The role of ribonucleases in regulating global mRNA levels in the model organism Thermus thermophilus HB8

BACKGROUND: RNA metabolism, including RNA synthesis and RNA degradation, is one of the most conserved biological systems and has been intensively studied; however, the degradation network of ribonucleases (RNases) and RNA substrates is not fully understood. RESULTS: The genome of the extreme thermophile, Thermus thermophilus HB8 includes 15 genes that encode RNases or putative RNases. Using DNA microarray analyses, we examined the effects of disruption of each RNase on mRNA abundance. Disruption of the genes encoding RNase J, RecJ-like protein and RNase P could not be isolated, indicating that these RNases are essential for cell viability. Disruption of the TTHA0252 gene, which was not previously considered to be involved in mRNA degradation, affected mRNA abundance, as did disruption of the putative RNases, YbeY and PhoH-like proteins, suggesting that they have RNase activity. The effects on mRNA abundance of disruption of several RNase genes were dependent on the phase of cell growth. Disruption of the RNase Y and RNase HII genes affected mRNA levels only during the log phase, whereas disruption of the PhoH-like gene affected mRNA levels only during the stationary phase. Moreover, disruption of the RNase R and PNPase genes had a greater impact on mRNA abundance during the stationary phase than the log phase, whereas the opposite was true for the TTHA0252 gene disruptant. Similar changes in mRNA levels were observed after disruption of YbeY or PhoH-like genes. The changes in mRNA levels in the bacterial Argonaute disruptant were similar to those in the RNase HI and RNase HII gene disruptants, suggesting that bacterial Argonaute is a functional homolog of RNase H. CONCLUSION: This study suggests that T. thermophilus HB8 has 13 functional RNases and that each RNase has a different function in the cell. The putative RNases, TTHA0252, YbeY and PhoH-like proteins, are suggested to have RNase activity and to be involved in mRNA degradation. In addition, PhoH-like and YbeY proteins may act cooperatively in the stationary phase. This study also suggests that endo-RNases function mainly during the log phase, whereas exo-RNases function mainly during the stationary phase. RNase HI and RNase HII may have similar substrate selectivity

ACTN1 Mutations Cause Congenital Macrothrombocytopenia

Congenital macrothrombocytopenia (CMTP) is a heterogeneous group of rare platelet disorders characterized by a congenital reduction of platelet counts and abnormally large platelets, for which CMTP-causing mutations are only found in approximately half the cases. We herein performed whole-exome sequencing and targeted Sanger sequencing to identify mutations that cause CMTP, in which a dominant mode of transmission had been suspected but for which no known responsible mutations have been documented. In 13 Japanese CMTP-affected pedigrees, we identified six (46%) affected by ACTN1 variants cosegregating with CMTP. In the entire cohort, ACNT1 variants accounted for 5.5% of the dominant forms of CMTP cases and represented the fourth most common cause in Japanese individuals. Individuals with ACTN1 variants presented with moderate macrothrombocytopenia with anisocytosis but were either asymptomatic or had only a modest bleeding tendency. ACTN1 encodes α-actinin-1, a member of the actin-crosslinking protein superfamily that participates in the organization of the cytoskeleton. In vitro transfection experiments in Chinese hamster ovary cells demonstrated that altered α-actinin-1 disrupted the normal actin-based cytoskeletal structure. Moreover, transduction of mouse fetal liver-derived megakaryocytes with disease-associated ACTN1 variants caused a disorganized actin-based cytoskeleton in megakaryocytes, resulting in the production of abnormally large proplatelet tips, which were reduced in number. Our findings provide an insight into the pathogenesis of CMTP

Percutaneous coronary intervention using new-generation drug-eluting stents versus coronary arterial bypass grafting in stable patients with multi-vessel coronary artery disease: From the CREDO-Kyoto PCI/CABG registry Cohort-3

AIMS: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease. METHODS AND RESULTS: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001). CONCLUSIONS: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD

千葉県君津市川谷地域に露出する中部更新統柿ノ木台層から産出する冷湧水化石群集: その時空分布と共産する自生炭酸塩

金沢大学国際基幹教育院 GS教育系冷湧水性群集が房総半島の中部更新統柿ノ木台層の陸棚相から産出する．群集は，化学合成二枚貝類から排他的になり，著しく13Cに枯渇した自生炭酸塩と共産することから，AOM（嫌気的メタン酸化）に依存していたと考えられる．自生炭酸塩は巣穴壁面と巣穴周囲の堆積物中に沈殿し，巣穴からスナモグリ類の爪化石と糞化石が産出することから，これらはスナモグリ類の巣穴であると考えられる．スナモグリ類はメタン生成帯まで巣穴を堀り，海水を巣穴深部へ供給し，AOMを活性化させることによって巣穴中の硫化水素イオン濃度を上昇させた．溶存酸素濃度が高い巣穴浅部では，硫黄酸化菌が繁茂し，スナモグリ類の食糧となった．巣穴深部では，浮遊する生物源炭酸塩などを核とした針状アラゴナイトが重力方向に沈下して炭酸塩ジオペタル状構造を形成し，巣穴周囲の堆積物中では，リン酸イオン濃度の上昇により高Mgカルサイトが，また硫酸イオンの枯渇によりドロマイトが沈殿した．Cold-seep-dependent molluscan assemblages occur in the outer-shelf facies of the middle Pleistocene Kakinokidai Formation of the Kazusa Group, a forearc basin-fill sequence on the Pacific side of central Japan, in strata corresponding to the interval 707.6-667.0 ka. The assemblages consist exclusively of chemosymbiotic bivalves (lucinids, thyasirids, and solemyids) and are associated with 13C-depleted authigenic carbonates (δ13C = −61.60‰ to −10.96‰ VPDB), which suggest that their main carbon source was anaerobic oxidation of methane (AOM). Authigenic carbonate precipitates are common on burrow walls (mainly acicular aragonite) and the surrounding sediments (mainly micritic high-Mg calcite and dolomite). The burrows are cylindrical, 1.5-3.0 cm in diameter, and >1 m long. Callianassid claws and the trace fossil Palaxius (probable callianassid fecal pellets) in the burrow carbonates suggest that the burrows were produced by sediment-dwelling callianassid decapods.\nWe propose the following formation mechanism of burrows and their related authigenic carbonates. Firstly, callianassids produced deep burrows, penetrating the AOM zone and reaching the methanogenic zone. Methane then seeped into the burrows and AOM occurred in its deeper parts, promoted by a supply of seawater via callianassid activity, resulting in an increase in the concentration of hydrogen sulfide ions. Thiobacteria flourished in the shallower parts of the burrows, which were enriched in dissolved oxygen, and provided a source of food for the callianassids. In the deeper parts of the burrows, acicular aragonite precipitated around suspended carbonate nuclei and sank to the bottoms of the burrows, forming geopetal-like carbonate structures. In the surrounding sediment, high-Mg calcite precipitated in response to an increase in the concentration of phosphate ions (due to the decomposition of organic matter), and dolomite precipitated in response to decreasing concentrations of sulfate ions (caused by active AOM)