Infrared Spectroscopy of 15 Radio Galaxies at 2<z<2.6

Near-infrared spectra of 15 high-redshift radio galaxies (HzRGs) located at $2<z<2.6$ were obtained by the OH Airglow Suppressor spectrograph mounted on the Subaru telescope. The UV-optical line ratio diagnostic diagrams indicate that half of the observed HzRGs have extended emission-line regions with low metal abundance, photoionized by a flat-continuum active galactic nucleus such as a quasar. We also found two probable correlations between radio and rest-optical parameters: (1) HzRGs with massive hosts tend to have a redder rest-optical continuum, and (2) HzRGs with smaller radio sizes also show a redder optical continuum. On the basis of the correlations, the nature of HzRGs at $2<z<2.6$ is discussed.Comment: 23 pages, 7 figures, Corrected typos and style. Accepted for publication in ApJ (November 20, 2003

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves

Molecular Adaptation of rbcL in the Heterophyllous Aquatic Plant Potamogeton

Heterophyllous aquatic plants show marked phenotypic plasticity. They adapt to environmental changes by producing different leaf types: submerged, floating and terrestrial leaves. By contrast, homophyllous plants produce only submerged leaves and grow entirely underwater. Heterophylly and submerged homophylly evolved under selective pressure modifying the species-specific optima for photosynthesis, but little is known about the evolutionary outcome of habit. Recent evolutionary analyses suggested that rbcL, a chloroplast gene that encodes a catalytic subunit of RuBisCO, evolves under positive selection in most land plant lineages. To examine the adaptive evolutionary process linked to heterophylly or homophylly, we analyzed positive selection in the rbcL sequences of ecologically diverse aquatic plants, Japanese Potamogeton.Phylogenetic and maximum likelihood analyses of codon substitution models indicated that Potamogeton rbcL has evolved under positive Darwinian selection. The positive selection has operated specifically in heterophyllous lineages but not in homophyllous ones in the branch-site models. This suggests that the selective pressure on this chloroplast gene was higher for heterophyllous lineages than for homophyllous lineages. The replacement of 12 amino acids occurred at structurally important sites in the quaternary structure of RbcL, two of which (residue 225 and 281) were identified as potentially under positive selection.Our analysis did not show an exact relationship between the amino acid replacements and heterophylly or homophylly but revealed that lineage-specific positive selection acted on the Potamogeton rbcL. The contrasting ecological conditions between heterophyllous and homophyllous plants have imposed different selective pressures on the photosynthetic system. The increased amino acid replacement in RbcL may reflect the continuous fine-tuning of RuBisCO under varying ecological conditions

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Cytokinins Induce Prehaustoria Coordinately with Quinone Signals in the Parasitic Plant Striga hermonthica

Orobanchaceae parasitic plants are major threats to global food security, causing severe agricultural damage worldwide. Parasitic plants derive water and nutrients from their host plants through multicellular organs called haustoria. The formation of a prehaustorium, a primitive haustorial structure, is provoked by host-derived haustorium-inducing factors (HIFs). Quinones, including 2,6-dimethoxy-p-benzoquinone (DMBQ), are of the most potent HIFs for various species in Orobanchaceae, but except non-photosynthetic holoparasites, Phelipanche and Orobanche spp. Instead, cytokinin (CK) phytohormones were reported to induce prehaustoria in Phelipanche ramosa. However, little is known about whether CKs act as HIFs in the other parasitic species to date. Moreover, the signaling pathways for quinones and CKs in prehaustorium induction are not well understood. This study shows that CKs act as HIFs in the obligate parasite Striga hermonthica but not in the facultative parasite Phtheirospermum japonicum. Using chemical inhibitors and marker gene expression analysis, we demonstrate that CKs activate prehaustorium formation through a CK-specific signaling pathway that overlaps with the quinone HIF pathway at downstream in S. hermonthica. Moreover, host root exudates activated S. hermonthica CK biosynthesis and signaling genes, and DMBQ and CK inhibitors perturbed the prehaustorium-inducing activity of exudates, indicating that host root exudates include CKs. Our study reveals the importance of CKs for prehaustorium formation in obligate parasitic plants

MRI-based Glucose Assay Using Magnetic Nanoparticle Sensors.

Glucose sensors for NMR relaxometry and magnetic resonance imaging (MRI) can be used for the direct measurement of glucose in turbid biological specimens. Here, we proposed a magnetic glucose sensor based on superparamagnetic iron oxide (SPIO) nanoparticles conjugated to a mannopyranoside derivative and concanavalin A (ConA). The binding of mannopyranoside groups to ConA produced a nanoparticle cluster that was dissociated by competitive binding of glucose to ConA, resulting in changes in the transverse relaxation time (T) in a glucose-dependent manner. The sensor gave rise to significant T changes in physiological glucose levels of 3 - 8 mM at a nanoparticle concentration of 0.5 nM. Significant T responses were observed within 6 min of 5 mM glucose detection. Sensor-based MRI by a benchtop 1 tesla scanner permitted a measurement of multiple samples within 8 min. These results demonstrate that the relaxometric glucose sensor could lead to high throughput direct assay of blood samples by using a compact MRI scanner for point-of-care testing