CCL5 protein level: influence on breast cancer staging and lymph nodes commitment

Molecular Biology Reports - Many tumor cells express chemokines and chemokine receptors, and these molecules can contribute to distinct modes of metastasis processes. It is known that they play a...     

Identification of the role of bone morphogenetic protein (BMP) and transforming growth factor‐β (TGF‐β) signaling in the trajectory of serotonergic differentiation in a rapid assay in mouse embryonic stem cells in vitro

The mechanism by which extracellular molecules control serotonergic cell fate remains elusive. Recently, we showed that noggin, which inactivates bone morphogenetic proteins (BMPs), induces serotonergic differentiation of mouse embryonic (ES) and induced pluripotent stem cells with coordinated gene expression along the serotonergic lineage. Here, we created a rapid assay for serotonergic induction by generating knock‐in ES cells expressing a naturally secreted Gaussia luciferase driven by the enhancer of Pet‐1/Fev, a landmark of serotonergic differentiation. Using these cells, we performed candidate‐based screening and identified BMP type I receptor kinase inhibitors LDN‐193189 and DMH1 as activators of luciferase. LDN‐193189 induced ES cells to express the genes encoding Pet‐1, tryptophan hydroxylase 2, and the serotonin transporter, and increased serotonin release without altering dopamine release. In contrast, TGF‐β receptor inhibitor SB‐431542 selectively inhibited serotonergic differentiation, without changing overall neuronal differentiation. LDN‐193189 inhibited expression of the BMP signaling target gene Id, and induced the TGF‐β target gene Lefty, whereas the opposite effect was observed with SB‐431542. This study thus provides a new tool to investigate serotonergic differentiation and suggests that inhibition of BMP type I receptors and concomitant activation of TGF‐β receptor signaling are implicated in serotonergic differentiation.

     

Survival of Bactrocera latifrons (Diptera: Tephritidae) adults under constant and fluctuating low temperatures

Bactrocera latifrons (Hendel) is believed to have originated in Southeast Asia but has invaded Hawaii and most recently East Africa. This insect has also been recorded on Okinawa Island, the far south of Kyushu Island, Japan. To assess the overwintering ability of B. latifrons adults, survival at constant temperatures (8, 10, 12, 14, 15 °C) and under fluctuating thermal regimes (FTRs) was investigated. At 14 or 15 °C, more than 30 % of females survived for 90 days. Time required to kill 95 % of B. latifrons at 8 °C was estimated to be 13 days; at 10 °C, 29 days; and at 12 °C, 38 days for females, and 8, 17, and 24 days at the same above temperatures, respectively, for males, suggesting low cold tolerance of this species. The results show that females survive cold temperatures better than males. Under an FTR of 11 °C (22 h)/20 °C (2 h) (average 11.8 °C) survival of females drastically increased compared to that at a constant temperature of 12 °C, whereas the survival of males increased slightly. Survival under FTRs indicates that adult B. latifrons may not overwinter in the north of Tanegashima Island, located 30 km south of Kyushu Island, Japan.     

A unique mechanism of curcumin inhibition on F1 ATPase

ATP synthase (F-ATPase) function depends upon catalytic and rotation cycles of the F₁ sector. Previously, we found that F₁ ATPase activity is inhibited by the dietary polyphenols, curcumin, quercetin, and piceatannol, but that the inhibitory kinetics of curcumin differs from that of the other two polyphenols (Sekiya et al., 2012, 2014). In the present study, we analyzed Escherichia coli F₁ ATPase rotational catalysis to identify differences in the inhibitory mechanism of curcumin versus quercetin and piceatannol. These compounds did not affect the 120° rotation step for ATP binding and ADP release, though they significantly increased the catalytic dwell duration for ATP hydrolysis. Analysis of wild-type F₁ and a mutant lacking part of the piceatannol binding site (γΔ277–286) indicates that curcumin binds to F₁ differently from piceatannol and quercetin. The unique inhibitory mechanism of curcumin is also suggested from its effect on F₁ mutants with defective β–γ subunit interactions (γMet23 to Lys) or β conformational changes (βSer174 to Phe). These results confirm that smooth interaction between each β subunit and entire γ subunit in F₁ is pertinent for rotational catalysis.     

Elastic rotation of Escherichia coli FOF1 having ε subunit fused with cytochrome b562 or flavodoxin reductase

Intra-molecular rotation of F_OF₁ ATP synthase enables cooperative synthesis and hydrolysis of ATP. In this study, using a small gold bead probe, we observed fast rotation close to the real rate that would be exhibited without probes. Using this experimental system, we tested the rotation of F_OF₁ with the ε subunit connected to a globular protein [cytochrome b₅₆₂ (ε-Cyt) or flavodoxin reductase (ε-FlavR)], which is apparently larger than the space between the central and the peripheral stalks. The enzymes containing ε-Cyt and ε-FlavR showed continual rotations with average rates of 185 and 148 rps, respectively, similar to the wild type (172 rps). However, the enzymes with ε-Cyt or ε-FlavR showed a reduced proton transport. These results indicate that the intra-molecular rotation is elastic but proton transport requires more strict subunit/subunit interaction.     

Radioactive contamination of aquatic insects in a stream impacted by the Fukushima nuclear power plant accident

The Fukushima Daiichi Nuclear Power Plant accident emitted radioactive substances into the environment, contaminating a diverse range of organisms. Stream algae, litter, sand substrate, aquatic insects and fishes are among the organisms that have been impacted. Radioactive Cs contaminations in the litter and sand substrate were elevated where the atmospheric dose rate in the air was high. Radioactive Cs contaminations in algae and aquatic insects varied irregularly; nevertheless, radioactive Cs contaminations in aquatic insects in pools were consistently higher than those in stream riffles. Contamination by the radioactive Cs differed by species, location and stream velocity. This study was undertaken in a limited number of samples and sites, with more extensive studies planned to fully determine the impact of radionuclides on aquatic ecosystems.