Tsumura-Suzuki obese diabetic mice-derived hepatic tumors closely resemble human hepatocellular carcinomas in metabolism-related genes expression and bile acid accumulation

Background and aims Tsumura-Suzuki obese diabetic (TSOD) is a good model of metabolic syndrome showing typical lesions found in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and develops spontaneous hepatic tumors with a high frequency. Majority of the developing tumors overexpress glutamine synthetase (GS), which is used as a marker of hepatocellular carcinoma (HCC). The aim of this study is to assess the status of expression of metabolism-related genes and the level of bile acids in the TSOD mice-derived tumors and to determine the association with metabolic dysregulation between human HCC and TSOD mice-derived tumors. Methods GS-positive hepatic tumors or adjacent normal tissues from 71-week-old male TSOD mice were subjected to immunohistochemical staining (IHC), quantitative RT-PCR (qRT-PCR), quantitation of cholic acid and taurocolic acid. Results We found that downregulation of the rate-limiting enzyme for betaine synthesis (BADH), at both mRNA and protein levels in GS-positive TSOD mice-derived tumors. Furthermore, the bile acid receptor FXR and the bile acid excretion pump BSEP (Abcb11) were found to be downregulated, whereas BAAT and Akr1c14, involved in primary bile acid synthesis and bile acid conjugation, were found to be upregulated at mRNA level in GS-positive TSOD mice-derived tumors. BAAT and Akr1c14 was also overexpressed at protein levels. Total cholic acid was found to be increased in GS-positive TSOD mice-derived tumors. Conclusion Our results strongly support the significance of TSOD mice as a model of spontaneously developing HCC

Mass spectrometry imaging of the capsaicin localization in the capsicum fruits

We succeeded in performing mass spectrometry imaging (MSI) of the localization of capsaicin in cross-sections of the capsicum fruits at a resolution of 250 µm using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Post source decay of protonated capsaicin ion revealed structural information of the corresponding acid amide of vanillylamide and C9 chain fatty acid. MALDI-TOF-MSI confirmed that localization of capsaicin in the placenta is higher than that in the pericarp. In addition, it revealed no localization of capsaicin in seed and the higher localization of capsaicin at placenta surface compared with that in the internal region. A quantitative difference was detected between localizations of capsaicin at placenta, pericarp and seed in the capsicum fruits. This imaging approach is a promising technique for rapid quality evaluation general food as well as health food and identification of medicinal capsaicin in plant tissues

Localization Analysis of Natural Toxin of Solanum tuberosum L. via Mass Spectrometric Imaging

The use of mass spectrometry imaging (MSI) revealed the localization of alpha-solanine and alpha-chaconine as natural toxins for Potato (Solanum tuberosum L.). The content of Potato glycoalkaloids, alpha-solanine and alpha-chaconine, were quantitatively determined by high performance liquid chromatography (HPLC). Matrix assisted laser desorption/ionization-based tandem mass spectrometry (MS) could determine alpha-solanine and alpha-chaconine from raw potato extraction and section. After budbreak, alpha-solanine and alpha-chaconine were produced and localized at periderm and germ compared with that before budbreak. At germ region, these glycoalkaloids did not exist whole germ region but eccentrically localize at germ surface and central region. The amount of alpha-chaconine was twofold higher than alpha-solanine at periderm. At germ region, there was no difference between these toxins

Ammonium regulates the development of pine roots through hormonal crosstalk and differential expression of transcription factors in the apex

Ammonium is a prominent source of inorganic nitrogen for plant nutrition, but excessive amounts can be toxic for many species. However, most conifers are tolerant to ammonium, a relevant physiological feature of this ancient evolutionary lineage. For a better understanding of the molecular basis of this trait, ammonium‐induced changes in the transcriptome of maritime pine (Pinus pinaster Ait.) root apex have been determined by laser capture microdissection and RNA sequencing. Ammonium promoted changes in the transcriptional profiles of multiple transcription factors, such as SHORT‐ROOT, and phytohormone‐related transcripts, such as ACO, involved in the development of the root meristem. Nano‐PALDI‐MSI and transcriptomic analyses showed that the distributions of IAA and CKs were altered in the root apex in response to ammonium nutrition. Taken together, the data suggest that this early response is involved in the increased lateral root branching and principal root growth, which characterize the long‐term response to ammonium supply in pine. All these results suggest that ammonium induces changes in the root system architecture through the IAA‐CK‐ET phytohormone crosstalk and transcriptional regulation.This study was funded by Spanish Ministerio de Ciencia e Innovación, grant numbers BIO2015‐73512‐JIN MINECO/AEI/FEDER, UE; RTI2018‐094041‐B‐I00 and EQC2018‐004346‐P. Funding for open access charge: Universidad de Málaga/CBUA. FO was supported by grants from the Universidad de Málaga (Programa Operativo de Empleo Juvenil vía SNJG, UMAJI11, FEDER, FSE, Junta de Andalucía) and BIO‐114, Junta de Andalucí

Weak quasistatic magnetism in the frustrated Kondo lattice Pr_2Ir_2O_7

Muon spin relaxation experiments have been performed in the pyrochlore iridate Pr_2Ir_2O_7 for temperatures in the range 0.025-250 K. Kubo-Toyabe relaxation functions are observed up to > 200 K, indicating static magnetism over this temperature range. The T -> 0 static muon spin relaxation rate Delta(0) ~ 8 mus^-1 implies a weak quasistatic moment (~0.1 mu_B). The temperature dependence of Delta is highly non-mean-field-like, decreasing smoothly by orders of magnitude but remaining nonzero below ~150 K. The data rule out ordering of the full Pr^3+ CEF ground-state moment (3.0 mu_B) down to 0.025 K. The weak static magnetism is most likely due to hyperfine-enhanced ^141Pr nuclear magnetism. The dynamic relaxation rate lambda increases markedly below ~20 K, probably due to slowing down of spin fluctuations in the spin-liquid state. At low temperatures lambda is strong and temperature-independent, indicative of a high density of low-lying spin excitations as is common in frustrated antiferromagnets.Comment: 4 pages, 3 figures, to appear in Proc. 11th Int. Conf. on Muon Spin Rotation, Relaxation and Resonance (muSR2008

Loss of alpha-tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function.

Microtubules function as molecular tracks along which motor proteins transport a variety of cargo to discrete destinations within the cell. The carboxyl termini of alpha- and beta-tubulin can undergo different posttranslational modifications, including polyglutamylation, which is particularly abundant within the mammalian nervous system. Thus, this modification could serve as a molecular "traffic sign" for motor proteins in neuronal cells. To investigate whether polyglutamylated alpha-tubulin could perform this function, we analyzed ROSA22 mice that lack functional PGs1, a subunit of alpha-tubulin-selective polyglutamylase. In wild-type mice, polyglutamylated alpha-tubulin is abundant in both axonal and dendritic neurites. ROSA22 mutants display a striking loss of polyglutamylated alpha-tubulin within neurons, including their neurites, which is associated with decreased binding affinity of certain structural microtubule-associated proteins and motor proteins, including kinesins, to microtubules purified from ROSA22-mutant brain. Of the kinesins examined, KIF1A, a subfamily of kinesin-3, was less abundant in neurites from ROSA22 mutants in vitro and in vivo, whereas the distribution of KIF3A (kinesin-2) and KIF5 (kinesin-1) appeared unaltered. The density of synaptic vesicles, a cargo of KIF1A, was decreased in synaptic terminals in the CA1 region of hippocampus in ROSA22 mutants. Consistent with this finding, ROSA22 mutants displayed more rapid depletion of synaptic vesicles than wild-type littermates after high-frequency stimulation. These data provide evidence for a role of polyglutamylation of alpha-tubulin in vivo, as a molecular traffic sign for targeting of KIF1 kinesin required for continuous synaptic transmission

Challenges and Prospects for EMI in Asian Countries: A Report from Universities in Japan and Taiwan

本論は、英語を媒介とする専門教育（EMI）について、関西大学と東呉大学（台湾）が共同で行った実践および研究に関する論考である。EMIが盛んな欧州の事情とは異なり、言語的にも文化的にも違いが大きい日本、台湾、あるいはアジアにおいて、授業を英語で行うには克服すべき問題も多い。EMI実践から顕著に見えてくる、日台双方の学生・教員に共通するのは、①学生の英語運用能力、②運用能力の格差に起因する専門分野での理解、③授業・学習スタイルの相違、といった問題である。EMI導入の契機として、大学の国際化に伴う英語での学位取得という壮大な目標も巷間には聞かれるが、そもそも高等教育の質保証という観点から日台、あるいはアジアのEMIが目指すべきものは何か。現場のレベルで問い直すとともに、EMI実践・研究の展望に触れる。本取組は、2017年度関西大学教育研究高度化促進費において、課題「専門科目を英語で教育する方法についての国際共同研究」として促進費を受け、その成果を公表するものである