Left–Right Reversal Recurrently Evolved Regardless of Diaphanous-Related Formin Gene Duplication or Loss in Snails

Bilateria exhibit whole-body handedness in internal structure. This left–right polarity is evolutionarily conserved with virtually no reversed extant lineage, except in molluscan Gastropoda. Phylogenetically independent snail groups contain both clockwise-coiled (dextral) and counterclockwise-coiled (sinistral) taxa that are reversed from each other in bilateral handedness as well as in coiling direction. Within freshwater Hygrophila, Lymnaea with derived dextrality have diaphanous related formin (diaph) gene duplicates, while basal sinistral groups possess one diaph gene. In terrestrial Stylommatophora, dextral Bradybaena also have diaph duplicates. Defective maternal expression of one of those duplicates gives rise to sinistral hatchlings in Lymnaea and handedness-mixed broods in Bradybaena, through polarity change in spiral cleavage of embryos. These findings led to the hypothesis that diaph duplication was crucial for the evolution of dextrality by reversal. The present study discovered that diaph duplication independently occurred four times and its duplicate became lost twice in gastropods. The dextrality of Bradybaena represents the ancestral handedness conserved across gastropods, unlike the derived dextrality of Lymnaea. Sinistral lineages recurrently evolved by reversal regardless of whether diaph had been duplicated. Amongst the seven formin gene subfamilies, diaph has most thoroughly been conserved across eukaryotes of the 14 metazoan phyla and choanoflagellate. Severe embryonic mortalities resulting from insufficient expression of the duplicate in both of Bradybaena and Lymnaea also support that diaph duplicates bare general roles for cytoskeletal dynamics other than controlling spiralian handedness. Our study rules out the possibility that diaph duplication or loss played a primary role for reversal evolution.journal articl

Microstructure of reaction rim of garnet amphibolites from the Lützow-Holm Complex at Ongul Island

第3回極域科学シンポジウム/第32回極域地学シンポジウム 11月30日（金） 国立極地研究所 ３階ラウン

市販茶系飲料の抗変異原性と抗変異原性成分の定量

Sep-pak C18 extracts of nineteen commercially available tea drinks were examined for inhibitory effects on the mutagenicity for three nitroarenes using umu-test. Antimutagenic activity of tea drinks increased in the following order: blend tea drinks < green tea drinks < oolong tea drinks. Furthermore, anti-mutagens (EGC, C, EGCG, EC, ECG, ascorbic acid, gallic acid and caffeine) concentrations of nineteen commercially available tea drinks were determined by HPLC combined with UV detector and electro-chemical detector. Higher concentrations of EGCG and EGC were detected in green tea drinks than oolong tea drinks. Total mean concentration of five catechins in oolong tea drinks was less than half of one in green tea drinks. These results suggest that there is no correlation between antimutagenicity for nitroarenes and catechin concentrations in commercially available tea drinks

Non-missense variants of KCNH2 show better outcomes in type 2 long QT syndrome

AIMS: More than one-third of type 2 long QT syndrome (LQT2) patients carry KCNH2 non-missense variants that can result in haploinsufficiency (HI), leading to mechanistic loss-of-function. However, their clinical phenotypes have not been fully investigated. The remaining two-thirds of patients harbour missense variants, and past studies uncovered that most of these variants cause trafficking deficiency, resulting in different functional changes: either HI or dominant-negative (DN) effects. In this study, we examined the impact of altered molecular mechanisms on clinical outcomes in LQT2 patients. METHODS AND RESULTS: We included 429 LQT2 patients (234 probands) carrying a rare KCNH2 variant from our patient cohort undergoing genetic testing. Non-missense variants showed shorter corrected QT (QTc) and less arrhythmic events (AEs) than missense variants. We found that 40% of missense variants in this study were previously reported as HI or DN. Non-missense and HI-groups had similar phenotypes, while both exhibited shorter QTc and less AEs than the DN-group. Based on previous work, we predicted the functional change of the unreported variants-whether they cause HI or DN via altered functional domains-and stratified them as predicted HI (pHI)- or pDN-group. The pHI-group including non-missense variants exhibited milder phenotypes compared to the pDN-group. Multivariable Cox model showed that the functional change was an independent risk of AEs (P = 0.005). CONCLUSION: Stratification based on molecular biological studies enables us to better predict clinical outcomes in the patients with LQT2

Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization

RBM20 is a major regulator of heart-specific alternative pre-mRNA splicing of TTN encoding a giant sarcomeric protein titin. Mutation in RBM20 is linked to autosomal-dominant familial dilated cardiomyopathy (DCM), yet most of the RBM20 missense mutations in familial and sporadic cases were mapped to an RSRSP stretch in an arginine/serine-rich region of which function remains unknown. In the present study, we identified an R634W missense mutation within the stretch and a G1031X nonsense mutation in cohorts of DCM patients. We demonstrate that the two serine residues in the RSRSP stretch are constitutively phosphorylated and mutations in the stretch disturb nuclear localization of RBM20. Rbm20 S637A knock-in mouse mimicking an S635A mutation reported in a familial case showed a remarkable effect on titin isoform expression like in a patient carrying the mutation. These results revealed the function of the RSRSP stretch as a critical part of a nuclear localization signal and offer the Rbm20 S637A mouse as a good model for in vivo study

A novel mitochondrial DnaJ/Hsp40 family protein BIL2 promotes plant growth and resistance against environmental stress in brassinosteroid signaling

Funding Information: Acknowledgments We thank Dr. Tsuyoshi Nakagawa (Shimane University) for the gift of the gateway vectors, pGWB2, pGWB80, pGWB5, and pGWB3. This work was supported in part by funding from the Program for Promotion of Basic Research Activities for Innovation Bioscience (PROBRAIN) to T.N. and T.A., and CREST, Japan Science and Technology Agency to T.N. and T.A.Plant steroid hormones, brassinosteroids, are essential for growth, development and responses to environmental stresses in plants. Although BR signaling proteins are localized in many organelles, i.e., the plasma membrane, nuclei, endoplasmic reticulum and vacuole, the details regarding the BR signaling pathway from perception at the cellular membrane receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) to nuclear events include several steps. Brz (Brz220) is a specific inhibitor of BR biosynthesis. In this study, we used Brz-mediated chemical genetics to identify Brz-insensitive-long hypocotyls 2-1D (bil2-1D). The BIL2 gene encodes a mitochondrial-localized DnaJ/Heat shock protein 40 (DnaJ/Hsp40) family, which is involved in protein folding. BIL2-overexpression plants (BIL2-OX) showed cell elongation under Brz treatment, increasing the growth of plant inflorescence and roots, the regulation of BR-responsive gene expression and suppression against the dwarfed BRI1-deficient mutant. BIL2-OX also showed resistance against the mitochondrial ATPase inhibitor oligomycin and higher levels of exogenous ATP compared with wild-type plants. BIL2 participates in resistance against salinity stress and strong light stress. Our results indicate that BIL2 induces cell elongation during BR signaling through the promotion of ATP synthesis in mitochondria.Peer reviewe

イヌノウユライシンケイエイヨウインシ (BDNF) イデンシ ノ タケイケンサク オヨビ イチエンキタガタ (-72G>A,60C>A) ト カツドウセイ キョウフセイスコア トノ カンレンセイ

本研究ではイヌの行動特性関連候補遺伝子としてBDNF遺伝子に着目した。多型検索を行った結果,6箇所の一塩基多型(SNPs;-2452G>C,-2439A>T,-2260T>C,-139C>T,-72G>Aおよび60C>A)が特定され,-2452G>C多型と-2439A>T多型,-72G>A多型と60C>A多型の間でそれぞれ高率な連鎖が確認された。また,-72G>Aおよび同義置換であることが推測された60C>Aについては,活動性-恐怖性スコアとの間に有意な関連が認められた。The present study demonstrated polymorphism screening of canine brain derived neurotrophic factor gene as one of behavioral trait relatives. We identified six novel single nucleotide polymorphisms (SNPs ; -2452G>C, -2439A>T, -2260T>C, -139C>T, -72G>A and 60C>A), -2452G>C and -2439A>T were highly linked as well as -72G>A and 60C>A. The statistical analyses revealed that and the -72G>A and 60C>A (60C>A as synonymous mutation), were significantly associated with `activeness-fearfulness discrimination scores\u27