Arm protein lost in epithelial cancers, on chromosome X (ALEX; also known as armadillo repeat containing, X-linked (ARMCX)) is a novel subgroup within the armadillo (ARM) family which has several ARM repeat domain. The biological function of classical ARM family members such as β-catenin is well understood, but that of the ALEX/ARMCX family members is largely unknown. Here we evaluate the effects of ALEX1 overexpression on in vitro colony formation ability and expression of ALEX1 mRNA in human colorectal tumor. Overexpression of ALEX1 suppressed the anchorage-dependent and -independent colony formation of human colorectal carcinoma cell lines by the study of stable clones of HCT116 cells expressing ALEX1 protein. Bisulfite genomic sequencing revealed that the promoter region of ALEX1 gene was highly methylated in both HCT116 and SW480 cells in comparison with PANC-1 and MCF-7 cells which express endogenous ALEX1 mRNA, indicating the capability of promoter methylation to silence ALEX1 gene in HCT116 and SW480 cells. Current our findings suggest that overexpression of ALEX1 play a negative role in human colorectal tumorigenesis.(171 words).

The divalent metal transporter 1 (DMT1) is essential for cellular uptake of iron, mediating iron absorption across the duodenal brush border membrane. We have previously shown that with iron feeding DMT1 in the brush border membrane undergoes endocytosis into the subapical compartment of enterocytes. To understand the mechanisms of iron induced endocytosis of DMT1, we used the yeast two-hybrid system to find proteins that interact with DMT1 and isolated from a rat duodenal cDNA library a protein that interacts specifically with the IRE containing isoform of DMT1 [DMT1 (IRE)]. The protein (Genbank AY336075) is 97.5 % identical with PAP7, a protein that interacts with the peripheral benzodiazepine receptor. PAP7 is ubiquitously expressed in the rat and in multiple cell lines with consensus sequences including a nuclear localization signal and a Golgi dynamic domain. PAP7, expressed on the brush border of rat duodenum, co-purified with DMT1 in brush border membrane vesicles, and following iron feeding, was internalized in parallel with the internalization of DMT1. To determine if PAP7 plays a role in cellular iron metabolism, we down regulated PAP7 expression in K562 cells with si RNA. Following the decrease in PAP7 protein DMT1 (IRE) protein but not mRNA was significantly down-regulated but without effect on DMT1 (non IRE), TfR1, or ferritin expression. Lowered levels of PAP7 resulted also in decreased cell proliferation and G1 cell cycle arrest. These data are consistent with PAP7 interacting with DMT1 (IRE) and regulating DMT1 (IRE) expression in K562 cells by modulating expression of DMT1 (IRE) protein.

Gerodontology 2012; doi: 10.1111/j.1741-2358.2011.00615.x Maximal voluntary tongue pressure is decreased in Japanese frail elderly persons Background and objective:  To quantitatively estimate tongue function, we developed a handy device for intraoral pressure measurement. The objective of this study was to assess maximum voluntary tongue pressure (MVTP) in Japanese frail elderly persons receiving nursing care services. Materials and methods:  The study included 42 men and 87 women, aged 58-100 years. To record MVTP, the participants were asked to compress the balloon (diameter: 18 mm) of the disposable intraoral pressure probe onto their palates for 7 s using the maximum voluntary effort of the tongue. Pressures were recorded three times at 1 min intervals. Results:  Maximum voluntary tongue pressure was successfully measured in 111 persons. Mean (standard deviation) MVTP was 18 (12) kPa, with a range of 0-63 kPa. The remaining 18 persons could not accurately follow our instructions and MVTP could not be measured. Conclusion:  In comparison with the reported standard value using the same device, the frail elderly persons included in our study were found to exert less MVTP than healthy dentate individuals. These results suggest the need for proper quantitative evaluation of oral function, including tongue capacity, at nursing care facilities.

The purpose of this study was to evaluate preoperative CT-derived bone densities in Hounsfield units (HU) at implant sites that acquired primary stability, and to compare these values to the optimal bone densities proposed in the literature. Fifty-one patients, 18 males (37 implant sites) and 33 females (67 implant sites) between 2003 and 2010 were assessed. CT data for different jaw sections, regions, and operating procedures were compared using the Kruskal-Wallis test and Scheffe's test for multiple comparisons (P < 0.05). The mean bone density in the maxilla was significantly lower than that in the mandible (P < 0.05); the mean bone densities in the 4 jaw regions decreased in the following order: anterior mandible > anterior maxilla > posterior mandible > posterior maxilla. The bone densities assessed by HU fell into the range of optimal bone densities associated with acquired primary implant stability proposed in the literature.

Multiwalled carbon nanotubes (MWCNTs) have the potential for widespread applications in engineering and materials science. However, because of their needle-like shape and high durability, concerns have been raised that MWCNTs may induce asbestos-like pathogenicity. Although recent studies have demonstrated that MWCNTs induce various types of reactivities, the physicochemical features of MWCNTs that determine their cytotoxicity and carcinogenicity in mesothelial cells remain unclear. Here, we showed that the deleterious effects of nonfunctionalized MWCNTs on human mesothelial cells were associated with their diameter-dependent piercing of the cell membrane. Thin MWCNTs (diameter ∼ 50 nm) with high crystallinity showed mesothelial cell membrane piercing and cytotoxicity in vitro and subsequent inflammogenicity and mesotheliomagenicity in vivo. In contrast, thick (diameter ∼ 150 nm) or tangled (diameter ∼ 2-20 nm) MWCNTs were less toxic, inflammogenic, and carcinogenic. Thin and thick MWCNTs similarly affected macrophages. Mesotheliomas induced by MWCNTs shared homozygous deletion of Cdkn2a/2b tumor suppressor genes, similar to mesotheliomas induced by asbestos. Thus, we propose that different degrees of direct mesothelial injury by thin and thick MWCNTs are responsible for the extent of inflammogenicity and carcinogenicity. This work suggests that control of the diameter of MWCNTs could reduce the potential hazard to human health.

Excessive intake of dietary salt (sodium chloride) may increase the risk of chronic diseases. Accordingly, various strategies to reduce salt intake have been conducted. This study aimed to investigate whether a salty-congruent odor can enhance saltiness on the basis of psychophysical (Experiment 1) and neuroanatomical levels (Experiment 2). In Experiment 1, after receiving one of six stimulus conditions: three odor conditions (odorless air, congruent, or incongruent odor) by two concentrations (low or high) of either salty or sweet taste solution, participants were asked to rate taste intensity and pleasantness. In Experiment 2, participants received the same stimuli during the functional magnetic resonance imaging scan. In Experiment 1, compared with an incongruent odor and/or odorless air, a congruent odor enhanced not only taste intensity but also either pleasantness of sweetness or unpleasantness of saltiness. In Experiment 2, a salty-congruent combination of odor and taste produced significantly higher neuronal activations in brain regions associated with odor-taste integration (e.g., insula, frontal operculum, anterior cingulate cortex, and orbitofrontal cortex) than an incongruent combination and/or odorless air with taste solution. In addition, the congruent odor-induced saltiness enhancement was more pronounced in the low-concentrated tastant than in the high-concentrated one. In conclusion, this study demonstrates the congruent odor-induced saltiness enhancement on the basis of psychophysical and neuroanatomical results. These findings support an alternative strategy to reduce excessive salt intake by adding salty-congruent aroma to sodium reduced food. However, there are open questions regarding the salty-congruent odor-induced taste unpleasantness. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.

Restriction landmark genome scanning (RLGS) method is a high-resolution two-dimensional electrophoresis system for analyses of the whole genome DNA which is including methylation status. It has been used for cloning genes of model animals and human genomes, detection of imprinted genes, and genome-wide methylation research in cancer. The conventional RLGS detected both polymorphism and methylated NotI sites between samples. Here, we have developed improved RLGS method with isoschizomer restriction enzymes such as MspI and HpaII to specifically detect methylated sites, using differential sensitivity of the restriction enzymes to methylated sequences. Recently, by using the genome database information, the RLGS spot sites were efficiently identified by this improved method. Then, genome methylation sites of Arabidopsis were mapped, and a unique inheritance was detected in methylated gene in rice. Now, epigenetic research becomes easy with the improved RLGS and it also can be applied for animal genome. Therefore, RLGS method is useful to explore for novel epigenetic phenomenon.

Asbestos is a potent carcinogen associated with increased risks of malignant mesothelioma and lung cancer in humans. Though the mechanism of carcinogenesis remains elusive, the physicochemical characteristics of asbestos play a role in the progression of asbestos-induced diseases. Among these characteristics, a high capacity to adsorb and accommodate biomolecules on its abundant surface area has been linked to cellular and genetic toxicity. Several previous studies identified asbestos-interacting proteins. Here, by the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS), we systematically identified proteins from various lysates that adsorbed to the surface of commercially used asbestos and classified them into the following groups: chromatin/nucleotide/RNA-binding proteins, ribosomal proteins, cytoprotective proteins, cytoskeleton-associated proteins, histones and hemoglobin. The surfaces of crocidolite and amosite, two iron-rich types of asbestos, caused more protein scissions and oxidative modifications than that of chrysotile by in situ generated 4-hydroxy-2-nonenal. On the other hand, we confirmed the intense hemolytic activity of chrysotile and found that hemoglobin attached to chrysotile, but not silica, can work as a catalyst to induce oxidative DNA damage. This process generates 8-hydroxy-2'-deoxyguanosine and thus corroborates the involvement of iron in the carcinogenicity of chrysotile. This evidence demonstrates that all three types of asbestos adsorb DNA and specific proteins, providing a niche for oxidative modification via catalytic iron. Therefore, considering the affinity of asbestos for histones/DNA and the internalization of asbestos into mesothelial cells, our results suggest a novel hypothetical mechanism causing genetic alterations during asbestos-induced carcinogenesis.