New derivatives of lupane triterpenoids disturb breast cancer mitochondria and induce cell death

Novel cationic dimethylaminopyridine derivatives of pentacyclic triterpenes were previously described to promote mitochondrial depolarization and cell death in breast and melanoma cell lines. The objective of this work was to further investigate in detail the mechanism of mitochondrial perturbations, correlating those effects with breast cancer cell responses to those same agents. Initially, a panel of tumor and non-tumor cell lines was grown in high-glucose or glucose-free glutamine-containing media, the later forcing cells to synthesize ATP by oxidative phosphorylation only. Cell proliferation, cell cycle, cell death and mitochondrial membrane polarization were evaluated. Inhibition of cell proliferation was observed, accompanied by an arrest in the G1-cell cycle phase, and importantly, by loss of mitochondrial membrane potential. On a later time-point, caspase-9 and 3 activation were observed, resulting in cell death. For the majority of test compounds, we determined that cell toxicity was augmented in the galactose media. To investigate direct evidences on mitochondria isolated rat liver mitochondria were used. The results showed that the compounds were strong inducers of the permeability transition pore. Confirming our previous results, this work shows that the novel DMAP derivatives strongly interact with mitochondria, resulting in pro-apoptotic signaling and cell death.     

Spectrum structures and biological functions of 8-mers in the human genome

The spectra of k-mer frequencies can reveal the structures and evolution of genome sequences. We confirmed that the trimodal spectrum of 8-mers in human genome sequences is distinguished only by CG2, CG1 and CG0 8-mer sets, containing 2,1 or 0 CpG, respectively. This phenomenon is called independent selection law. The three types of CG 8-mers were considered as different functional elements. We conjectured that (1) nucleosome binding motifs are mainly characterized by CG1 8-mers and (2) the core structural units of CpG island sequences are predominantly characterized by CG2 8-mers. To validate our conjectures, nucleosome occupied sequences and CGI sequences were extracted, then the sequence parameters were constructed through the information of the three CG 8-mer sets respectively. ROC analysis showed that CG1 8-mers are more preference in nucleosome occupied segments (AUC > 0.7) and CG2 8-mers are more preference in CGI sequences (AUC > 0.99). This validates our conjecture in principle.     

Distribution and function of prophage phiRv1 and phiRv2 among Mycobacterium tuberculosis complex

Mycobacterium tuberculosis complex (MTBC) is notorious for causing diseases, such as tuberculosis. Tuberculosis caused by M. tuberculosis remains a global public health concern. Two prophages, phiRv1 and phiRv2, can be found among most MTBC genomes. However, no precise functions have been assigned for the two prophages. In this paper, to find out the function of these two prophages, the distribution and function of phiRv1 and phiRv2 in MTBC genomes were analyzed from multiple omics data. We found that complex insertion, deletion, and reorganization appeared on the locus of two prophages in MTBC genomes; some genes of the two prophages can be translated and are functional from proteomic data; the expression of other prophage genes, such as Rv1577c, Rv2650c, Rv2652c, Rv2659c, and Rv2658c, can vary with environmental stresses and might enhance the fitness of MTBC. These data will facilitate our in-depth understanding of their function.     

A Model of Genome Size Dynamics During Speciation

A model developed for the evolving size of the repetitive part of the eukaryote genome during speciation was subjected to analytical and computer treatment. The basic assumption of the model was that two classes of repetitive DNA contribute mainly to macroevolutionary changes in genome size: arrays of tandem repeats (ATR) changing through unequal crossover and mobile genetic elements (MGE) changing presumably through an integration mechanism of the Tn- and Is-kind operating in bacteria. Within the framework of this model, the macroevolution of the MGE size is formally equivalent to that of the ATR in the particular case when shifts of chromatids have only one repeat out of register. This allowed us to consider genome size as a large set of various ATRs. The results obtained are as follows. If the duplication and deletion of repeats have unequal fixation probabilities during each speciation act, the predicted species distributions of genome size significantly deviate from the real ones; if they have equal fixation probabilities, there is a conformance between calculated and real distributions. In the latter case, the model reproduces the salient features of real distributions upon acceptance of 1) upper selective boundary nonspecifically limiting increase in genome size within the evolving taxonomic group and 2) non-neutrality of variability in genome size with respect to speciation.     

基因组数据揭示肺形侧耳X1野生菌株后代单孢的特异交配型位点

肺形侧耳味道鲜美,营养丰富,深受广大消费者喜爱。它属于四极性异宗结合担子菌,但其交配型位点结构仍未被解析。本研究利用二代测序技术对肺形侧耳的基因组进行测序,通过生物信息学方法找到了肺形侧耳野生菌株X1菌株后代单核菌株的交配型位点。结果显示肺形侧耳的A交配型位点较为特异,2株原生质体单核化菌株（X1-1和X1-15）的A交配型位点结构差异较大,X1-1含一对保守的HD1和HD2基因,而X1-15除了一对HD1和HD2基因外,还含有额外的2个HD2基因和1个HD1基因。肺形侧耳的B交配型位点与其他担子菌的交配型位点相似,含有8个信息素受体基因和1个信息素前体基因。本研究揭示的肺形侧耳特异的交配型位点结构为后期的遗传育种提供了理论依据。     

Genome editing in Bombyx mori: New opportunities for silkworm functional genomics and the sericulture industry

In recent years, research in life sciences has been remarkably revolutionized owing to the establishment, development and application of genome editing technologies. Genome editing has not only accelerated fundamental research but has also shown promising applications in agricultural breeding and therapy. In particular, the clustered, regularly interspaced, short palindromic repeat (CRISPR) technology has become an indispensable tool in molecular biology owing to its high efficacy and simplicity. Genome editing tools have also been established in silkworm (Bombyx mori), a model organism of Lepidoptera insects with high economic importance. This has remarkably improved the level and scope of silkworm research and could reveal new mechanisms or targets in basic entomology and pest management studies. In this review, we summarize the progress and potential of genome editing in silkworm and its applications in functional genomic studies for generating novel genetic materials.