted by antibiotics or disease. C. difficile infection (CDI) is largely caused by two ...virulence factors, TcdA and TcdB. Here, we report a 3.87-Å-resolution crystal structure of TcdB holotoxin that captures a unique conformation of TcdB at endosomal pH. Complementary biophysical studies suggest that the C-terminal combined repetitive oligopeptides (CROPs) domain of TcdB is dynamic and can sample open and closed conformations that may facilitate modulation of TcdB activity in response to environmental and cellular cues during intoxication. Furthermore, we report three crystal structures of TcdB-antibody complexes that reveal how antibodies could specifically inhibit the activities of individual TcdB domains. Our studies provide novel insight into the structure and function of TcdB holotoxin and identify intrinsic vulnerabilities that could be exploited to develop new therapeutics and vaccines for the treatment of CDI.
An efficient one-pot three-component stepwise approach for the synthesis of N-2-aryl-substituted-1,2,3-triazoles has been developed. By using this azide-chalcone oxidative cycloaddition and ...post-triazole arylation, a series of N-2-aryl-substituted-1,2,3-triazoles are readily prepared under mild conditions in excellent yields and high regioselectivity. Both the catalyst and substrates are readily available.
We have developed a one-pot, ring-opening/ring-closure, Rh(III)-catalysed, C–H functionalization of phenyloxazoles with diazo compounds to produce isocoumarins and isoquinolinones. It is a green ...environmentally friendly reaction pathway.
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Acid-controlled, chemodivergent and redox-neutral annulations for the synthesis of isocoumarins and isoquinolinones have been realized via Rh(III)-catalyzed CH activation. Diazo compounds act as a carbene precursor, and coupling occurs in one-pot process, where adipic acid and trimethylacetic acid promote chemodivergent cyclizations.
Charcoal impregnated with zinc was able to catalyze the cycloaddition of organic azides and alkynes to provide the corresponding 1,4‐disubstituted 1,2,3‐triazoles and 1,4,5‐trisubstituted ...1,2,3‐triazoles in good to excellent yields. Noteworthy was that the novel and heterogeneous catalyst was successfully applied in this cycloaddition reaction for the first time and could also be easily recycled.
1,4‐Disubstituted 1,2,3‐triazoles and 1,4,5‐trisubstituted 1,2,3‐triazoles were easily obtained by a novel Zn/C‐catalyzed 3+2cycloaddition between organic azides and alkynes.
In pursuit of high imaging quality, optical sparse aperture systems must correct piston errors quickly within a small range. In this paper, we modified the existing deep-learning piston detection ...method for the Golay-6 array, by using a more powerful single convolutional neural network based on ResNet-34 for feature extraction; another fully connected layer was added, on the basis of this network, to obtain the best results. The Double-defocused Sharpness Metric (DSM) was selected first, as a feature vector to enhance the model performance; the average RMSE of the five sub-apertures for valid detection in our study was only 0.015λ (9 nm). This modified method has higher detecting precision, and requires fewer training datasets with less training time. Compared to the conventional approach, this technique is more suitable for the piston sensing of complex configurations.
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