Pinpoint-fluorinated polycyclic aromatic hydrocarbons (F-PAHs): Syntheses of difluorinated subfamily and their properties

Difluorinated polycyclic aromatic hydrocarbons (PAHs) containing three to five benzene rings were systematically synthesized by the Pd(II)-catalyzed Friedel–Crafts-type cyclization of 1,1,2-trifluoro- and 1,1-difluoro-1-alkenes and the In(III)-catalyzed tandem cyclization of bis(1,1-difluoroallene)s. Using an array of the difluorinated PAHs that were obtained and previously reported monofluorinated PAHs, the physical properties of the pinpoint-fluorinated PAHs were investigated. (i) The 19F NMR signals of the bay-region fluorine atoms were shifted downfield by ca. 8–14 ppm for vic-difluorinated PAHs and ca. 11–19 ppm for non-vic-difluorinated and monofluorinated PAHs. (ii) The introduction of fluorine into PAH molecules increased their solubilities in organic solvents, which was best exemplified by the high solubilities of 6,7-difluoropicene (5.4 wt%) and 6-fluoropicene (5.3 wt%) in THF. (iii) The HOMO–LUMO energy gaps of the pinpoint-fluorinated PAHs were smaller than that of the corresponding fluorine-free PAH (i.e., picene) by 0.02–0.26 eV, and the HOMO and LUMO energy levels were lowered by 0.10–0.22 eV and 0.12–0.41 eV, respectively

TUFT1 interacts with RABGAP1 and regulates mTORC1 signaling

The mammalian target of rapamycin (mTOR) pathway is commonly activated in human cancers. The activity of mTOR complex 1 (mTORC1) signaling is supported by the intracellular positioning of cellular compartments and vesicle trafficking, regulated by Rab GTPases. Here we showed that tuftelin 1 (TUFT1) was involved in the activation of mTORC1 through modulating the Rab GTPase-regulated process. TUFT1 promoted tumor growth and metastasis. Consistently, the expression of TUFT1 correlated with poor prognosis in lung, breast and gastric cancers. Mechanistically, TUFT1 physically interacted with RABGAP1, thereby modulating intracellular lysosomal positioning and vesicular trafficking, and promoted mTORC1 signaling. In addition, expression of TUFT1 predicted sensitivity to perifosine, an alkylphospholipid that alters the composition of lipid rafts. Perifosine treatment altered the positioning and trafficking of cellular compartments to inhibit mTORC1. Our observations indicate that TUFT1 is a key regulator of the mTORC1 pathway and suggest that it is a promising therapeutic target or a biomarker for tumor progression.UTokyo FOCUS Articles掲載「がんの増殖・転移を促進する新規因子の同定 小胞輸送を標的とする新しいがん治療戦略への可能性」 https://www.u-tokyo.ac.jp/focus/ja/articles/z0508_00119.htmlUTokyo FOCUS Articles "Possible target for future cancer treatment : Deregulation of system to move molecules in the cell may promote tumor growth, metastasis" https://www.u-tokyo.ac.jp/focus/en/articles/z0508_00120.htm

Tumor-promoting functions of transforming growth factor-β in progression of cancer

Transforming growth factor-β (TGF-β) elicits both tumor-suppressive and tumor-promoting functions during cancer progression. Here, we describe the tumor-promoting functions of TGF-β and how these functions play a role in cancer progression. Normal epithelial cells undergo epithelial-mesenchymal transition (EMT) through the action of TGF-β, while treatment with TGF-β and fibroblast growth factor (FGF)-2 results in transdifferentiation into activated fibroblastic cells that are highly migratory, thereby facilitating cancer invasion and metastasis. TGF-β also induces EMT in tumor cells, which can be regulated by oncogenic and anti-oncogenic signals. In addition to EMT promotion, invasion and metastasis of cancer are facilitated by TGF-β through other mechanisms, such as regulation of cell survival, angiogenesis, and vascular integrity, and interaction with the tumor microenvironment. TGF-β also plays a critical role in regulating the cancer-initiating properties of certain types of cells, including glioma-initiating cells. These findings thus may be useful for establishing treatment strategies for advanced cancer by inhibiting TGF-β signaling

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

Efficacy of forming biofilms by naphthalene degrading Pseudomonas stutzeri T102 toward bioremediation technology and its molecular mechanisms

In natural environments, bacteria often exist in close association with surfaces and interfaces. There they form "biofilms", multicellular aggregates held together by an extracellular matrix. The biofilms confer on the constituent cells high resistance to environmental stresses and diverse microenvironments that help generate cellular heterogeneity. Here we report on the ability of Pseudomonas stutzeri T102 biofilm-associated cells, as compared with that of planktonic cells, to degrade naphthalene and survive in petroleum-contaminated soils. In liquid culture system. T102 biofilm-associated cells did not degrade naphthalene during initial hours of incubation but then degraded it faster than planktonic cells, which degraded naphthalene at a nearly constant rate. This delayed but high degradation activity of the biofilms could be attributed to super-activated cells that were detached from the biofilms. When the fitness of T102 biofilm-associated cells was tested in natural petroleum-contaminated soils, they were capable of surviving for 10 wk; by then T102 planktonic cells were mostly extinct. Naphthalene degradation activity in the soils that had been inoculated with T102 biofilms was indeed higher than that observed in soils inoculated with T102 planktonic cells. These results suggest that inoculation of contaminated soils with P. stutzeri T102 biofilms should enable bioaugmentation to be a more durable and effective bioremediation technology than inoculation with planktonic cells

Effect of laminated structure on mechanical properties of composition-modulated Co-Ni laminated plating

A composition-modulated Co–Ni laminated plating has been developed to prolong the lifetime of molds to be employed in continuous steel casting. We have investigated the relationship between the laminated structure and the mechanical properties of the plating films. The tensile strength of as-plated film was enhanced by the thinned thickness of the constituent layers, while the elongation received no effect of the thickness change of the constituent layer and remained almost stable in the range from 3 to 5%. Heat treatment at 400°C have brought about the improvement both in the tensile strength and the elongation. The improvement in the elongation was as remarkable as reached 13% in the film composed of layers with a thickness of 0.8 µm. The layer with low Ni content had an hcp structure, and that with high Ni content produced two phases of the hcp and fcc structures in the as-plated state. By the heat treatment, the high Ni-content layer turned into the single fcc phase, while the low Ni-content layer kept the hcp phase, and accordingly, the film structure changed into the one where the lamination of the hcp and fcc layers was distinct. The fact that the fcc layers, which was easily deformed, were formed continuously in the lateral direction, was seemed to contribute to the significant improvement in the elongation after heat treatment

Time-related change evaluation of the cerebrospinal fluid using postmortem CT

Purpose: We retrospectively evaluated the cerebro-spinal fluid (CSF) CT density at the lateral ventricle to compare the postmortem intervals in cadavers. Materials and methods: The number of cadavers enrolled in this study was 189 (male 120, female 69). According to the estimated postmortem time, the cadavers were divided into 13 groups (postmortem day 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 7, 10, 14, 21, 30), and were also re-grouped into 3 groups according to the postmortem time-width: group A (postmortem day 0.5-2.5), group B (day 3-7), and group C (day 10-30). Comparisons between the CSF density and estimated postmortem time were also analyzed. Results: The CSF density was around 20 HU up to day 2.5, and it increased gradually after day 3. Day 3 and 4 presented higher CSF density than day 1 and 1.5 (p < 0.05). Day 7 presented higher CSF density than day 3 (p < 0.05). According to the postmortem time-width, the CSF density increased with postmortem time (p < 0.05). The simple linear regression equations presented negative correlation between CSF density and estimated postmortem time, and R2 was 0.119. Conclusion: The CSF density increased, but not linearly, according to the postmortem time, and the 3rd postmortem day was the earliest time allowing the difference to be detected. The CSF density needs further evaluation to enable estimation of the postmortem time