Sex pheromone production in the silkworm, Bombyx mori, is mediated by store-operated Ca2+ channels

In most female moths, pheromone biosynthesis activating neuropeptide (PBAN) regulates sex pheromone production by stimulating an influx of extracellular Ca(2+). Little is known about the plasma membrane channel or how the PBAN stimulus is communicated to the channel. Fluorescent Ca(2+) imaging techniques confirmed PBAN-induced Ca(2+) influx in the silkworm, Bombyx mori, and showed that the PBAN response is reduced with repeated stimulation. Compounds known to impact Ca(2+) signaling were examined for their effects on sex pheromone production. These experiments demonstrated that the PBAN signal is likely mediated by a store-operated channel (SOC). SOC blockers, SKF-96365 and 2-aminoethoxydiphenyl borate, abolished sex pheromone production, as did flufenamic acid, a blocker of transient receptor potential (TRP) channels. Thapsigargin mimicked the pheromonotropic effects of PBAN. Similar results were seen when PBAN-induced lipase activity was assayed. Conversely, 1-oleoyl-2-acetyl-sn-glycerol and arachidonic acid, activators of diacylglycerol-dependent Ca(2+) channels, had no effect on bombykol production.     

Non-fucosylated therapeutic antibodies: the next generation of therapeutic antibodies

Therapeutic antibody IgG1 has two N-linked oligosaccharide chains bound to the Fc region. The oligosaccharides are of the complex biantennary type, composed of a trimannosyl core structure with the presence or absence of core fucose, bisecting N-acetylglucosamine (GlcNAc), galactose, and terminal sialic acid, which gives rise to structural heterogeneity. Both human serum IgG and therapeutic antibodies are well known to be heavily fucosylated. Recently, antibody-dependent cellular cytotoxicity (ADCC), a lytic attack on antibody-targeted cells, has been found to be one of the critical effector functions responsible for the clinical efficacy of therapeutic antibodies such as anti-CD20 IgG1 rituximab (Rituxan^®) and anti-Her2/neu IgG1 trastuzumab (Herceptin^®). ADCC is triggered upon the binding of lymphocyte receptors (FcγRs) to the antibody Fc region. The activity is dependent on the amount of fucose attached to the innermost GlcNAc of N-linked Fc oligosaccharide via an α-1,6-linkage, and is dramatically enhanced by a reduction in fucose. Non-fucosylated therapeutic antibodies show more potent efficacy than their fucosylated counterparts both in vitro and in vivo, and are not likely to be immunogenic because their carbohydrate structures are a normal component of natural human serum IgG. Thus, the application of non-fucosylated antibodies is expected to be a powerful and elegant approach to the design of the next generation therapeutic antibodies with improved efficacy. In this review, we discuss the importance of the oligosaccharides attached to the Fc region of therapeutic antibodies, especially regarding the inhibitory effect of fucosylated therapeutic antibodies on the efficacy of non-fucosylated counterparts in one medical agent. The impact of completely non-fucosylated therapeutic antibodies on therapeutic fields will be also discussed.     

Association of cathepsin E with tumor growth arrest through angiogenesis inhibition and enhanced immune responses

Cathepsin E (CE) is an intracellular aspartic proteinase implicated in various physiological and pathological processes, yet its actual roles in vivo remain elusive. To assess the physiological significance of CE expression in tumor cells, human CE was stably expressed in human prostate carcinoma ALVA101 cells expressing very little CE activity. Tumor growth in nude mice with xenografted ALVA101/hCE cells was slower than with control ALVA101/mock cells. Angiogenesis antibody array and ELISA assay showed that this was partly due to the increased expression of some antiangiogenic molecules including interleukin 12 and endostatin in tumors induced by CE expression. In vitro studies also demonstrated that, among the cathepsins tested, CE most efficiently generated endostatin from the non-collagenous fragment of human collagen XVIII at mild acidic pH. Histological examination revealed that tumors formed by ALVA101/hCE cells were partitioned by well-developed membranous structures and covered with thickened, well-stratified hypodermal tissues. In addition, both the number and extent of activation of tumor-infiltrating macrophages were more profound in ALVA101/hCE compared to ALVA101/mock tumors. The chemotactic response of macrophages to ALVA101/hCE cells was also higher than that to ALVA/mock cells. These results thus indicate that CE expression in tumor cells induces tumor growth arrest via inhibition of angiogenesis and enhanced immune responses.     

Temporally explicit abiotic depletion potential (TADP) for mineral resource use based on future demand projections

Purpose

Assessing the potential impacts (characterization) of mineral resource use in life cycle impact assessment (LCIA) has long been debated. One of the most crucial challenges in the characterization models for mineral resource use is the consideration of the changing demand and availability of in-use stocks in the future, which is relevant to the global population and economy growth as well as the increasing low-carbon technologies. We propose an extended characterization model to assess the potential impacts for arbitrary time horizons, considering future demand changes and the availability of in-use stock: temporally explicit abiotic depletion potential (TADP).

Methods

The TADP was developed based on abiotic depletion potential (ADP), which is a widely used characterization model for mineral resource use. While the ADP assesses the potential impacts of mineral resource use based on a natural stock estimate and the current extraction rate, the TADP adopts an average extraction rate for arbitrary time horizons. The average extraction rate was estimated using material flow analysis considering future demand changes and recycling under the five shared socioeconomic pathways (SSPs). TADPs were calculated for six common metals: aluminum, copper, iron, lead, nickel, and zinc.

Results and discussion

As a result of calculating TADPs for the term by 2050 (TADP₂₀₅₀), compared to iron, all other metals showed larger values of characterization factors for all SSPs than the original ADPs. The TADP₂₀₅₀ of copper exhibited the largest difference with ADP among the six metals (approximately 1.9 times), which is mainly attributed to future demand growth. On the other hand, for the longer time perspective, the TADP₂₁₀₀ of lead and zinc exhibited larger differences with ADP than copper (approximately 2.8 times for zinc), which is mainly due to a relatively shorter lifetime for lead and a lower recycling rate for zinc. This suggests that the relative significance of the characterization factors of metals varies depending on the temporal perspective.

Conclusions

With the proposed characterization model, the potential impacts of mineral resource use can be assessed reflecting future situations for the selected time horizons. The results demonstrate that the consideration of future situations greatly influences the relative significance of the potential impacts of using different mineral resources in the results of LCIA studies. By expanding the coverage of mineral resources and future scenario analysis to other relevant factors, the TADP model can improve the robustness of the assessment and further support decision-making towards sustainable resource management.

     

Fabrication of stable antibody-modified field effect transistors using electrical activation of Schiff base cross-linkages for tumor marker detection

In this paper, we present a method of fabricating a rigid antibody-immobilized surface using electric activation of a glutaraldehyde (GA)-modified aminopropylsilyl surface for stable antibody-modified field effect transistors (FETs). Electric activation of the GA-modified gate surface of the FET reduces Schiff bases, which are easily hydrolyzed and collapsed, formed between GA and 3-aminopropyltriethoxysilane, resulting in preventing the immobilized antibodies from desorbing from the surface. The lack of Raman peaks that could be assigned to a Schiff base after the electrical activation of the GA-modified surface indicated that the electric activation had reduced the Schiff base. The use of the antibody-modified FETs has three advantages for the detection of antigens: increased sensitivity, distinct recognition ability, and improved reproducibility. A tumor marker, alpha-fetoprotein (AFP), was quantitatively detected up to a concentration of 10 ng/mL using the antibody-modified FET. The detection ability of the FET accomplished a cutoff value of hepatic cancer. The quantitative detection of AFP in a solution with contaminating proteins was also demonstrated. This electric activation method is applicable to other antibody-modified FETs.     

Identification of novel nuclear protein interactions with the N-terminal part of filamin A

Since certain missense mutations in the N-terminal part of filamin A (FLNA) cause inherited skeletal malformation, we screened for proteins that bind to this part of FLNA. We identified two nuclear proteins that are specifically associated with the N-terminal region of FLNA. This suggests more extensive nuclear function of filamin than expected.     

A proposal of the method of deer density estimate without fecal decomposition rate: a case study of fecal accumulation rate technique in Japan

The accuracy of estimating deer density using the fecal pellet count method is greatly limited by variability of the fecal decomposition rate. The fecal accumulation rate technique can avoid the issue of decomposition rate. However, the precision of this technique is not clear when the decomposition rate is relatively high, such as in Japanese forests. We estimated deer population densities on Yakushima Island by the fecal accumulation rate technique and compared them between seasons. The estimated densities were similar to reported estimates, and did not differ seasonally, in accord with reports that deer on Yakushima do not migrate seasonally. Thus, we conclude that the fecal accumulation rate technique is applicable in Japanese forests.     

Effect of alcohol drinking and cigarette smoking on neutrophil functions in adults

In recent years, the effects of smoking and excessive alcohol consumption on immune function have been studied, due to a high prevalence of infection or cancer in heavy drinkers, and the combination of smoking and drinking was considered to be a carcinogenic risk. However, the effect of smoking and drinking on systemic immune function has yet to be clearly understood. In this study, we investigated neutrophil functions (reactive oxygen species (ROS) productive activity, phagocytic ability and serum opsonic activity) and their relationship with alcohol consumption or amount of smoking. In total there were 731 male and female adult subjects who participated in the Iwaki Health Promotion Project in 2005. Multiple regression analysis showed a trend of increased ROS production in male subjects and a statistically significant decrease was observed in phagocytic activity caused by smoking in female subjects. In other words, oxidative stress caused by smoking in male subjects may be involved in ROS production from neutrophils. Decreased phagocytic activity of neutrophils caused by smoking suggests that host defense functions were impaired in female subjects. A relationship between neutrophil functions and the amount of alcohol consumption was not observed. Copyright © 2011 John Wiley & Sons, Ltd.