Abstract:DNA double-stranded break (DSB) is one of the most catastrophic damages of genotoxic insult. Inappropriate repair of DNA DSBs results in the loss of genetic information, mutation, and the generation of harmful genomic rearrangements, which predisposes an organism to immunodeficiency, neurological damage, and cancer. The tumor repressor p53 plays a key role in DNA damage response, and has been found to be mutated in 50% of human cancer. p53, p63, and p73 are three members of the p53 gene family. Recent discoveries have shown that human p53 gene encodes at least 12 isoforms. Different p53 members and isoforms play various roles in orchestrating DNA damage response to maintain genomic integrity. This review briefly explores the functions of p53 and its isoforms in DNA DSB repair.
Keywords:p53;p53 isoform;DNA double-stranded break repair;Cell death
Abstract:The stem/progenitor cell has long been regarded as a central cell type in development, homeostasis, and regeneration, largely owing to its robust self-renewal and multilineage differentiation abilities. The balance between self-renewal and stem/progenitor cell differentiation requires the coordinated regulation of cell cycle progression and cell fate determination. Extensive studies have demonstrated that cell cycle states determine cell fates, because cells in different cell cycle states are characterized by distinct molecular features and functional outputs. Recent advances in high-resolution epigenome profiling, single-cell transcriptomics, and cell cycle reporter systems have provided novel insights into the cell cycle regulation of cell fate determination. Here, we review recent advances in cell cycle-dependent cell fate determination and functional heterogeneity, and the application of cell cycle manipulation for cell fate conversion. These findings will provide insight into our understanding of cell cycle regulation of cell fate determination in this field, and may facilitate its potential application in translational medicine.
Abstract:Life may have begun in an RNA world, which is supported by increasing evidence of the vital role that RNAs perform in biological systems. In the human genome, most genes actually do not encode proteins; they are noncoding RNA genes. The largest class of noncoding genes is known as long noncoding RNAs (lncRNAs), which are transcripts greater in length than 200 nucleotides, but with no protein-coding capacity. While some lncRNAs have been demonstrated to be key regulators of gene expression and 3D genome organization, most lncRNAs are still uncharacterized. We thus propose several data mining and machine learning approaches for the functional annotation of human lncRNAs by leveraging the vast amount of data from genetic and genomic studies. Recent results from our studies and those of other groups indicate that genomic data mining can give insights into lncRNA functions and provide valuable information for experimental studies of candidate lncRNAs associated with human disease.
Keywords:Long noncoding RNA;Functional annotation;Genomic data mining;Machine learning
Abstract:Exosomes and long non-coding RNAs (lncRNAs) are emerging as important elements contributing to a more comprehensive understanding of cancer development and progression. The discovery of lncRNAs in exosomes further indicates their bona fide biological functional roles in cancer development and drug resistance. In this review, we describe the biogenesis of exosomes and summarize the function of exosomal lncRNAs in the field of cancer research. These findings strikingly advance current knowledge of exosomal lncRNAs and suggest that they may be promising diagnostic biomarkers and therapeutic targets for cancer.
Abstract:Proteins are dynamic, fluctuating between multiple conformational states. Protein dynamics, spanning orders of magnitude in time and space, allow proteins to perform specific functions. Moreover, under certain conditions, proteins can morph into a different set of conformations. Thus, a complete understanding of protein structural dynamics can provide mechanistic insights into protein function. Here, we review the latest developments in methods used to determine protein ensemble structures and to characterize protein dynamics. Techniques including X-ray crystallography, cryogenic electron microscopy, and small angle scattering can provide structural information on specific conformational states or on the averaged shape of the protein, whereas techniques including nuclear magnetic resonance, fluorescence resonance energy transfer (FRET), and chemical cross-linking coupled with mass spectrometry provide information on the fluctuation of the distances between protein domains, residues, and atoms for the multiple conformational states of the protein. In particular, FRET measurements at the single-molecule level allow rapid resolution of protein conformational states, where information is otherwise obscured in bulk measurements. Taken together, the different techniques complement each other and their integrated use can offer a clear picture of protein structure and dynamics.
Keywords:Conformational dynamics;Integrative structural biology;Distance restraint;Ensemble averaging;Nuclear magnetic resonance (NMR)
Abstract:Litchi (Litchi chinensis Sonn.) and longan (Dimocarpus longan Lour.) fruits have a succulent and white aril with a brown seed and are becoming popular worldwide. The two fruits have been used in traditional Chinese medicine as popular herbs in the treatment of neural pain, swelling, and cardiovascular disease. The pericarp and seed portions as the by-products of litchi and longan fruits are estimated to be approximately 30% of the dry weight of the whole fruit and are rich in bioactive constituents. In the recent years, many biological activities, such as tyrosinase inhibitory, antioxidant, anti-inflammatory, immunomodulatory, anti-glycated, and anti-cancer activities, as well as memory-increasing effects, have been reported for the litchi and longan pericarp and seed extracts, indicating a potentially significant contribution to human health. With the increasing production of litchi and longan fruits, enhanced utilization of the two fruit by-products for their inherent bioactive constituents in relation to pharmacological effects is urgently needed. This paper reviews the current advances in the extraction, processing, identification, and biological and pharmacological activities of constituents from litchi and longan by-products. Potential utilization of litchi and longan pericarps and seeds in relation to further research is also discussed.
Abstract:Aluminum (Al) is the most abundant metal element in the earth’s crust. On acid soils, at pH 5.5 or lower, part of insoluble Al-containing minerals become solubilized into soil solution, with resultant highly toxic effects on plant growth and development. Nevertheless, some plants have developed Al-tolerance mechanisms that enable them to counteract this Al toxicity. One such well-documented mechanism is the Al-induced secretion of organic acid anions, including citrate, malate, and oxalate, from plant roots. Once secreted, these anions chelate external Al ions, thus protecting the secreting plant from Al toxicity. Genes encoding the citrate and malate transporters responsible for secretion have been identified and characterized, and accumulating evidence indicates that regulation of the expression of these transporter genes is critical for plant Al tolerance. In this review, we outline the recent history of research into plant Al-tolerance mechanisms, with special emphasis on the physiology of Al-induced secretion of organic acid anions from plant roots. In particular, we summarize the identification of genes encoding organic acid transporters and review current understanding of genes regulating organic acid secretion. We also discuss the possible signaling pathways regulating the expression of organic acid transporter genes.
Abstract:Anthraquinone dyes, which contain anthraquinone chromophore groups, are the second largest class of dyes after azo dyes and are used extensively in textile industries. The majority of these dyes are resistant to degradation because of their complex and stable structures; consequently, a large number of anthraquinone dyes find their way into the environment causing serious pollution. At present, the microbiological approach to treating printing and dyeing wastewater is considered to be an economical and feasible method, and reports regarding the bacterial degradation of anthraquinone dyes are increasing. This paper reviews the classification and structures of anthraquinone dyes, summarizes the types of degradative bacteria, and explores the possible mechanisms and influencing factors of bacterial anthraquinone dye degradation. Present research progress and existing problems are further discussed. Finally, future research directions and key points are presented.