Mitochondrial EF4 links respiratory dysfunction and cytoplasmic translation in Caenorhabditis elegans

AbstractHow animals coordinate cellular bioenergetics in response to stress conditions is an essential question related to aging, obesity and cancer. Elongation factor 4 (EF4/LEPA) is a highly conserved protein that promotes protein synthesis under stress conditions, whereas its function in metazoans remains unknown. Here, we show that, in Caenorhabditis elegans, the mitochondria-localized CeEF4 (referred to as mtEF4) affects mitochondrial functions, especially at low temperature (15°C). At worms' optimum growing temperature (20°C), mtef4 deletion leads to self-brood size reduction, growth delay and mitochondrial dysfunction. Transcriptomic analyses show that mtef4 deletion induces retrograde pathways, including mitochondrial biogenesis and cytoplasmic translation reorganization. At low temperature (15°C), mtef4 deletion reduces mitochondrial translation and disrupts the assembly of respiratory chain supercomplexes containing complex IV. These observations are indicative of the important roles of mtEF4 in mitochondrial functions and adaptation to stressful conditions

Research on the Experimental Teaching Method of Vibration Damping Fastener for Undergraduates Majoring in Rail Transit

Experiment is an important teaching link in talent training. Aiming at the current situation and problems of the experimental teaching of rail transit major, taking the experimental teaching of vibration damping fastener drop weight for railway engineering major of Central South University as an example, the specific methods of the new experimental teaching mode for undergraduates majoring in rail transit are expounded: Improve the subject experimental system, build an open experimental platform, and improve the school-enterprise resource sharing system, etc. This model is conducive to the reform and development of the experimental teaching model for rail transit majors and related science and engineering majors

Rational Design of an Epitope-Based Hepatitis C Virus Vaccine

Despite improving treatment methods and therapeutic options, hepatitis C virus (HCV) remains a major global disease burden, and a vaccine would help greatly in reducing its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response, thus a vaccine must elicit an immune response toward conserved, functionally important epitopes. Using structural data of the broadly neutralizing antibody HCV1 in complex with a conserved linear epitope from the HCV E2 protein (aa 412-423, referred to as epitope I or domain E), we performed structure-based design to generate vaccine immunogens to induce antibody responses to this epitope. Designs selected for immunological characterization included a stabilized minimal epitope structure based on a defensin protein, as well as a bivalent vaccine featuring two copies of epitope I on the E2 surface. In vivo studies confirmed that these designs successfully generated robust antibody responses to this epitope, and sera from vaccinated mice neutralized HCV. In addition to presenting several effective HCV vaccine immunogens, this study demonstrates that induction of neutralizing anti-HCV antibodies is possible using an epitope-based vaccine, providing the basis for further efforts in structure-based vaccine design to target this and other critical epitopes of HCV

Research on Practical Teaching of Railway Engineering Specialty Based on Temperature Test of Rubber Sleepers

Experimental teaching plays an important role in cultivating college students' innovative ability. This paper takes the practical teaching of the temperature test of the new rubber sleeper as an example to analyze the current situation and problems of the practical teaching of railway engineering. The specific measures of the new system of practical teaching of railway engineering are put forward: Build a practical teaching curriculum system, improve the practical teaching evaluation mechanism, and promote the sharing of school-enterprise resources, so as to cultivate outstanding railway engineering talents with engineering ability and innovative spirit

Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole

Graphene Oxide Quantum Dots Covalently Functionalized PVDF Membrane with Significantly-Enhanced Bactericidal and Antibiofouling Performances

Covalent bonding of graphene oxide quantum dots (GOQDs) onto amino modified polyvinylidene fluoride (PVDF) membrane has generated a new type of nano-carbon functionalized membrane with significantly enhanced antibacterial and antibiofouling properties. A continuous filtration test using E. coli containing feedwater shows that the relative flux drop over GOQDs modified PVDF is 23%, which is significantly lower than those over pristine PVDF (86%) and GO-sheet modified PVDF (62%) after 10 h of filtration. The presence of GOQD coating layer effectively inactivates E. coli and S. aureus cells, and prevents the biofilm formation on the membrane surface, producing excellent antimicrobial activity and potentially antibiofouling capability, more superior than those of previously reported two-dimensional GO sheets and one-dimensional CNTs modified membranes. The distinctive antimicrobial and antibiofouling performances could be attributed to the unique structure and uniform dispersion of GOQDs, enabling the exposure of a larger fraction of active edges and facilitating the formation of oxidation stress. Furthermore, GOQDs modified membrane possesses satisfying long-term stability and durability due to the strong covalent interaction between PVDF and GOQDs. This study opens up a new synthetic avenue in the fabrication of efficient surface-functionalized polymer membranes for potential waste water treatment and biomolecules separation

Network traffic characteristics of hyperscale data centers in the era of cloud applications

We present the network architecture of Alibaba Cloud DCs and investigate their traffic characteristics based on statistical data and captured traces. The statistical coarse-grained data are in the granularity of one minute, while the captured traces are fine-grained data that are in the granularity of one packet. We study the traffic features from the perspective of a macroscopic view, network performance, and microscopic view. The results report that the average utilization ratio of spine switches is stable when the observation time period reaches one day and the intra-ToR traffic ratio is in the range of 2%-10%. By mapping the folded-Clos topology to a tree topology and considering logical switching planes, we obtain the traffic matrix among pods from the average port utilization ratio. As we further investigate the perspective of network performance and the microscopic view, we find that there is no cell loss happening as the normalized queue speed Q_s is lower than 0.4. The normalized queue speed Q_s is defined as the total bytes of a queue sent in 1 s divided by 100 Gb, which reflects the packet sending speed of the queue. The observed maximum buffer size for one port conforms with the calculated maximum buffer occupation of 2.8 MB. By analyzing the captured traces, we find that the packet length is subject to a trimodal distribution. Under a time granularity of 10 ms, the instant bandwidth of one ToR port could reach 96 Gb/s at an average load of around 0.2 under a maximum link bandwidth of 100 Gb/s.</p

Comprehensive identification of alternative back-splicing in human tissue transcriptomes

Circular RNAs (circRNAs) are covalently closed RNAs derived from back-splicing of genes across eukaryotes. Through alternative back-splicing (ABS), a single gene produces multiple circRNAs sharing the same back-splice site. Although many ABS events have recently been discovered, to what extent ABS involves in circRNA biogenesis and how it is regulated in different human tissues still remain elusive. Here, we reported an in-depth analysis of ABS events in 90 human tissue transcriptomes. We observed that ABS occurred for about 84% circRNAs. Interestingly, alternative 5\u27 back-splicing occurs more prevalently than alternative 3\u27 back-splicing, and both of them are tissue-specific, especially enriched in brain tissues. In addition, the patterns of ABS events in different brain regions are similar to each other and are more complex than the patterns in non-brain tissues. Finally, the intron length and abundance of Alu elements positively correlated with ABS event complexity, and the predominant circRNAs had longer flanking introns and more Alu elements than other circRNAs in the same ABS event. Together, our results represent a resource for circRNA research-we expanded the repertoire of ABS events of circRNAs in human tissue transcriptomes and provided insights into the complexity of circRNA biogenesis, expression, and regulation