12-<i>Epi</i>-9-deacetoxyxenicin, new cytotoxic diterpenoid from a Bornean soft coral, <i>Xenia</i> sp.

<p>One new compound, 12-<i>epi</i>-9-deacetoxyxenicin (<b>1</b>) along with a hydroperoxide product, 12-<i>epi</i>-9-deacetoxy-8-hydroperoxyxenicin (<b>2</b>) and two known sesquiterpenoids (<b>3</b>–<b>4</b>) were isolated from a population of Bornean soft coral <i>Xenia</i> sp. The structures of these secondary metabolites were elucidated based on their spectroscopic data. Compounds <b>1</b> and <b>2</b> showed cytotoxic activity against ATL cell line, S1T. In addition, compound <b>3</b> exhibited hyphal inhibition of <i>Lagenidium thermophilum</i>.</p

Identification of <i>trm2</i> mutation.

<p>A: Distribution of haplotypes around <i>trm2</i> in (TRM × TRMR)F1 × TRM backcross progeny. White boxes, animals heterozygous for TRM alleles. Black boxes, animals homozygous for TRM alleles. Number of backcross progeny specified underneath the haplotypes. B: Linkage and physical maps including <i>trm2</i>. <i>Parp8</i>, poly (ADP-ribose) polymerase family, member 8; <i>Emb</i>, embigin; <i>Mrps30</i>, mitochondrial ribosomal protein S30; <i>Fgf10</i>, fibroblast growth factor 10. C: Sequencing analysis in TRMR (upper) and TRM (lower) rats. A nucleotide change from C to T located in <i>Hcn1</i> exon 4 is indicated by arrow. The mutation results in an amino acid substitution of alanine (Ala) with valine (Val) at codon 354 of the HCN1 protein. D: Schematic representation of the HCN1 channel subunit. P-loop, pore region; CNBD, cyclic nucleotide-binding domain; black circle, A354V substitution located in the pore region. E: Representative current recordings of wild-type and A354V HCN1 channels. Right panel, hyperpolarization-induced currents measured at the end of the step pulse (-120 mV). Data are presented as the mean ± SEM of seven (wild-type) or six (A354V) experiments. **<i>P</i><0.01 <i>vs</i>. wild-type.</p

Immunohistochemical analysis of Fos expression in TRM rats.

<p>A: Schematic illustrations of brain sections selected for quantitative analysis of Fos-immunoreactivity. Anteroposterior distance from bregma is shown above each brain section. Filled boxes in each section indicate the areas analyzed. B: Numbers of Fos-immunoreactive neurons in various brain regions. Data show the mean ± SEM of four (TRM) or five (WTC) rats. *<i>P</i><0.05, **<i>P</i><0.01 <i>vs</i>. control (WTC).</p

Tremor inhibition by IO lesioning in TRM rats.

<p>A: Effects of IO lesioning on tremor induction in TRM rats. The duration and intensity of tremor was significantly suppressed 38 and 54 h after IO lesioning. Data are presented as the mean ± SEM of five animals. *<i>P</i><0.05 <i>vs</i>. pre-treatment control. B: Lesion sites in the brain sections.</p

TRM rat as a model of essential tremor.

<p>A: Representative EMG from TRM rats. Tremor is shown as a bold line above EMG. Lower panels show magnified EMG and its power frequency analysis (red bar). Calibration: 100 μV and 20 s (upper panel), 50 μV and 5 s (lower panel). B: Effects of anti-tremor agents on tremor incidence in TRM rats. Data are presented as the mean ± SEM of seven (propranolol and trihexyphenidyl) or six (phenobarbital) animals. *<i>P</i><0.05, **<i>P</i><0.01, <i>vs</i>. pre-drug control levels (pre).</p

Tremor induction by the HCN1 channel blocker ZD7288 in TRMR rats.

<p>A: Genetic components responsible for tremor development in our rat model of ET. TRM rats, carrying both the <i>tm</i> deletion (red) and the <i>Hcn1</i> mutation (blue), showed body tremors. TRMR rats, carrying the <i>tm</i> deletion but not the <i>Hcn1</i> mutation, showed no body tremors, but body tremors were induced when the selective HCN1 channel blocker ZD7288 was administered (see B, this figure). WTC rats, carrying the <i>Hcn1</i> mutation but not the <i>tm</i> deletion, showed no body tremors with or without administration of ZD7288 (see B, this figure). B: Effects of ZD7288 on tremor induction in nontremulous TRMR rats. Duration and intensity of tremor observed in TRMR rats that received vehicle or ZD7288. Data are presented as the mean ± SEM of seven (vehicle) or eight (ZD7288) animals. *<i>P</i><0.05, **<i>P</i><0.01 <i>vs</i>. pre-treatment control levels (pre).</p

A new isomaneonene derivative from the red alga <i>Laurencia</i> cf. <i>mariannensis</i>

Determining the structures of new natural products from marine species not only enriches our understanding of the diverse chemistry of these species, but can also lead to the discovery of compounds with novel and/or important biological activities. Herein, we describe the isolation of isomaneonene C (1), a new halogenated C15 acetogenin, and three known compounds, α-snyderol (2), cis-maneonene D (3), and isomaneonene B (4), from the organic extract obtained from the red alga Laurencia cf. mariannensis collected from Iheya Island, Okinawa, Japan. The structures of these secondary metabolites were elucidated spectroscopically. All compounds were inactive at 30 μg/disc against methicillin-resistant Staphylococcus aureus (MRSA) in combination treatment with a β-lactam drug, meropenem. </p

Identification of <i>trm2</i> mutation.

<p>A: Distribution of haplotypes around <i>trm2</i> in (TRM × TRMR)F1 × TRM backcross progeny. White boxes, animals heterozygous for TRM alleles. Black boxes, animals homozygous for TRM alleles. Number of backcross progeny specified underneath the haplotypes. B: Linkage and physical maps including <i>trm2</i>. <i>Parp8</i>, poly (ADP-ribose) polymerase family, member 8; <i>Emb</i>, embigin; <i>Mrps30</i>, mitochondrial ribosomal protein S30; <i>Fgf10</i>, fibroblast growth factor 10. C: Sequencing analysis in TRMR (upper) and TRM (lower) rats. A nucleotide change from C to T located in <i>Hcn1</i> exon 4 is indicated by arrow. The mutation results in an amino acid substitution of alanine (Ala) with valine (Val) at codon 354 of the HCN1 protein. D: Schematic representation of the HCN1 channel subunit. P-loop, pore region; CNBD, cyclic nucleotide-binding domain; black circle, A354V substitution located in the pore region. E: Representative current recordings of wild-type and A354V HCN1 channels. Right panel, hyperpolarization-induced currents measured at the end of the step pulse (-120 mV). Data are presented as the mean ± SEM of seven (wild-type) or six (A354V) experiments. **<i>P</i><0.01 <i>vs</i>. wild-type.</p

Auxin signaling through SCF^TIR1/AFBs mediates feedback regulation of IAA biosynthesis

<p>We previously reported that exogenous application of auxin to Arabidopsis seedlings resulted in downregulation of indole-3-acetic acid (IAA) biosynthesis genes in a feedback manner. In this study, we investigated the involvement of the SCF^TIR1/AFB-mediated signaling pathway in feedback regulation of the indole-3-pyruvic acid-mediated auxin biosynthesis pathway in Arabidopsis. Application of PEO-IAA, an inhibitor of the IAA signal transduction pathway, to wild-type seedlings resulted in increased endogenous IAA levels in roots. Endogenous IAA levels in the auxin-signaling mutants <i>axr2</i>-<i>1</i>, <i>axr3</i>-<i>3</i>, and <i>tir1</i>-<i>1afb1</i>-<i>1afb2</i>-<i>1afb3</i>-<i>1</i> also increased. Furthermore, <i>YUCCA</i> (<i>YUC</i>) gene expression was repressed in response to auxin treatment, and expression of <i>YUC7</i> and <i>YUC8</i> increased in response to PEO-IAA treatment. <i>YUC</i> genes were also induced in auxin-signaling mutants but repressed in <i>TIR1</i>-overexpression lines. These observations suggest that the endogenous IAA levels are regulated by auxin biosynthesis in a feedback manner, and the Aux/IAA and SCF^TIR1/AFB-mediated auxin-signaling pathway regulates the expression of <i>YUC</i> genes.</p