Sirtuin E is a fungal global transcriptional regulator that determines the transition from the primary growth to the stationary phase

In response to limited nutrients, fungal cells exit the primary growth phase, enter the stationary phase, and cease proliferation. Although fundamental to microbial physiology in many environments, the regulation of this transition is poorly understood but likely involves many transcriptional regulators. These may include the sirtuins, which deacetylate acetyllysine residues of histones and epigenetically regulate global transcription. Therefore, we investigated the role of a nuclear sirtuin, sirtuin E (SirE), from the ascomycete fungus Aspergillus nidulans. An A. nidulans strain with a disrupted sirE gene (SirEΔ) accumulated more acetylated histone H3 during the stationary growth phase when sirE was expressed at increased levels in the wild type. SirEΔ exhibited decreased mycelial autolysis, conidiophore development, sterigmatocystin biosynthesis, and production of extracellular hydrolases. Moreover, the transcription of the genes involved in these processes was also decreased, indicating that SirE is a histone deacetylase that up-regulates these activities in the stationary growth phase. Transcriptome analyses indicated that SirE repressed primary carbon and nitrogen metabolism and cell-wall synthesis. Chromatin immunoprecipitation demonstrated that SirE deacetylates acetylated Lys-9 residues in histone H3 at the gene promoters of α-1,3-glucan synthase (agsB), glycolytic phosphofructokinase (pfkA), and glyceraldehyde 3-phosphate (gpdA), indicating that SirE represses the expression of these primary metabolic genes. In summary, these results indicate that SirE facilitates the metabolic transition from the primary growth phase to the stationary phase. Because the observed gene expression profiles in stationary phase matched those resulting from carbon starvation, SirE appears to control this metabolic transition via a mechanism associated with the starvation response

Sirtuin A regulates secondary metabolite production by Aspergillus nidulans

Late-stage cultures of filamentous fungi under nutrient starvation produce valuable secondary metabolites such as pharmaceuticals and pigments, as well as deleterious mycotoxins, all of which have remarkable structural diversity and wide-spectrum bioactivity. The fungal mechanisms regulating the synthesis of many of these compounds are not fully understood, but sirtuin A (SirA) is a key factor that initiates production of the secondary metabolites, sterigmatocystin and penicillin G, by Aspergillus nidulans. Sirtuin is a ubiquitous NAD+-dependent histone deacetylase that converts euchromatin to heterochromatin and silences gene expression. In this study, we have investigated the transcriptome of a sirA gene disruptant (SirAΔ), and found that SirA concomitantly repressed the expression of gene clusters for synthesizing secondary metabolites and activated that of others. Extracts of SirAΔ cultures grown on solid agar and analyzed by HPLC indicated that SirA represses the production of austinol, dehydroaustinol and sterigmatocystin. These results indicated that SirA is a transcriptional regulator of fungal secondary metabolism

Local expression of Toll-like receptor 4 at the site of ruptured plaques in patients with acute myocardial infarction

Several reports suggest that a chronic inflammatory process plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. In a previous study, we found that TLR4 (Toll-like receptor 4) mediates the synthesis of cytokines in circulating monocytes of patients with AMI (acute myocardial infarction); however, it remains unclear whether TLRs are expressed at the site of the ruptured plaque in these patients. The aim of the present study was to determine whether TLR2 and TLR4 are expressed at the site of ruptured plaques in patients with AMI and to compare this with systemic levels. The study included 62 patients with AMI, 20 patients with SA (stable angina) and 32 subjects with a normal coronary angiogram (control). Local samples from the site of the ruptured plaque were taken from patients with AMI using aspiration catheterization. Systemic blood samples from the aorta were taken from patients with AMI and SA and controls. Systemic levels of TLR2 and TLR4 were higher in patients with AMI than in patients with SA and controls. In patients with AMI, local TLR4 levels were higher than systemic levels. There was no significant difference in TLR2 levels between local and systemic samples. TLR4 immunostaining was positive in infiltrating macrophages in ruptured plaque material. Cardiac events were observed in 16 patients with AMI at the time of the 6-month follow-up study. Local and systemic levels of TLR4 were higher in patients with AMI with cardiac events than in those without. These results indicate an increase in monocytic TLR4 expression not only in the systemic circulation, but also at the site of plaque rupture. In conclusion, expression of both systemic and local plaque TLR4 may be one of the mechanisms responsible for the pathogenesis of AMI

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

DEAD-Box Protein Ddx46 Is Required for the Development of the Digestive Organs and Brain in Zebrafish

Spatially and temporally controlled gene expression, including transcription, several mRNA processing steps, and the export of mature mRNA to the cytoplasm, is essential for developmental processes. It is well known that RNA helicases of the DExD/H-box protein family are involved in these gene expression processes, including transcription, pre-mRNA splicing, and rRNA biogenesis. Although one DExD/H-box protein, Prp5, a homologue of vertebrate Ddx46, has been shown to play important roles in pre-mRNA splicing in yeast, the in vivo function of Ddx46 remains to be fully elucidated in metazoans. In this study, we isolated zebrafish morendo (mor), a mutant that shows developmental defects in the digestive organs and brain, and found that it encodes Ddx46. The Ddx46 transcript is maternally supplied, and as development proceeds in zebrafish larvae, its ubiquitous expression gradually becomes restricted to those organs. The results of whole-mount in situ hybridization showed that the expression of various molecular markers in these organs is considerably reduced in the Ddx46 mutant. Furthermore, splicing status analysis with RT-PCR revealed unspliced forms of mRNAs in the digestive organ and brain tissues of the Ddx46 mutant, suggesting that Ddx46 may be required for pre-mRNA splicing during zebrafish development. Therefore, our results suggest a model in which zebrafish Ddx46 is required for the development of the digestive organs and brain, possibly through the control of pre-mRNA splicing

Current status of space gravitational wave antenna DECIGO and B-DECIGO

Deci-hertz Interferometer Gravitational Wave Observatory (DECIGO) is the future Japanese space mission with a frequency band of 0.1 Hz to 10 Hz. DECIGO aims at the detection of primordial gravitational waves, which could be produced during the inflationary period right after the birth of the universe. There are many other scientific objectives of DECIGO, including the direct measurement of the acceleration of the expansion of the universe, and reliable and accurate predictions of the timing and locations of neutron star/black hole binary coalescences. DECIGO consists of four clusters of observatories placed in the heliocentric orbit. Each cluster consists of three spacecraft, which form three Fabry-Perot Michelson interferometers with an arm length of 1,000 km. Three clusters of DECIGO will be placed far from each other, and the fourth cluster will be placed in the same position as one of the three clusters to obtain the correlation signals for the detection of the primordial gravitational waves. We plan to launch B-DECIGO, which is a scientific pathfinder of DECIGO, before DECIGO in the 2030s to demonstrate the technologies required for DECIGO, as well as to obtain fruitful scientific results to further expand the multi-messenger astronomy.Comment: 10 pages, 3 figure