A Twist-like bHLH gene is a downstream factor of an endogenous FGF and determines mesenchymal fate in the ascidian embryos

Ascidian larvae develop mesenchyme cells in their trunk. A fibroblast growth factor (FGF9/16/20) is essential and sufficient for induction of the mesenchyme in Ciona savignyi. We have identified two basic helix-loop-helix (bHLH) genes named Twist-like1 and Twist-like2 as downstream factors of this FGF. These two genes are phylogenetically closely related to each other, and were expressed specifically in the mesenchymal cells after the 110-cell stage. Gene-knockdown experiments using a specific morpholino oligonucleotide demonstrated that Twist-like1 plays an essential role in determination of the mesenchyme and that Twist-like2 is a downstream factor of Twist-like1. In addition, both overexpression and misexpression of Twist-like1 converts non-mesenchymal cells to mesenchymal cells. We also demonstrate that the upstream regulatory mechanisms of Twist-like1 are different between B-line mesenchymal cells and the A-line mesenchymal cells called `trunk lateral cells'. FGF9/16/20 is required for the expression of Twist-like1 in B-line mesenchymal precursor cells, whereas FGF, FoxD and another novel bHLH factor called NoTrlc are required for Twist-like1 to be expressed in the A-line mesenchymal precursor cells. Therefore, two different but partially overlapping mechanisms are required for the expression of Twist-like1 in the mesenchymal precursors, which triggers the differentiation of the mesenchyme in Ciona embryos

Development of Morphological Diversity of Dendrites in Drosophila by the BTB-Zinc Finger Protein Abrupt

Morphological diversity of dendrites contributes to specialized functions of individual neurons. In the present study, we examined the molecular basis that generates distinct morphological classes of Drosophila dendritic arborization (da) neurons. da neurons are classified into classes I to IV in order of increasing territory size and/or branching complexity. We found that Abrupt (Ab), a BTB-zinc finger protein, is expressed selectively in class I cells. Misexpression of ab in neurons of other classes directed them to take the appearance of cells with smaller and/or less elaborated arbors. Loss of ab functions in class I neurons resulted in malformation of their typical comb-like arbor patterns and generation of supernumerary branch terminals. Together with the results of monitoring dendritic dynamics of ab-misexpressing cells or ab mutant ones, all of the data suggested that Ab endows characteristics of dendritic morphogenesis of the class I neurons

Visceral-to-subcutaneous fat ratio is a possible prognostic factor for type 1 endometrial cancer

[Background] Associations have been observed between obesity defined by the body mass index (BMI) and the incidence of endometrial cancer. However, the impact of obesity on the prognosis of endometrial cancer is not yet clear. Recently, visceral fat has been considered to have a greater impact on malignant disease in obese patients than subcutaneous fat. In this study, we investigated the association between prognostic factors of type 1 and type 2 endometrial cancer and obesity parameters. [Methods] The impacts of clinical factors on the progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively in 145 primary endometrial cancer patients. The factors included age, BMI, pathological findings, Federation of Gynecology and Obstetrics (FIGO) stage, status of lymph node metastasis, and the amounts of visceral and subcutaneous fat obtained from computed tomography (CT) data. [Results] Only the visceral-to-subcutaneous fat ratio (V/S ratio) (cutoff value 0.5) corresponded to a significant difference in OS and PFS in type 1 endometrial cancer (p = 0.0080, p = 0.0053) according to the results of log-rank tests of Kaplan–Meier curves. The COX regression univariate analysis revealed that only the V/S ratio was a significant prognostic factor for PFS, but not OS (p = 0.033 and p = 0.270, respectively). [Conclusion] A V/S ratio > 0.5 is a possible factor for poor prognosis in type 1 endometrial cancer. Further research is needed to investigate the preventive and therapeutic effects of reducing visceral fat on the prognosis of this type of cancer

Radioprotection by p53 Regulatory Agents

Radiation damage to normal tissues is one of the most serious concerns in radiation therapy, and the tolerance dose of the normal tissues limits the therapeutic dose to the patients. p53 is well known as a transcription factor closely associated with radiation-induced cell death. We recently demonstrated the protective effects of several p53 regulatory agents against low-LET X- or γ-ray-induced damage. Although it was reported that high-LET heavy ion radiation (>85 keV/μm) could cause p53-independent cell death in some cancer cell lines, whether there is any radioprotective effect of the p53 regulatory agents against the high-LET radiation injury in vivo is still unclear. In the present study, we verified the efficacy of these agents on bone marrow and intestinal damages induced by high-LET heavy-ion irradiation in mice. We used a carbon-beam (14 keV/μm) that was shown to induce a p53-dependent effect and an iron-beam (189 keV/μm) that was shown to induce a p53-independent effect in a previous study. Vanadate significantly improved 60-day survival rate in mice treated with total-body carbon-ion (p < 0.0001) or iron-ion (p < 0.05) irradiation, indicating its effective protection of the hematopoietic system from radiation injury after high-LET irradiation over 85 keV/μm. 5CHQ also significantly increased the survival rate after abdominal carbon-ion (p < 0.02), but not iron-ion irradiation, suggesting the moderate relief of the intestinal damage. These results demonstrated the effectiveness of p53 regulators on acute radiation syndrome induced by high-LET radiation

テニス キョウギ ニオケル スピード ジキュウセイ ヒョウカ ノタメノ フィールド テスト ニカンスル イチコウサツ

In recent years tennis rallies have increased in speed. Furthermore, several recent cases have been described in which mean blood lactate levels approached the onset of blood lactate accumulation (OBLA). Defining contemporary tennis as an intermittent higIn recent years tennis rallies have increased in speed Furthermore, several recent cases\u272】131 have beendescribed in which mean blood lactate levels approached the onset of blood lactate accumulation (OBLA).Defining contemporary tennis as an intermittent high intensity exercise, the authors aimed to determine a methodof evaluating the physical ability of speed endurance that tennis athletes are required to acquire at present. Thepurpose of this study was firstly to elucidate the optimum form of intermittent exercise for use as field test fortennis players, and secondly to clarify the relationships among speed endurance, ventilatory threshold (VT : %VChmax) and post-exercise blood lactate level.All subjects were tennis athletes (42 males and 34 females, ranging in age from 12 to 21 years) who competedat the university, regional (state), or national junior level. The physical tests evaluated were as follows :intermittent 5 m, 10 m and 40 m sprint runs, and intermittent 10 m shuttle runs, 10 m repeated double shuttle runsand intermittent 50 m change-of-direction runs. These exercises were performed as intermittent exercises andwere performed 10 times with 20-second intervals. Twelve-minute-runs, shuttle-stamina-test (10叩shuttle runsin 3 minutes), 10 sessions of intermittent pedaling (0.075% weight kp/5 second) with 20-second intervals, andtreadmill measurement of VT were also performed. Posトexercise blood lactate was sampled after the intermittentshuttle runs and the intermittent pedaling. Each series, composing 10 trials of the above-mentioned intermittentexercises, was divided into 4 phases : first phase (Isl trial), primal phase (2 to 4山trial), middle phase (5 to 7山trial), and final phase (81 to \u27th trial). The extent to which performance time in the final phase was prolonged incomparison to the previous phases was regarded an indicator of speed endurance

Inhibition of Chlorogenic Acid-induced Cytotoxicity by CoCl_2

Chlorogenic acid (CGA) induced apoptotic cell death in human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines. CGA exhibited oxidation Potential in the culture medium, as demonstrated by NO monitor. Both cytotoxic activity and oxidatoin potential were significantly reduced by addition of CoCl_2. ESR spectrascopy showed that CGA produced seven peaks of radicals under alkaline condition, while addition of CoCL_2 altered the spectral pattern and diminished the radical intensity of CCA. CoCl_2 accelerated the CGA-induced coloration of the culture medium and modified the difference spectrum at around 325 nm, an absorption maximum characteristic of CGA. These data suggest that CoCl_2 induced conformational changes in the CGA molecule. Chlorogenic acid (CGA) has shown diverse biological activities, including anti-HIV activity (1), antioxidant activity (2-4), anticarcinogenic activity (5-8), modulating activity of cytochrome P450-linked enzyme (9, 10) and antiallergic activity (11). We have recently reported that CGA induced cytotoxicity against human oral tumor cells (human oral squamous cell carcinoma HSC-2, human salivary gland tumor HSG) (12). The cytotoxic activity of CGA was significantly reduced by various antioxidants (catalase, sodium ascorbate, N-acetyl-L-cysteine) (13), suggesting that CGA induced cytotoxicity by its pro-oxidant action. However, the mechanism of cytotoxicity induction by CGA has not yet been elucidated. We have recently found that the cytotoxic activity of CGA was significantly reduced by COCI_2 (12). At present, there are at least two possibilities: one is that COCI_2 may directly interact with CGA and transform it into an inactive form, while a second one is that COCI_2 may induce transcription factors (4) which stimulate the gene expression of glycolytic enzymes and various growth factors necessary for cell survival. This study was undertaken to test the first possibility

Interaction between Chlorogenic Acid and Antioxidants

The interaction between chlorogenic acid (CGA) and antioxidants was investigated by two different parameters: radical intensity and cytotoxicity induction. ESR spectroscopy shows that CGA produced radicals under alkaline condition. The CGA radical was scavenged by 100-300-fold lower concentrations of sodium ascorbate or N-acetyl-l-cysteine (NAC), whereas the ascorbate radical was not completely scavenged by CGA. The cytotoxic activity of CGA ageinst human oral tumor cells (HSC-2, HSG) wa completely eliminated by lower concentrations of sodium ascorbate or NAC, whereas that of sodium ascorbate or NAC was only slightly reduced by CGA. The present study demonstrated that CGA ubdyces cytotoxicity by its radical-mediated oxidation mechanism and suggests the applicability ESR spectroscopy for the screening of drug to drug interaction