The genotype-dependent phenotypic landscape of quinoa in salt tolerance and key growth traits

スーパー作物キヌアの多様性を解明 --高い環境適応性と優れた栄養特性をもつキヌアの品種改良に期待--. 京都大学プレスリリース. 2020-10-15.Cultivation of quinoa (Chenopodium quinoa), an annual pseudocereal crop that originated in the Andes, is spreading globally. Because quinoa is highly nutritious and resistant to multiple abiotic stresses, it is emerging as a valuable crop to provide food and nutrition security worldwide. However, molecular analyses have been hindered by the genetic heterogeneity resulting from partial outcrossing. In this study, we generated 136 inbred quinoa lines as a basis for the molecular identification and characterization of gene functions in quinoa through genotyping and phenotyping. Following genotyping-by-sequencing analysis of the inbred lines, we selected 5, 753 single-nucleotide polymorphisms (SNPs) in the quinoa genome. Based on these SNPs, we show that our quinoa inbred lines fall into three genetic sub-populations. Moreover, we measured phenotypes, such as salt tolerance and key growth traits in the inbred quinoa lines and generated a heatmap that provides a succinct overview of the genotype–phenotype relationship between inbred quinoa lines. We also demonstrate that, in contrast to northern highland lines, most lowland and southern highland lines can germinate even under high salinity conditions. These findings provide a basis for the molecular elucidation and genetic improvement of quinoa and improve our understanding of the evolutionary process underlying quinoa domestication

Exome Sequencing Reveals a Homozygous SYT14 Mutation in Adult-Onset, Autosomal-Recessive Spinocerebellar Ataxia with Psychomotor Retardation

Autosomal-recessive cerebellar ataxias (ARCAs) are clinically and genetically heterogeneous disorders associated with diverse neurological and nonneurological features that occur before the age of 20. Currently, mutations in more than 20 genes have been identified, but approximately half of the ARCA patients remain genetically unresolved. In this report, we describe a Japanese family in which two siblings have slow progression of a type of ARCA with psychomotor retardation. Using whole-exome sequencing combined with homozygosity mapping, we identified a homozygous missense mutation in SYT14, encoding synaptotagmin XIV (SYT14). Expression analysis of the mRNA of SYT14 by a TaqMan assay confirmed that SYT14 mRNA was highly expressed in human fetal and adult brain tissue as well as in the mouse brain (especially in the cerebellum). In an in vitro overexpression system, the mutant SYT14 showed intracellular localization different from that of the wild-type. An immunohistochemical analysis clearly showed that SYT14 is specifically localized to Purkinje cells of the cerebellum in humans and mice. Synaptotagmins are associated with exocytosis of secretory vesicles (including synaptic vesicles), indicating that the alteration of the membrane-trafficking machinery by the SYT14 mutation may represent a distinct pathomechanism associated with human neurodegenerative disorders

Identification of 45 New Neutron-Rich Isotopes Produced by In-Flight Fission of a 238U Beam at 345 MeV/nucleon

A search for new isotopes using in-flight fission of a 345 MeV/nucleon 238U beam has been carried out at the RI Beam Factory at the RIKEN Nishina Center. Fission fragments were analyzed and identified by using the superconducting in-flight separator BigRIPS. We observed 45 new neutron-rich isotopes: 71Mn, 73,74Fe, 76Co, 79Ni, 81,82Cu, 84,85Zn, 87Ga, 90Ge, 95Se, 98Br, 101Kr, 103Rb, 106,107Sr, 108,109Y, 111,112Zr, 114,115Nb, 115,116,117Mo, 119,120Tc, 121,122,123,124Ru, 123,124,125,126Rh, 127,128Pd, 133Cd, 138Sn, 140Sb, 143Te, 145I, 148Xe, and 152Ba

X-ray harmonic comb from relativistic electron spikes

X-ray devices are far superior to optical ones for providing nanometre spatial and attosecond temporal resolutions. Such resolution is indispensable in biology, medicine, physics, material sciences, and their applications. A bright ultrafast coherent X-ray source is highly desirable, for example, for the diffractive imaging of individual large molecules, viruses, or cells. Here we demonstrate experimentally a new compact X-ray source involving high-order harmonics produced by a relativistic-irradiance femtosecond laser in a gas target. In our first implementation using a 9 Terawatt laser, coherent soft X-rays are emitted with a comb-like spectrum reaching the 'water window' range. The generation mechanism is robust being based on phenomena inherent in relativistic laser plasmas: self-focusing, nonlinear wave generation accompanied by electron density singularities, and collective radiation by a compact electric charge. The formation of singularities (electron density spikes) is described by the elegant mathematical catastrophe theory, which explains sudden changes in various complex systems, from physics to social sciences. The new X-ray source has advantageous scalings, as the maximum harmonic order is proportional to the cube of the laser amplitude enhanced by relativistic self-focusing in plasma. This allows straightforward extension of the coherent X-ray generation to the keV and tens of keV spectral regions. The implemented X-ray source is remarkably easily accessible: the requirements for the laser can be met in a university-scale laboratory, the gas jet is a replenishable debris-free target, and the harmonics emanate directly from the gas jet without additional devices. Our results open the way to a compact coherent ultrashort brilliant X-ray source with single shot and high-repetition rate capabilities, suitable for numerous applications and diagnostics in many research fields

Notch3-dependent β-catenin signaling mediates EGFR TKI drug persistence in EGFR mutant NSCLC

EGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung cancer, but resistance universally develops. The involvement of β-catenin in EGFR TKI resistance has been previously reported, however, the precise mechanism by which β-catenin activation contributes to EGFR TKI resistance is not clear. Here, we show that EGFR inhibition results in the activation of β-catenin signaling in a Notch3-dependent manner, which facilitates the survival of a subset of cells that we call “adaptive persisters”. We previously reported that EGFR-TKI treatment rapidly activates Notch3, and here we describe the physical association of Notch3 with β-catenin, leading to increased stability and activation of β-catenin. We demonstrate that the combination of EGFR-TKI and a β-catenin inhibitor inhibits the development of these adaptive persisters, decreases tumor burden, improves recurrence free survival, and overall survival in xenograft models. These results supports combined EGFR-TKI and β-catenin inhibition in patients with EGFR mutant lung cancer

Low-Dose Intravenous Alteplase in Wake-Up Stroke

Background and Purpose—We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods—This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1). Results—Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P>0.999), respectively. Conclusions—No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions