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

Inhibition of Microsomal Prostaglandin E2 Synthase Reduces Collagen Deposition in Melanoma Tumors and May Improve Immunotherapy Efficacy by Reducing T-cell Exhaustion

The arachidonic acid pathway participates in immunosuppression in various types of cancer. Our previous observation detailed that microsomal prostaglandin E2 synthase 1 (mPGES-1), an enzyme downstream of cyclooxygenase 2 (COX-2), limited antitumor immunity in melanoma; in addition, genetic depletion of mPGES-1 specifically enhanced immune checkpoint blockade therapy. The current study set out to distinguish the roles of mPGES-1 from those of COX-2 in tumor immunity and determine the potential of mPGES-1 inhibitors for reinforcing immunotherapy in melanoma. Genetic deletion of mPGES-1 showed different profiles of prostaglandin metabolites from that of COX-2 deletion. In our syngeneic mouse model, mPGES-1-deficient cells exhibited similar tumorigenicity to that of COX-2-deficient cells, despite a lower ability to suppress PGE2 synthesis by mPGES-1 depletion, indicating the presence of factors other than PGE2 that are likely to regulate tumor immunity. RNA-sequencing analysis revealed that mPGES-1 depletion reduced the expressions of collagen-related genes, which have been found to be associated with immunosuppressive signatures. In our mouse model, collagen was reduced in mPGES-1-deficient tumors, and phenotypic analysis of tumor-infiltrating lymphocytes indicated that mPGES-1-deficient tumors had fewer TIM3+ exhausted CD8+ T cells compared with COX-2-deficient tumors. CAY10678, an mPGES-1 inhibitor, was equivalent to celecoxib, a selective COX-2 inhibitor, in reinforcing anti-PD-1 treatment. Our study indicates that mPGES-1 inhibitors represent a promising adjuvant for immunotherapies in melanoma by reducing collagen deposition and T-cell exhaustion

Monkeys mutant for PKD1 recapitulate human autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) caused by PKD1 mutations is one of the most common hereditary disorders. However, the key pathological processes underlying cyst development and exacerbation in pre-symptomatic stages remain unknown, because rodent models do not recapitulate critical disease phenotypes, including disease onset in heterozygotes. Here, using CRISPR/Cas9, we generate ADPKD models with PKD1 mutations in cynomolgus monkeys. As in humans and mice, near-complete PKD1 depletion induces severe cyst formation mainly in collecting ducts. Importantly, unlike in mice, PKD1 heterozygote monkeys exhibit cyst formation perinatally in distal tubules, possibly reflecting the initial pathology in humans. Many monkeys in these models survive after cyst formation, and cysts progress with age. Furthermore, we succeed in generating selective heterozygous mutations using allele-specific targeting. We propose that our models elucidate the onset and progression of ADPKD, which will serve as a critical basis for establishing new therapeutic strategies, including drug treatments

Long-term follow-up of production of IgM and IgG antibodies against SARS-CoV-2 among patients with COVID-19

The patients diagnosed with coronavirus disease 2019 （COVID-19） produce IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2）. However, the frequency and duration of antibody production still need to be fully understood. In the present study, we investigated the duration of antibody production after SARS-CoV-2 infection. The patients diagnosed with COVID-19 were monitored over twelve months for the production of SARS-CoV-2 IgM and IgG antibodies, and the characteristics of these patients were examined. Forty-five patients diagnosed with COVID-19 were enrolled, and thirty-four patients were followed up until they tested negative for SARS-CoV-2 IgM and IgG antibodies or up to twelve months after the date of a negative SARS-CoV-2 polymerase chain reaction （PCR） result. The positivity rates of SARS-CoV-2 IgM and IgG antibodies were 27.3％ and 68.2％ when SARS-CoV-2 PCR was negative, 20.6％ and 70.6％ after one month, 8.8％ and 52.9％ after three months, and 0.0％ and 14.7％ after six months, respectively. Moreover, we compared patients with milder conditions who did not require oxygen administration with those with severe conditions which required oxygen administration. The positivity rate of SARS-CoV-2 IgG antibodies was significantly higher in patients with severe conditions than in those with milder conditions on the date of a negative SARS-CoV-2 PCR result and after one month and three months, but not after six months. Patients with more severe COVID-19 produced more SARS-CoV-2 IgG antibodies. Moreover, it is suggested that the duration of IgG antibody production is independent of COVID-19 severity

エースアタッカーへのトス技術に関する事例研究 : 2011ワールドカップ男子大会における日本対ポーランド戦の映像分析

バレーボールのエースアタッカーは,熟練者のチームでも初心者レベルのチームにおいても攻撃の中心である.複数のアタッカーが攻撃を仕掛けるコンビネーション攻撃においても,打撃回数が多く,ゲームの競り合い場面ではチームの勝敗を託してトスを上げる存在である.その場合は,相手チームのマークがついていることを承知の上でトスを上げている時もある.従ってセッターのトスワークにおいては,エースアタッカーへ上げるトスは,ブロッカーをふるような巧いトスよりもエースアタッカーが打ち易い,換言すれば丁寧に良いトスを上げることが重要であると考えられる. 小野ほか(2002)は,女子大学生の熟練者と未熟練者を被験者にして落下させたボールを直上トスさせる上肢の動きをハイスピードカメラで撮影し3次元動作分析している.また橋原と佐賀野(2004)は,大学女子選手のセッター3名に通常のジャンプトスとボール保持時間を長くしたジャンプトスを行わせトス動作を3次元分析している.そして小野ほか,橋原と佐賀野の両研究とも,ボール接触時間を長くすることは,ボールコントロールを高め,巧いセッターの条件になると示唆している.また横矢ほか(2010)は,大学男子選手のセッター3名にレシーブ返球されたボールをレフトサイドに設置した的を目標にトスさせることによりトスの正確性に関する研究を行っている。しかしながら,これまで競技中のセッターのトス動作を定量分析した研究は無く,ゲーム場面においてセッターが実際どのくらい正確な位置にトスを上げているのか,そしてコントロール良くトスを上げるためにセッターはどのような動きをしているか等については,一般化できる資料が整っていないのが現状である. そこで本研究の目的は,バレーボールの技術を身に付けていて,それが発揮されていると考えられる,国際大会競技中の選手の動きを3次元映画分析することにより,エースアタッカーへ上げるセッターのトス技術を明らかにして,今後のバレーボール指導における資料を得ることである

Identification of CD74 isoforms that complex with CD44 to initiate Title of the Poster Presentation Goes Here the oncogenic signaling pathway in melanoma

https://openworks.mdanderson.org/sumexp21/1045/thumbnail.jp