FWAlgaeDB, an integrated genome database of freshwater algae

Algal genomics research contributes to a deeper understanding of algal evolution and provides useful genomics inferences correlated with various functions. Published algal genome sequences are very limited owing to genome assembly challenges. Because genome data of freshwater algae are rapidly increasing with the recent boom in next-generation sequencing and bioinformatics, an interface to store, interlink, and display these data is needed. To provide a substantial genomic resource specifically for freshwater algae, we developed the Freshwater Algae Database (FWAlgaeDB), a user-friendly, constantly updated online repository for integrating genomic data and annotation information. This database, which includes information on 204 freshwater algae, allows easy access to gene repertoires and gene clusters of interest and facilitates potential applications. Three functional modules are integrated into FWAlgaeDB: a Basic Local Alignment Search Tool tool for similarity analyses, a Search tool for rapid data retrieval, and a Download function for data downloads. This database tool is freely available at http://www.fwalagedb.com/#/home. To demonstrate the utility of FWAlgaeDB, we also individually mapped metagenomic sequencing reads of 10 water samples to FWAlgaeDB and Nt algae databases we constructed to obtain taxonomic composition information. According to the mapping results, FWAlgaeDB may be a better choice for identifying algal species in freshwater samples, with fewer potential false positives because of its focus on freshwater algal species. FWAlgaeDB can therefore serve as an open-access, sustained platform to provide genomic data and molecular analysis tools specifically for freshwater algae

Comprehensive Identification of Deleterious TP53 Missense VUS Variants Based on Their Impact on TP53 Structural Stability

TP53 plays critical roles in maintaining genome stability. Deleterious genetic variants damage the function of TP53, causing genome instability and increased cancer risk. Of the large quantity of genetic variants identified in TP53, however, many remain functionally unclassified as variants of unknown significance (VUS) due to the lack of evidence. This is reflected by the presence of 749 (42%) VUS of the 1785 germline variants collected in the ClinVar database. In this study, we addressed the deleteriousness of TP53 missense VUS. Utilizing the protein structure-based Ramachandran Plot-Molecular Dynamics Simulation (RPMDS) method that we developed, we measured the effects of missense VUS on TP53 structural stability. Of the 340 missense VUS tested, we observed deleterious evidence for 193 VUS, as reflected by the TP53 structural changes caused by the VUS-substituted residues. We compared the results from RPMDS with those from other in silico methods and observed higher specificity of RPMDS in classification of TP53 missense VUS than these methods. Data from our current study address a long-standing challenge in classifying the missense VUS in TP53, one of the most important tumor suppressor genes

Metabolomic and Transcriptomic Analyses of Lycium barbarum L. under Heat Stress

Heat stress has a strong and detrimental effect on plant growth and yield. Goji berry or wolfberry (Lycium barbarum L.) is a dual-purpose medicinal and food plant but an increase in high temperatures has caused a serious decline in wolfberry yield and quality. In this study, we first explored the heat stress responses of Goji berry, and found that heat stress adaptation mechanisms fluctuated over 48 h. Moreover, L.barbarum 1402 was more heat resistant while L.barbarum Ningqi No. 7 (N7) was sensitive to high temperatures, in which amino acids and alkaloids played key roles; expression and accumulation timing was also crucial. That is, 1402 responded to heat stress rapidly starting at 1 h under high temperature, activated related genes, and accumulated metabolites earlier in the amino acid metabolic pathway compared to N7, which responded to heat stress starting at 3 h under high temperature. Thus, 1402 resisted high temperatures much earlier and better compared to N7. Furthermore, joint transcriptome and metabolome analysis results showed that L-phenylalanine, L-tyrosine, N-benzylformamide, N-benzylmethylene isomethylamine, lysoPC 19:1, and N-acetyl-D-glucosamine-1-phosthate, as well as their related genes, were higher in content, or earlier in expression, in 1402 compared to N7 under heat treatment. This study initially elucidates that Goji berry 1402 has a better tolerance to heat stress than N7 for earlier and higher expression or accumulation of amino acids and alkaloids when related to high temperatures

Engineering and modification of microbial chassis for systems and synthetic biology

Engineering and modifying synthetic microbial chassis is one of the best ways not only to unravel the fundamental principles of life but also to enhance applications in the health, medicine, agricultural, veterinary, and food industries. The two primary strategies for constructing a microbial chassis are the top-down approach (genome reduction) and the bottom-up approach (genome synthesis). Research programs on this topic have been funded in several countries. The ‘Minimum genome factory’ (MGF) project was launched in 2001 in Japan with the goal of constructing microorganisms with smaller genomes for industrial use. One of the best examples of the results of this project is E. coli MGF-01, which has a reduced-genome size and exhibits better growth and higher threonine production characteristics than the parental strain [1]. The ‘cell factory’ project was carried out from 1998 to 2002 in the Fifth Framework Program of the EU (European Union), which tried to comprehensively understand microorganisms used in the application field. One of the outstanding results of this project was the elucidation of proteins secreted by Bacillus subtilis, which was summarized as the ‘secretome’ [2]. The GTL (Genomes to Life) program began in 2002 in the United States. In this program, researchers aimed to create artificial cells both in silico and in vitro, such as the successful design and synthesis of a minimal bacterial genome by John Craig Venter's group [3]. This review provides an update on recent advances in engineering, modification and application of synthetic microbial chassis, with particular emphasis on the value of learning about chassis as a way to better understand life and improve applications. Keywords: Microbial chassis, Systems biology, Synthetic biolog

Novel Gene Regulation in Normal and Abnormal Spermatogenesis

Spermatogenesis is a complex and dynamic process which is precisely controlledby genetic and epigenetic factors. With the development of new technologies (e.g., single-cell RNA sequencing), increasingly more regulatory genes related to spermatogenesis have been identified. In this review, we address the roles and mechanisms of novel genes in regulating the normal and abnormal spermatogenesis. Specifically, we discussed the functions and signaling pathways of key new genes in mediating the proliferation, differentiation, and apoptosis of rodent and human spermatogonial stem cells (SSCs), as well as in controlling the meiosis of spermatocytes and other germ cells. Additionally, we summarized the gene regulation in the abnormal testicular microenvironment or the niche by Sertoli cells, peritubular myoid cells, and Leydig cells. Finally, we pointed out the future directions for investigating the molecular mechanisms underlying human spermatogenesis. This review could offer novel insights into genetic regulation in the normal and abnormal spermatogenesis, and it provides new molecular targets for gene therapy of male infertility

Identification and characterization of the actinomycin G gene cluster in Streptomyces iakyrus

The gene cluster directing actinomycin G biosynthesis in Streptomyces iakyrus has been identified and sequenced. It contains one actinomycin synthetase I (ACMS I) gene and two copies of ACMS II and III genes. Genetic analysis demonstrates a unique partnership between the putative hydroxylation and chlorination activities as both acmG8 and acmG9 genes need to be transcribed for the biosynthesis of actinomycin G2–3, respectively