Development and validation of a prognostic model for non-lung cancer death in elderly patients treated with stereotactic body radiotherapy for non-small cell lung cancer

This study sought to develop and validate a prognostic model for non-lung cancer death (NLCD) in elderly patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Patients aged ≥65 diagnosed with NSCLC (Tis-4N0M0), tumor diameter ≤5 cm and SBRT between 1998 and 2015 were retrospectively registered from two independent institutions. One institution was used for model development (arm D, 353 patients) and the other for validation (arm V, 401 patients). To identify risk factors for NLCD, multiple regression analysis on age, sex, performance status (PS), body mass index (BMI), Charlson comorbidity index (CCI), tumor diameter, histology and T-stage was performed on arm D. A score calculated using the regression coefficient was assigned to each factor and three risk groups were defined based on total score. Scores of 1.0 (BMI ≤18.4), 1.5 (age ≥ 5), 1.5 (PS ≥2), 2.5 (CCI 1 or 2) and 3 (CCI ≥3) were assigned, and risk groups were designated as low (total ≤ 3), intermediate (3.5 or 4) and high (≥4.5). The cumulative incidences of NLCD at 5 years in the low, intermediate and high-risk groups were 6.8, 23 and 40% in arm D, and 23, 19 and 44% in arm V, respectively. The AUC index at 5 years was 0.705 (arm D) and 0.632 (arm V). The proposed scoring system showed usefulness in predicting a high risk of NLCD in elderly patients treated with SBRT for NSCLC

Mesozoic origin and ‘out-of-India’ radiation of ricefishes (Adrianichthyidae)

The Indian subcontinent has an origin geologically different from Eurasia, but many terrestrial animal and plant species on it have congeneric or sister species in other parts of Asia, especially in the Southeast. This faunal and floral similarity between India and Southeast Asia is explained by either of the two biogeographic scenarios, ‘into-India’ or ‘out-of-India’. Phylogenies based on complete mitochondrial genomes and five nuclear genes were undertaken for ricefishes (Adrianichthyidae) to examine which of these two biogeographic scenarios fits better. We found that Oryzias setnai, the only adrianichthyid distributed in and endemic to the Western Ghats, a mountain range running parallel to the western coast of the Indian subcontinent, is sister to all other adrianichthyids from eastern India and Southeast–East Asia. Divergence time estimates and ancestral area reconstructions reveal that this western Indian species diverged in the late Mesozoic during the northward drift of the Indian subcontinent. These findings indicate that adrianichthyids dispersed eastward ‘out-of-India’ after the collision of the Indian subcontinent with Eurasia, and subsequently diversified in Southeast–East Asia. A review of geographic distributions of ‘out-of-India’ taxa reveals that they may have largely fuelled or modified the biodiversity of Eurasia.journal articl

CRISPR/Cas9-based heritable targeted mutagenesis in Thermobia domestica: A genetic tool in an apterygote development model of wing evolution

Despite previous developmental studies on basally branching wingless insects and crustaceans, the evolutionary origin of insect wings remains controversial. Knowledge regarding genetic regulation of tissues hypothesized to have given rise to wings would help to elucidate how ancestral development changed to allow the evolution of true wings. However, genetic tools available for basally branching wingless species are limited. The firebrat Thermobia domestica is an apterygote species, phylogenetically related to winged insects. T. domestica presents a suitable morphology to investigate the origin of wings, as it forms the tergal paranotum, from which wings are hypothesized to have originated. Here we report the first successful CRISPR/Cas9-based germline genome editing in T. domestica. We provide a technological platform to understand the development of tissues hypothesized to have given rise to wings in an insect with a pre-wing evolution body plan

pnp4a Is the Causal Gene of the Medaka Iridophore Mutant guanineless

See-through medaka lines are suitable for observing internal organs throughout life. They were bred by crossing multiple color mutants. However, some of the causal genes for these mutants have not been identified. The medaka has four pigment cell types: black melanophores, yellow xanthophores, white leucophores, and silvery iridophores. The causal genes of melanophore, xanthophore, and leucophore mutants have been elucidated, but the causal gene for the iridophore mutant remains unknown. Here, we describe the iridophore mutant, guanineless (gu), which exhibits a strong reduction in visible iridophores throughout its larval to adult stages. The gu locus was previously mapped to chromosome 5, but was located near the telomeric region, making it difficult to integrate into the chromosome. We sought the causal gene of gu using synteny analysis with the zebrafish genome and found a strong candidate, purine nucleoside phosphorylase 4a (pnp4a). Gene targeting and complementation testing showed that pnp4a is the causal gene of gu. This result will allow the establishment of inbred medaka strains or other useful strains with see-through phenotypes without major disruption in the genetic background of each strain

Evolution of Different Y Chromosomes in Two Medaka Species, Oryzias dancena and O. latipes

Although the sex-determining gene DMY has been identified on the Y chromosome in the medaka (Oryzias latipes), this gene is absent in most Oryzias species, suggesting that closely related species have different sex-determining genes. Here, we investigated the sex-determination mechanism in O. dancena, which does not possess the DMY gene. Since heteromorphic sex chromosomes have not been reported in this species, a progeny test of sex-reversed individuals produced by hormone treatment was performed. Sex-reversed males yielded all-female progeny, indicating that O. dancena has an XX/XY sex-determination system. To uncover the cryptic sex chromosomes, sex-linked DNA markers were screened using expressed sequence tags (ESTs) established in O. latipes. Linkage analysis of isolated sex-linked ESTs showed a conserved synteny between the sex chromosomes in O. dancena and an autosome in O. latipes. Fluorescence in situ hybridization (FISH) analysis of these markers confirmed that sex chromosomes of these species are not homologous. These findings strongly suggest an independent origin of sex chromosomes in O. dancena and O. latipes. Further analysis of the sex-determining region in O. dancena should provide crucial insights into the evolution of sex-determination mechanisms in vertebrates

Evidence for Different Origins of Sex Chromosomes in Closely Related Oryzias Fishes: Substitution of the Master Sex-Determining Gene

The medaka Oryzias latipes and its two sister species, O. curvinotus and O. luzonensis, possess an XX–XY sex-determination system. The medaka sex-determining gene DMY has been identified on the orthologous Y chromosome [O. latipes linkage group 1 (LG1)] of O. curvinotus. However, DMY has not been discovered in other Oryzias species. These results and molecular phylogeny suggest that DMY was generated recently [∼10 million years ago (MYA)] by gene duplication of DMRT1 in a common ancestor of O. latipes and O. curvinotus. We identified seven sex-linked markers from O. luzonensis (sister species of O. curvinotus) and constructed a sex-linkage map. Surprisingly, all seven sex-linked markers were located on an autosomal linkage group (LG12) of O. latipes. As suggested by the phylogenetic tree, the sex chromosomes of O. luzonensis should be “younger” than those of O. latipes. In the lineage leading to O. luzonensis after separation from O. curvinotus ∼5 MYA, a novel sex-determining gene may have arisen and substituted for DMY. Oryzias species should provide a useful model for evolution of the master sex-determining gene and differentiation of sex chromosomes from autosomes