A biotin-guided near-infrared fluorescent probe for imaging hydrogen sulfide and differentiating cancer cells.

Imaging cancer specific biomarkers with near-infrared (NIR) fluorescent probes can help inaccurate diagnosis. Hydrogen sulfide (H2S) has been reported to be involved in many physiological and pathological processes and is considered as one of the key gasotransmitters during the development of cancer. To achieve specific H2S detection in cancer cells, we reported a biotin-guided NIR fluorescent sensor P1 targeting a cancer cell surface biomarker, based on the H2S-specific thiolysis of the NBD-amine-hemicyanine conjugate. The probe showed a fast turn-on signal at 754 nm upon H2S activation and good selectivity towards H2S over millimolar levels of other biothiols. We successfully employed P1 to image endogenous H2S and demonstrated its tumor-targeting ability in live cells. P1 could differentiate multiple cancer cells with various levels of H2S from normal cells, indicating its potential for cancer imaging.

Fragmented mitochondrial genomes of seal lice (family Echinophthiriidae) and gorilla louse (family Pthiridae): frequent minichromosomal splits and a host switch of lice between seals.

BACKGROUND: The mitochondrial (mt) genomes of 15 species of sucking lice from seven families have been studied to date. These louse species have highly dynamic, fragmented mt genomes that differ in the number of minichromosomes, the gene content, and gene order in a minichromosome between families and even between species of the same genus. RESULTS: In the present study, we analyzed the publicly available data to understand mt genome fragmentation in seal lice (family Echinophthiriidae) and gorilla louse, Pthirus gorillae (family Pthiridae), in particular the role of minichromosome split and minichromosome merger in the evolution of fragmented mt genomes. We show that 1) at least three ancestral mt minichromosomes of sucking lice have split in the lineage leading to seal lice, 2) one minichromosome ancestral to primate lice has split in the lineage to the gorilla louse, and 3) two ancestral minichromosomes of seal lice have merged in the lineage to the northern fur seal louse. Minichromosome split occurred 15-16 times in total in the lineages leading to species in six families of sucking lice investigated. In contrast, minichromosome merger occurred only four times in the lineages leading to species in three families of sucking lice. Further, three ancestral mt minichromosomes of sucking lice have split multiple times independently in different lineages of sucking lice. Our analyses of mt karyotypes and gene sequences also indicate the possibility of a host switch of crabeater seal louse to Weddell seals. CONCLUSIONS: We conclude that: 1) minichromosome split contributes more than minichromosome merger in mt genome fragmentation of sucking lice, and 2) mt karyotype comparison helps understand the phylogenetic relationships between sucking louse species.

Cysteine-Activated Small-Molecule H2Se Donors Inspired by Synthetic H2S Donors.

The importance of selenium (Se) in biology and health has become increasingly clear. Hydrogen selenide (H2Se), the biologically available and active form of Se, is suggested to be an emerging nitric oxide (NO)-like signaling molecule. Nevertheless, the research on H2Se chemical biology has technique difficulties due to the lack of well-characterized and controllable H2Se donors under physiological conditions, as well as a robust assay for direct H2Se quantification. Motivated by these needs, here, we demonstrate that selenocyclopropenones and selenoamides are tunable donor motifs that release H2Se upon reaction with cysteine (Cys) at pH 7.4 and that structural modifications enable the rate of Cys-mediated H2Se release to be tuned. We monitored the reaction pathways for the H2Se release and confirmed H2Se generation qualitatively using different methods. We further developed a quantitative assay for direct H2Se trapping and quantitation in an aqueous solution, which should also be operative for investigating future H2Se donor motifs. In addition, we demonstrate that arylselenoamide has the capability of Cys-mediated H2Se release in cellular environments. Importantly, mechanistic investigations and density functional theory (DFT) calculations illustrate the plausible pathways of Cys-activated H2Se release from arylselenoamides in detail, which may help understand the mechanistic issues of the H2S release from pharmacologically important arylthioamides. We anticipate that the well-defined chemistries of Cys-activated H2Se donor motifs will be useful for studying Se biology and for development of new H2Se donors and bioconjugate techniques.

Frequent tRNA gene translocation towards the boundaries with control regions contributes to the highly dynamic mitochondrial genome organization of the parasitic lice of mammals.

BACKGROUND: The typical single-chromosome mitochondrial (mt) genome of animals has fragmented into multiple minichromosomes in the lineage Mitodivisia, which contains most of the parasitic lice of eutherian mammals. These parasitic lice differ from each other even among congeneric species in mt karyotype, i.e. the number of minichromosomes, and the gene content and gene order in each minichromosome, which is in stark contrast to the extremely conserved single-chromosome mt genomes across most animal lineages. How fragmented mt genomes evolved is still poorly understood. We use Polyplax sucking lice as a model to investigate how tRNA gene translocation shapes the dynamic mt karyotypes. RESULTS: We sequenced the full mt genome of the Asian grey shrew louse, Polyplax reclinata. We then inferred the ancestral mt karyotype for Polyplax lice and compared it with the mt karyotypes of the three Polyplax species sequenced to date. We found that tRNA genes were entirely responsible for mt karyotype variation among these three species of Polyplax lice. Furthermore, tRNA gene translocation observed in Polyplax lice was only between different types of minichromosomes and towards the boundaries with the control region. A similar pattern of tRNA gene translocation can also been seen in other sucking lice with fragmented mt genomes. CONCLUSIONS: We conclude that inter-minichromosomal tRNA gene translocation orientated towards the boundaries with the control region is a major contributing factor to the highly dynamic mitochondrial genome organization in the parasitic lice of mammals.

Fragmented mitochondrial genomes evolved in opposite directions between closely related macaque louse Pedicinus obtusus and colobus louse Pedicinus badii.

We report for the first time the fragmented mitochondrial (mt) genomes of two Pedicinus species: Pedicinus obtusus and Pedicinus badii, and compared them with the lice of humans and chimpanzees. Despite being congeneric, the two monkey lice are distinct from each other in mt karyotype. The variation in mt karyotype between the two Pedicinus lice is the most pronounced among the congeneric species of sucking lice observed to date and is attributable to the opposite directions between them in mt karyotype evolution. Two of the inferred ancestral mt minichromosomes of the higher primate lice merged as one in the macaque louse whereas one of the ancestral minichromosomes split into two in the colobus louse after these two species diverged from their most recent common ancestor. Our results showed that mt genome fragmentation was a two-way process in the higher primate lice, and minichromosome merger was more common than previously thought.