1,265 research outputs found

    Dispensability of Escherichia coli's latent pathways

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    Gene-knockout experiments on single-cell organisms have established that expression of a substantial fraction of genes is not needed for optimal growth. This problem acquired a new dimension with the recent discovery that environmental and genetic perturbations of the bacterium Escherichia coli are followed by the temporary activation of a large number of latent metabolic pathways, which suggests the hypothesis that temporarily activated reactions impact growth and hence facilitate adaptation in the presence of perturbations. Here we test this hypothesis computationally and find, surprisingly, that the availability of latent pathways consistently offers no growth advantage, and tends in fact to inhibit growth after genetic perturbations. This is shown to be true even for latent pathways with a known function in alternate conditions, thus extending the significance of this adverse effect beyond apparently nonessential genes. These findings raise the possibility that latent pathway activation is in fact derivative of another, potentially suboptimal, adaptive response

    POU2F1 activity regulates HOXD10 and HOXD11 promoting a proliferative and invasive phenotype in head and neck cancer

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    HOX genes are master regulators of organ morphogenesis and cell differentiation during embryonic development, and continue to be expressed throughout post-natal life. To test the hypothesis that HOX genes are dysregulated in head and neck squamous cell carcinoma (HNSCC) we defined their expression profile, and investigated the function, transcriptional regulation and clinical relevance of a subset of highly expressed HOXD genes. Two HOXD genes, D10 and D11, showed strikingly high levels in HNSCC cell lines, patient tumor samples and publicly available datasets. Knockdown of HOXD10 in HNSCC cells caused decreased proliferation and invasion, whereas knockdown of HOXD11 reduced only invasion. POU2F1 consensus sequences were identified in the 5’ DNA of HOXD10 and D11. Knockdown of POU2F1 significantly reduced expression of HOXD10 and D11 and inhibited HNSCC proliferation. Luciferase reporter constructs of the HOXD10 and D11 promoters confirmed that POU2F1 consensus binding sites are required for optimal promoter activity. Utilizing patient tumor samples a significant association was found between immunohistochemical staining of HOXD10 and both the overall and the disease-specific survival, adding further support that HOXD10 is dysregulated in head and neck cancer. Additional studies are now warranted to fully evaluate HOXD10 as a prognostic tool in head and neck cancers

    Pillar[6]arene acts as a biosensor for quantitative detection of a vitamin metabolite in crude biological samples

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    ビタミン代謝物を迅速定量できる超分子バイオセンサーを開発. 京都大学プレスリリース. 2020-12-09.Metabolic syndrome is associated with obesity, hypertension, and dyslipidemia, and increased cardiovascular risk. Therefore, quick and accurate measurements of specific metabolites are critical for diagnosis; however, detection methods are limited. Here we describe the synthesis of pillar[n]arenes to target 1-methylnicotinamide (1-MNA), which is one metabolite of vitamin B3 (nicotinamide) produced by the cancer-associated nicotinamide N-methyltransferase (NNMT). We found that water-soluble pillar[5]arene (P5A) forms host–guest complexes with both 1-MNA and nicotinamide, and water-soluble pillar[6]arene (P6A) selectively binds to 1-MNA at the micromolar level. P6A can be used as a “turn-off sensor” by photoinduced electron transfer (detection limit is 4.38 × 10−6 M). In our cell-free reaction, P6A is used to quantitatively monitor the activity of NNMT. Moreover, studies using NNMT-deficient mice reveal that P6A exclusively binds to 1-MNA in crude urinary samples. Our findings demonstrate that P6A can be used as a biosensor to quantify 1-MNA in crude biological samples

    Quantum critical spin-liquid-like behavior in S = 1/2 quasi-kagome lattice compound CeRh₁-ₓPdₓSn investigated using muon spin relaxation and neutron scattering

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    We present the results of muon spin relaxation (μSR) and neutron scattering on the Ce-based quasikagome lattice CeRh1−xPdxSn (x=0.1 to 0.75). Our ZF-μSR results reveal the absence of static long-range magnetic order down to 0.05~K in x=0.1 single crystals. The weak temperature-dependent plateaus of the dynamic spin fluctuations below 0.2~K in ZF-μSR together with its longitudinal-field (LF) dependence between 0 and 3~kG indicate the presence of dynamic spin fluctuations persisting even at T = 0.05~K without static magnetic order. On the other hand, C4f/T increases as --log T on cooling below 0.9~K, passes through a broad maximum at 0.13~K and slightly decreases on further cooling. The ac-susceptibility also exhibits a frequency independent broad peak at 0.16~K, which is prominent with an applied field H along c-direction. We, therefore, argue that such a behavior for x=0.1 (namely, a plateau in spin relaxation rate (λ) below 0.2~K and a linear T dependence in C4f below 0.13~K) can be attributed to a metallic spin-liquid (SL) ground state near the quantum critical point in the frustrated Kondo lattice. The LF-μSR study suggests that the out of kagome plane spin fluctuations are responsible for the SL behavior. Low energy inelastic neutron scattering (INS) of x = 0.1 reveals gapless magnetic excitations, which are also supported by the behavior of C4f proportional to T1.1 down to 0.06~K

    Referral from secondary care and to aftercare in a tertiary care university hospital in Japan

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    BACKGROUND: In Japan, all citizens are covered by the national insurance system in which universal free access to healthcare services is promised to everybody. There are no general physicians or gatekeepers in the Japanese healthcare system. METHODS: We studied the pattern of referral of inpatients from secondary care hospitals to a tertiary care university hospital and the reverse referral under the situations using a geographic information system (GIS), taking paediatric inpatients as an example. RESULTS: The results showed that 61.2% of the patients were directly admitted to the hospital without referral from other hospitals or clinics and that 82.8% of the inpatients were referred to the outpatient department of the hospital to which they had been admitted. GIS analysis for the inpatients service area showed the hospital functions as both a secondary care hospital and tertiary care hospital. Patients who lived near the hospital tended to be admitted directly to the hospital, and patients who lived far from the hospital tended to utilize the hospital as a tertiary care provider. There were territorial disputes with other secondary care hospitals. To estimate spatial differences in referral to aftercare, we analyzed the spatial distribution of inpatients with focus on their length of hospital stay (LOS). GIS analysis revealed apparent foci of patients with long LOS and those with low LOS. CONCLUSION: These results suggest that the function of university hospital in Japan is unspecialized and that the referral route from the university hospital to aftercare is also unequipped
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