TGF-β promotes cell migration and invasion, an attribute that is linked to the pro-metastasis function of this cytokine in late stage cancers. The LIM 1863 colon carcinoma organoid undergoes ...epithelial-mesenchymal transition (EMT) in response to TGF-β. This process is markedly accelerated by TNF-α, and we found that the levels of miR-21 and miR-31 were prominently elevated under the synergistic actions of TGF-β/TNF-α. Consistent with this, overexpression of either miR-21 or miR-31 significantly enhanced the effect of TGF-β alone on LIM 1863 morphological changes. More importantly, transwell assays demonstrated the positive effects of both miR-21 and miR-31 in TGF-β regulation of LIM 1863 motility and invasiveness. Elevated levels of miR-21 and miR-31 also enhanced motility and invasiveness of other colon carcinoma cell lines. We present compelling evidence that TIAM1, a guanidine exchange factor of the Rac GTPase, is a direct target of both miR-21 and miR-31. Indeed in LIM 1863 cells, suppression of TIAM1 is required for miR-21/miR-31 to enhance cell migration and invasion. Therefore, we have uncovered miR-21 and miR-31 as downstream effectors of TGF-β in facilitating invasion and metastasis of colon carcinoma cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cellulose is the most abundant biomass on Earth, and many microorganisms depend on it as a source of energy. It consists mainly of crystalline and amorphous regions, and natural degradation of the ...crystalline part is highly dependent on the degree of processivity of the degrading enzymes (i.e., the extent of continuous hydrolysis without detachment from the substrate cellulose). Here, we report high-speed atomic force microscopic (HS-AFM) observations of the movement of four types of cellulases derived from the cellulolytic bacteria Cellulomonas fimi on various insoluble cellulose substrates. The HS-AFM images clearly demonstrated that two of them (CfCel6B and CfCel48A) slide on crystalline cellulose. The direction of processive movement of CfCel6B is from the nonreducing to the reducing end of the substrate, which is opposite that of processive cellulase Cel7A of the fungus Trichoderma reesei (TrCel7A), whose movement was first observed by this technique, while CfCel48A moves in the same direction as TrCel7A. When CfCel6B and TrCel7A were mixed on the same substrate, “traffic accidents” were observed, in which the two cellulases blocked each other’s progress. The processivity of CfCel6B was similar to those of fungal family 7 cellulases but considerably higher than those of fungal family 6 cellulases. The results indicate that bacteria utilize family 6 cellulases as high-processivity enzymes for efficient degradation of crystalline cellulose, whereas family 7 enzymes have the same function in fungi. This is consistent with the idea of convergent evolution of processive cellulases in fungi and bacteria to achieve similar functionality using different protein foldings.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Identifying and understanding reasons for being unsure or unwilling regarding intention to be vaccinated against coronavirus disease (COVID-19) may help to inform future public health messages aimed ...at increasing vaccination coverage. We analyzed a broad array of individual's psychological dispositions with regard to decision-making about COVID-19 vaccination in Japan.
A nationally representative cross-sectional web survey was conducted with 30053 Japanese adults aged 20 years or older at the end of February 2021. In addition to the question on the individual's intention to be vaccinated against COVID-19, respondents were asked about their sociodemographic, health-related, and psychological characteristics as well as information sources about COVID-19 and their levels of trust. Also, those who responded ‘not sure’ or ‘no’ regarding intention to take COVID-19 vaccine were asked why. Multinomial logistic regression with sparse group Lasso (Least Absolute Shrinkage and Selection Operator) penalty was used to compute adjusted odds ratios for factors associated with the intention (not sure/no versus yes).
The percentages of respondents who answered ‘not sure’ or ‘no’ regarding intention to be vaccinated against COVID-19 vaccine were 32.9% and 11.0%, respectively. After adjusting for covariates, the perceived risks of COVID-19, perceived risk of a COVID-19 vaccine, perceived benefits of a COVID-19 vaccine, trust in scientists and public authorities, and the belief that healthcare workers should be vaccinated were significantly associated with vaccination intention. Several sources of information about COVID-19 were also significantly associated with vaccination intention, including physicians, nurses, and television, medical information sites with lower odds of being unsure or unwilling, and internet news sites, YouTube, family members, and scientists and researchers with higher odds. The higher the level of trust in television as a source of COVID-19 information, the higher the odds of responding ‘not sure’ (odds ratio 1.11, 95% confidence interval 1.01–1.21). We also demonstrated that many respondents presented concerns about the side effects and safety of a COVID-19 vaccine as a major reason for being unsure or unwilling. To decide whether or not to get the vaccine, many respondents requested more information about the compatibilities between the vaccine and their personal health conditions, whether other people had been vaccinated, the effectiveness of vaccines against variants, and doctors’ recommendations.
Our findings suggest that public health messaging based on the sociodemographic and psychological characteristics of those who are unsure or unwilling regarding intention to be vaccinated against COVID-19 vaccine may help to increase vaccine uptake amongst this population.
The present work was supported in part by a grant from the Ministry of Health, Labour and Welfare of Japan (H29-Gantaisaku-ippan-009).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Arabinogalactan proteins (AGPs) are a complex family of cell‐wall proteoglycans that are thought to play major roles in plant growth and development. Genetic approaches to studying AGP ...function have met limited success so far, presumably due to redundancy within the large gene families encoding AGP backbones. Here we used an alternative approach for genetic dissection of the role of AGPs in development by modifying their glycan side chains. We have identified an Arabidopsis glycosyltransferase of CAZY family GT31 (AtGALT31A) that galactosylates AGP side chains. A mutation in the AtGALT31A gene caused the arrest of embryo development at the globular stage. The presence of the transcript in the suspensor of globular‐stage embryos is consistent with a role for AtGALT31A in progression of embryo development beyond the globular stage. The first observable defect in the mutant is perturbation of the formative asymmetric division of the hypophysis, indicating an essential role for AGP proteoglycans in either specification of the hypophysis or orientation of the asymmetric division plane.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
The electrical properties of DNA have been extensively investigated within the field of molecular electronics. Previous studies on this topic primarily focused on the transport phenomena in ...the static structure at thermodynamic equilibria. Consequently, the properties of higher-order structures of DNA and their structural changes associated with the design of single-molecule electronic devices have not been fully studied so far. This stems from the limitation that only extremely short DNA is available for electrical measurements, since the single-molecule conductance decreases sharply with the increase in the molecular length. Here, we report a DNA zipper configuration to form a single-molecule junction. The duplex is accommodated in a nanogap between metal electrodes in a configuration where the duplex is perpendicular to the nanogap axis. Electrical measurements reveal that the single-molecule junction of the 90-mer DNA zipper exhibits high conductance due to the delocalized π system. Moreover, we find an attractive self-restoring capability that the single-molecule junction can be repeatedly formed without full structural breakdown even after electrical failure. The DNA zipping strategy presented here provides a basis for novel designs of single-molecule junctions.
Abstract
BRCA1 plays an important roles in several biological events during the DNA damage response (DDR). Recently, some reports have indicated that BRCA1 dysfunction is involved in the pathogenesis ...of Alzheimer disease (AD). Furthermore, it has also been reported that BRCA1 accumulates within neurofibrillary tangles (NFTs) in the AD brain. In this study, we examined the immunohistochemical distribution of BRCA1 and another DDR protein, p53-Binding Protein 1 (53BP1), in AD, Pick disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration, and frontotemporal dementia with parkinsonism linked to chromosome 17. In control subjects, neither BRCA1 nor phosphorylated BRCA1 (pBRCA1; Ser1524) immunoreactivity was observed in neurons or glial cells; and that for pBRCA1 (Ser1423) and 53BP1 were slightly detected in neuronal nuclei. The immunoreactivity for both BRCA1 and pBRCA1 (Ser1423) was localized within phosphorylated tau inclusions in all tauopathies, whereas that for pBRCA1 (Ser1524) was mainly associated with Pick bodies in PiD and to a lesser extent with NFTs in AD. On the other hand, 53BP1-immunoreactive deposits tended to be increased in the nucleus of neurons in AD and PSP compared with those in control cases. Our results suggest that DDR dysfunction due to cytoplasmic sequestration of BRCA1 could be involved in the pathogenesis of tauopathies.
Substrate specificities of glycoside hydrolase families 8 (Rex), 39 (
Bh
Xyl39), and 52 (
Bh
Xyl52) β-xylosidases from
Bacillus halodurans
C-125 were investigated.
Bh
Xyl39 hydrolyzed xylotriose most ...efficiently among the linear xylooligosaccharides. The activity decreased in the order of xylohexaose > xylopentaose > xylotetraose and it had little effect on xylobiose. In contrast,
Bh
Xyl52 hydrolyzed xylobiose and xylotriose most efficiently, and its activity decreased when the main chain became longer as follows: xylotetraose > xylopentaose > xylohexaose. Rex produced
O
-β-D-xylopyranosyl-(1 → 4)-
O
-α-L-arabinofuranosyl-(1 → 3)-
O
-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranose (Ara
2
Xyl
3
) and
O
-β-D-xylopyranosyl-(1 → 4)-
O
-4-
O
-methyl-α-D-glucuronopyranosyl-(l → 2)-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranose (MeGlcA
2
Xyl
3
), which lost a xylose residue from the reducing end of
O
-β-D-xylopyranosyl-(1 → 4)-
O
-α-L-arabinofuranosyl-(1 → 3)-
O
-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranose (Ara
3
Xyl
4
) and
O
-β-D-xylopyranosyl-(1 → 4)-
O
-4-
O
-methyl-α-D-glucuronopyranosyl-(1 → 2)-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranose (MeGlcA
3
Xyl
4
). It was considered that there is no space to accommodate side chains at subsite −1.
Bh
Xyl39 rapidly hydrolyzes the non-reducing-end xylose linkages of MeGlcA
3
Xyl
4
, while the arabinose branch does not significantly affect the enzyme activity because it degrades Ara
3
Xyl
4
as rapidly as unmodified xylotetraose. The model structure suggested that
Bh
Xyl39 enhanced the activity for MeGlcA
3
Xyl
4
by forming a hydrogen bond between glucuronic acid and Lys265.
Bh
Xyl52 did not hydrolyze Ara
3
Xyl
4
and MeGlcA
3
Xyl
4
because it has a narrow substrate binding pocket and 2- and 3-hydroxyl groups of xylose at subsite +1 hydrogen bond to the enzyme.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Specifying the geometric and electronic structures of a metal–molecule interface at the single-molecule level is crucial for the improvement of organic electronics. A single-molecule junction (SMJ) ...can be used to investigate interfaces because it can be regarded as an elementary unit of the interface structure. Although considerable efforts have been made to this end, the detection of structural changes in SMJs associated with metal–molecule interactions remains challenging. In this study, we detected the surface-enhanced Raman scattering (SERS) signal originating from the metal–molecule interaction change induced by a local structural change in a C60 SMJ. This junction has attracted wide attention owing to its unique electronic and vibronic properties. We fabricated a C60 SMJ using a lithographically fabricated Au electrode and measured the SERS spectra along with the current–voltage (I–V) response. By continuous measurement of SERS for the C60 SMJ, we obtained SERS spectra dependent on the local structural change. The analysis of the I–V response revealed that the vibration energy shift originates from the change in the local structure for different Au–C60 interactions. Based on the discrimination of the states in accordance with the Au–C60 interaction, we found that the probability of SERS for geometry with a large Au–C60 interaction was enhanced.
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IJS, KILJ, NUK, PNG, UL, UM
Hydrothermal reaction is known to be one of the most efficient procedures to extract hemicelluloses from lignocellulosic biomass. We investigated the molecular structure of xylooligosaccharides ...released from corn cob in a continuous flow type hydrothermal reactor designed in our group. The fraction precipitable from the extract with four volumes of ethanol was examined by 1H-NMR spectroscopy and MALDI-TOF MS before and after enzymatic treatment with different purified enzymes. The released water-soluble hemicellulose was found to correspond to a mixture of wide degree of polymerization range of acetylarabinoglucuronoxylan fragments (further as corn cob xylan abbreviated CX). Analysis of enzymatic hydrolyzates of CX with an acetylxylan esterase, GH3 β-xylosidase, GH10 and GH11 xylanases revealed that the main chain contains unsubstituted regions mixed with regions of xylopyranosyl residues partially acetylated and occasionally substituted by 4-O-methyl-d-glucuronic acid and arabinofuranose esterified with ferulic or coumaric acid. Single 2- and 3-O-acetylation was accompanied by 2,3-di-O-acetylation and 3-O-acetylation of Xylp residues substituted with MeGlcA. Most of the non-esterified arabinofuranose side residues were lost during the hydrodynamic process. Despite reduced branching, the acetylation and ferulic acid modification of pentose residues contribute to high yields and high solubility of the extracted CX. It is also shown that different enzyme treatments of CX may lead to various types of xylooligosaccharides of different biomedical potential.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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