Identification of glycine betaine as a host-derived molecule required for the vegetative proliferation of the protozoan parasite Perkinsus olseni

Perkinsus olseni is an industrially significant protozoan parasite of Manila clam, Ruditapes philippinarum. So far, various media, based on Dulbecco's Modified Eagle Medium and Ham's F-12 nutrient mixture with supplementation of fetal bovine serum (FBS), have been developed to proliferate the parasitizing trophozoite stage of P. olseni. The present study showed that P. olseni did not proliferate in FBS-deficient Perkinsus broth medium (PBMΔF), but proliferated well in PBMΔF supplemented with tissue extract of host Manila clams, indicating that FBS and Manila clam tissue contained molecule(s) required for P. olseni proliferation. Preliminary characterization suggested that the host-derived molecule(s) was a heat-stable molecule(s) with a molecular weight of less than 3 kDa, and finally a single molecule required for the proliferation was purified by high-performance liquid chromatography processes. High-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance analyses identified this molecule as glycine betaine (=trimethylglycine), and the requirement of this molecule for P. olsseni proliferation was confirmed by an assay using chemically synthesized, standard glycine betaine. Although glycine betaine was required for the proliferation of all examined Perkinsus species, supplementation of glycine betaine precursors, such as choline and betaine aldehyde, enhanced the proliferation of 4 Perkinsus species (P. marinus, P. chesapeaki, P. mediterraneus and P. honshuensis), but not of 2 others (P. olseni and P. beihaiensis). Thus, it was concluded that the ability to biosynthesise glycine betaine from its precursors varied among Perkinsus species, and that P. olseni and P. beihaiensis lack the ability required to biosynthesize glycine betaine for proliferation

G-compass: a web-based comparative genome browser between human and other vertebrate genomes

Summary: G-compass is designed for efficient comparative genome analysis between human and other vertebrate genomes. The current version of G-compass allows us to browse two corresponding genomic regions between human and another species in parallel. One-to-one evolutionarily conserved regions (i.e. orthologous regions) between species are highlighted along the genomes. Information such as locations of duplicated regions, copy number variations and mammalian ultra-conserved elements is also provided. These features of G-compass enable us to easily determine patterns of genomic rearrangements and changes in gene orders through evolutionary time. Since G-compass is a satellite database of H-InvDB, which is a comprehensive annotation resource for human genes and transcripts, users can easily refer to manually curated functional annotations and other abundant biological information for each human transcript. G-compass is expected to be a valuable tool for comparing human and model organisms and promoting the exchange of functional information

Tuning of Sry expression by H3K9 methylation and demethylation

Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the Sry locus in embryonic gonads, thereby compromising Sry expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the Sry locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct Sry expression. Here we identified the GLP/G9a H3K9 methyltransferase complex as the enzyme catalyzing H3K9 methylation at the Sry locus. Based on this finding, we tried to rescue the sex-reversal phenotype of Jmjd1a-deficient mice by modulating GLP/G9a complex activity. A heterozygous GLP mutation rescued the sex-reversal phenotype of Jmjd1a-deficient mice by restoring Sry expression. The administration of a chemical inhibitor of GLP/G9a enzyme into Jmjd1a-deficient embryos also successfully rescued sex reversal. Our study not only reveals the molecular mechanism underlying the tuning of Sry expression but also provides proof on the principle of therapeutic strategies based on the pharmacological modulation of epigenetic balance

Intermittent X-linked thrombocytopenia with a novel WAS gene mutation

X-linked thrombocytopenia (XLT) is caused by mutations in the WAS gene and characterized by thrombocytopenia with minimal or no immunodeficiency. Patients with XLT usually exhibit persistent thrombocytopenia, and intermittent thrombocytopenia has been described only in two families. Here, we report a patient with intermittent XLT carrying a novel missense mutation (Ala56Thr). He showed residual expression of Wiskott-Aldrich syndrome protein in the lymphocytes and platelets. There appeared to be an association between normal platelet numbers and a post infectious state. Our findings further support the importance of analysis of Wiskott-Aldrich syndrome protein in male patients who exhibit fluctuating courses of thrombocytopenia. Pediatr Blood Cancer 2014;61:746-748. © 2013 Wiley Periodicals, Inc

Nonlinear Excitation of Subcritical Instabilities in a Toroidal Plasma

In a collisionless plasma, it is known that linearly stable modes can be destabilized (subcritically) by the presence of structures in phase space. However, nonlinear growth requires the presence of a seed structure with a relatively large threshold in amplitude. We demonstrate that, in the presence of another, linearly unstable (supercritical) mode, wave-wave coupling can provide a seed, which is significantly below the threshold, but can still grow by (and only by) the collaboration of fluid and kinetic nonlinearities. By modeling the subcritical mode kinetically, and the impact of the supercritical mode by simple wave-wave coupling equations, it is shown that this new kind of subcritical instability can be triggered, even when the frequency of the supercritical mode is rapidly sweeping. The model is applied to the bursty onset of geodesic acoustic modes in a LHD experiment. The model recovers several key features such as relative amplitude, time scales, and phase relations. It suggests that the strongest bursts are subcritical instabilities, driven by this mechanism of combined fluid and kinetic nonlinearities

Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3.

植物由来成分であるプテロシンBはSIK3を阻害し変形性関節症の治療薬開発のリード化合物となる. 京都大学プレスリリース. 2016-03-31.Yahara, Y., Takemori, H., Okada, M. et al. Correction: Corrigendum: Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3. Nat Commun 7, 12117 (2016).Osteoarthritis is a common debilitating joint disorder. Risk factors for osteoarthritis include age, which is associated with thinning of articular cartilage. Here we generate chondrocyte-specific salt-inducible kinase 3 (Sik3) conditional knockout mice that are resistant to osteoarthritis with thickened articular cartilage owing to a larger chondrocyte population. We also identify an edible Pteridium aquilinum compound, pterosin B, as a Sik3 pathway inhibitor. We show that either Sik3 deletion or intraarticular injection of mice with pterosin B inhibits chondrocyte hypertrophy and protects cartilage from osteoarthritis. Collectively, our results suggest Sik3 regulates the homeostasis of articular cartilage and is a target for the treatment of osteoarthritis, with pterosin B as a candidate therapeutic

亜臨界高速イオン励起モードの非線形励起, 亜臨界高速イオン励起モードの非線形励起

In collisionless plasma, it is known that linearly stable modes can be destabilized (subcritically) by the presence of structures in phase-space. The growth of such structures is a nonlinear, kinetic mechanism, which provides a channel for free-energy extraction, different from conventional inverse Landau damping. However, such nonlinear growth requires the presence of a seed structure with a relatively large threshold in amplitude. We demonstrate that, in the presence of another, linearly unstable (supercritical) mode, wave–wave coupling can provide a seed, which can lead to subcritical instability by either one of two mechanisms. Both mechanisms hinge on a collaboration between fluid nonlinearity and kinetic nonlinearity. If collisional velocity diffusion is low enough, the seed provided by the supercritical mode overcomes the threshold for nonlinear growth of phase-space structure. Then, the supercritical mode triggers the conventional subcritical instability. If collisional velocity diffusion is too large, the seed is significantly below the threshold, but can still grow by a sustained collaboration between fluid and kinetic nonlinearities. Both of these subcritical instabilities can be triggered, even when the frequency of the supercritical mode is rapidly sweeping. These results were obtained by modeling the subcritical mode kinetically, and the impact of the supercritical mode by simple wave–wave coupling equations. This model is applied to bursty onset of geodesic acoustic modes in an LHD experiment. The model recovers several key features such as relative amplitude, timescales, and phase relations. It suggests that the strongest bursts are subcritical instabilities, with sustained collaboration between fluid and kinetic nonlinearities