BRZ-INSENSITIVE-LONG HYPOCOTYL8 inhibits kinase-mediated phosphorylation to regulate brassinosteroid signaling.

Glycogen synthase kinase 3 (GSK3) is an evolutionarily conserved serine/threonine protein kinase in eukaryotes. In plants, the GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2) functions as a central signaling node through which hormonal and environmental signals are integrated to regulate plant development and stress adaptation. BIN2 plays a major regulatory role in brassinosteroid (BR) signaling and is critical for phosphorylating/inactivating BRASSINAZOLE-RESISTANT 1 (BZR1), also known as BRZ-INSENSITIVE-LONG HYPOCOTYL 1 (BIL1), a master transcription factor of BR signaling, but the detailed regulatory mechanism of BIN2 action has not been fully revealed.

BPG4 regulates chloroplast development and homeostasis by suppressing GLK transcription factors and involving light and brassinosteroid signaling.

Chloroplast development adapts to the environment for performing suitable photosynthesis. Brassinosteroids (BRs), plant steroid hormones, have crucial effects on not only plant growth but also chloroplast development. However, the detailed molecular mechanisms of BR signaling in chloroplast development remain unclear.

RNA-dependent synthesis of ergosteryl-3β-O-glycine in Ascomycota expands the diversity of steryl-amino acids.

A wide range of bacteria possess virulence factors such as aminoacyl-tRNA transferases (ATTs) that are capable of rerouting aminoacyl-transfer RNAs away from protein synthesis to conjugate amino acids onto glycerolipids. We recently showed that, although these pathways were thought to be restricted to bacteria, higher fungi also possess ergosteryl-3β-O-L-aspartate synthases (ErdSs), which transfer the L-Asp moiety of aspartyl-tRNA onto the 3β-OH group of ergosterol (Erg), yielding ergosteryl-3β-O-L-aspartate (Erg-Asp). Here, we report the discovery, in fungi, of a second type of fungal sterol-specific ATTs, namely, ergosteryl-3β-O-glycine (Erg-Gly) synthase (ErgS).

Synthesis of aminoacylated ergosterols: A new lipid component of fungi.

Aminoacylated ergosterol such as 1-ergosteryl aspartate (Erg-Asp) is a new lipid component recently discovered in fungi. In order to study physiological functions of this novel sterol derivative and to develop potential antifungal agents, we established the method to synthesize aminoacylated ergosterol derivatives. Herein, we report the synthesis of Erg-Asp as well as some other aminoacylated ergosterols (Erg-Gly, Erg-Ala, Erg-Leu, Erg-Ile, and Erg-Val) using Boc protected amino acids.

Two Triterpene Synthases from Imperata cylindrica Catalyzing the Formation of a Pair of Diastereoisomers through Boat or Chair Cyclization.

Imperata cylindrica is known to produce a pair of triterpenes, isoarborinol and fernenol, that exhibit identical planar structures but possess opposite stereochemistry at six of the nine chiral centers. These differences arise from a boat or a chair cyclization of the B-ring of the substrate. Herein, we report the characterization of three OSC genes from I.

Plant-Specific Domains and Fragmented Sequences Imply Non-Canonical Functions in Plant Aminoacyl-tRNA Synthetases.

Aminoacyl-tRNA synthetases (aaRSs) play essential roles in protein translation. In addition, numerous aaRSs (mostly in vertebrates) have also been discovered to possess a range of non-canonical functions. Very few studies have been conducted to elucidate or characterize non-canonical functions of plant aaRSs.

RNA-dependent sterol aspartylation in fungi.

Diverting aminoacyl-transfer RNAs (tRNAs) from protein synthesis is a well-known process used by a wide range of bacteria to aminoacylate membrane constituents. By tRNA-dependently adding amino acids to glycerolipids, bacteria change their cell surface properties, which intensifies antimicrobial drug resistance, pathogenicity, and virulence. No equivalent aminoacylated lipids have been uncovered in any eukaryotic species thus far, suggesting that tRNA-dependent lipid remodeling is a process restricted to prokaryotes.

Allylic hydroxylation of triterpenoids by a plant cytochrome P450 triggers key chemical transformations that produce a variety of bitter compounds.

Cucurbitacins are highly oxygenated triterpenoids characteristic of plants in the family Cucurbitaceae and responsible for the bitter taste of these plants. Fruits of bitter melon () contain various cucurbitacins possessing an unusual ether bridge between C5 and C19, not observed in other Cucurbitaceae members. Using a combination of next-generation sequencing and RNA-Seq analysis and gene-to-gene co-expression analysis with the ConfeitoGUIplus software, we identified three P450 genes, , , and , expected to be involved in cucurbitacin biosynthesis.

Mechanism of Action of Prethioviridamide, an Anticancer Ribosomally Synthesized and Post-Translationally Modified Peptide with a Polythioamide Structure.

Thioviridamide, prethioviridamide, and JBIR-140, which are ribosomally synthesized and post-translationally modified peptides (RiPPs) possessing five thioamide bonds, induce selective apoptosis in various cancer cells, especially those expressing the adenovirus oncogene E1A. However, the target protein of this unique family of bioactive compounds was previously unknown. To investigate the mechanism of action, we adopted a combined approach of genome-wide shRNA library screening, transcriptome profiling, and biochemical identification of prethioviridamide-binding proteins.

Morning Home Blood Pressure and Cardiovascular Events in Japanese Hypertensive Patients.

SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated the benefit of achieving strict blood pressure control with a lower target blood pressure level in high-risk patients with hypertension. The aim of this post hoc analysis was to investigate the relationship between the 2-year average on-treatment home blood pressure and cardiovascular disease risk in subgroups stratified by risk status using data from the HONEST study (Home Blood Pressure Measurement With Olmesartan Naive Patients to Establish Standard Target Blood Pressure). Participants in the HONEST study (n=21 591) were stratified according to risk level as follows: SPRINT population (n=5823)-patients (≥50 years of age) without diabetes mellitus or prior stroke, with SPRINT-defined cardiovascular risk and systolic blood pressure (SBP) of ≥130 mm Hg; SPRINT-excluded high-risk population (n=5481)-patients with diabetes mellitus or prior stroke; and non-SPRINT low-risk population-all other patients in the HONEST study (n=10 287).

Identification of triterpene biosynthetic genes from Momordica charantia using RNA-seq analysis.

Cucurbitaceae plants contain characteristic triterpenoids. Momordica charantia, known as a bitter melon, contains cucurbitacins and multiflorane type triterpenes, which confer bitter tasting and exhibit pharmacological activities. Their carbon skeletons are biosynthesized from 2,3-oxidosqualene by responsible oxidosqualene cyclase (OSC).

Home blood pressure and cardiovascular outcomes in very elderly patients receiving antihypertensive drug therapy: a subgroup analysis of Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study.

The appropriate target blood pressure (BP) in elderly patients with hypertension remains uncertain. We investigated the relationship between morning home systolic blood pressure (MHSBP) during follow-up and cardiovascular (CV) risk in outpatients receiving olmesartan-based treatment aged <75 years (n = 16799) and ≥75 years (n = 4792) in the HONEST study. In the follow-up period (mean 2.

Biosynthesis of helvolic acid and identification of an unusual C-4-demethylation process distinct from sterol biosynthesis.

Fusidane-type antibiotics represented by helvolic acid, fusidic acid and cephalosporin P are a class of bacteriostatic agents, which have drawn renewed attention because they have no cross-resistance to commonly used antibiotics. However, their biosynthesis is poorly understood. Here, we perform a stepwise introduction of the nine genes from the proposed gene cluster for helvolic acid into Aspergillus oryzae NSAR1, which enables us to isolate helvolic acid (~20 mg L) and its 21 derivatives.

A quantitative shRNA screen identifies ATP1A1 as a gene that regulates cytotoxicity by aurilide B.

Genome-wide RNA interference (RNAi) with pooled and barcoded short-hairpin RNA (shRNA) libraries provides a powerful tool for identifying cellular components that are relevant to the modes/mechanisms of action (MoA) of bioactive compounds. shRNAs that affect cellular sensitivity to a given compound can be identified by deep sequencing of shRNA-specific barcodes. We used multiplex barcode sequencing technology by adding sample-specific index tags to PCR primers during sequence library preparation, enabling parallel analysis of multiple samples.

The effects of increasing calcium channel blocker dose vs. adding a diuretic to treatment regimens for patients with uncontrolled hypertension.

In patients with insufficient blood pressure (BP) control, despite using a combination regimen containing an angiotensin receptor blocker and a calcium channel blocker (CCB), whether a greater dose of CCB or adding a diuretic is more effective at lowering BP remains unclear. We conducted a multicenter randomized clinical trial to compare the efficacy of switching from the daily administration of a single-pill fixed-dose combination of irbesartan (100 mg) and amlodipine (5 mg) to irbesartan (100 mg) with an increased dose of amlodipine (10 mg) (HD group, n=62) or irbesartan (100 mg) and amlodipine (5 mg) with 1 mg of indapamide (D group, n=63) in patients with poorly controlled hypertension. BP measured at home was monitored by a physician using a telemonitoring system.

Identification of Serratane Synthase Gene from the Fern Lycopodium clavatum.

Ferns are known to produce onoceroids including onoceranes and serratanes having unusual structures among triterpenes. From the fern Lycopodium clavatum, a novel onoceroid synthase gene was cloned that showed high sequence identity with a previously identified α-onocerin synthase. Functional analysis by coexpression with pre-α-onocerin synthase in yeast led to the production of tohogenol and serratenediol.

Increased cardiovascular risk of treated white coat and masked hypertension in patients with diabetes and chronic kidney disease: the HONEST Study.

The prognostic implications of treated white coat hypertension (WCH) and masked hypertension (MH) in patients with diabetes mellitus (DM) or chronic kidney disease (CKD) are not well documented. Using data from the HONEST study (n=21 591), we investigated the relationships between morning home systolic blood pressure (MHSBP) or clinic systolic blood pressure (CSBP) and cardiovascular (CV) risk in hypertensive patients with and without DM or CKD receiving olmesartan-based antihypertensive therapy. The study included 4426 DM patients and 4346 CKD patients at baseline who had 101 and 87 major CV events, respectively, during the follow-up.

A draft genome of the brown alga, Cladosiphon okamuranus, S-strain: a platform for future studies of 'mozuku' biology.

The brown alga, Cladosiphon okamuranus (Okinawa mozuku), is economically one of the most important edible seaweeds, and is cultivated for market primarily in Okinawa, Japan. C. okamuranus constitutes a significant source of fucoidan, which has various physiological and biological activities.

Home blood pressure and cardiovascular risk in treated hypertensive patients: the prognostic value of the first and second measurements and the difference between them in the HONEST study.

Hypertension guidelines recommend using the average of two home blood pressure (HBP) measurements obtained on one occasion to monitor blood pressure. We studied the prognostic value of the first and second measurements or their average value during the follow-up period, as well as the relationships among the difference between the first and second HBP measurements and the prognosis using data from the HONEST (HBP measurement with Olmesartan-Naive patients to Establish Standard Target blood pressure) study. During the mean 2.

Prognostic significance of on-treatment home and clinic blood pressure for predicting cardiovascular events in hypertensive patients in the HONEST study.

Objective: We investigated the prognostic significance of morning home SBP (MHSBP) and clinic SBP (CSBP) at baseline and during follow-up in on-treatment hypertensive patients.

Methods: In the Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure study, more than 20 000 Japanese hypertensive patients who started treatment with olmesartan were followed for cardiovascular events for 2 years. MHSBP and CSBP measured at baseline and during follow-up were compared in terms of the prognostic significance in predicting cardiovascular events.

Morning Home Blood Pressure Is a Strong Predictor of Coronary Artery Disease: The HONEST Study.

Background: Few studies have evaluated out-of-office blood pressure (BP) measurements as predictors of coronary artery disease (CAD) events.

Objectives: The aim of this study was to determine morning home blood pressure (HBP) as a predictor of CAD events.

Methods: Using data from the HONEST (Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure) study, we investigated the relationship between morning HBP and incidence of stroke and CAD events.

Highly Sprouting-Tolerant Wheat Grain Exhibits Extreme Dormancy and Cold Imbibition-Resistant Accumulation of Abscisic Acid.

Pre-harvest sprouting (PHS) of wheat (Triticum aestivum L.) grains induces hydrolyzing enzymes such as α-amylase, which considerably decreases wheat product quality. PHS occurs when cool and wet weather conditions before harvest break dormancy and induce grain germination.

Antihypertensive Efficacy of the Direct Renin Inhibitor Aliskiren as Add-on Therapy in Patients with Poorly Controlled Hypertension.

Objective: A direct renin inhibitor, aliskiren, has a longer stable antihypertensive effect compared with other renin-angiotensin-aldosterone system (RAAS) inhibitors.

Methods: This study was a 6-month, single-center, open trial conducted between December 2010 and November 2011 to assess the antihypertensive effect of adding aliskiren (300 mg) to the treatment of essential hypertension patients whose target blood pressure (BP) had not been achieved and to assess whether it was possible to reduce the amount of antihypertensive drugs used.

Results: The results showed an overall improvement in the target BP achievement rate of 60% for clinic BP and 52% for home BP measurements (75 cases total).