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Co-delivery associated with doxorubicin as well as conferone simply by book pH-responsive β-cyclodextrin grafted micelles triggers apoptosis involving metastatic human breast cancer tissues.
In contrast, the additional Y chromosome in XYY males and XXY females diminishes the heterochromatic signal in these normally silenced, repeat-rich regions, which is accompanied by an increase in expression of Y-linked repeats. We find hundreds of genes that are expressed differentially between individuals with aberrant sex chromosome karyotypes, many of which also show sex-biased expression in wildtype Drosophila. Thus, Y-chromosomes influence heterochromatin integrity genome-wide, and differences in the chromatin landscape of males and females may also contribute to sex-biased gene expression and sexual dimorphisms. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.Despite its important biological role, the evolution of recombination rates remains relatively poorly characterized. This owes, in part, to the lack of high-quality genomic resources to address this question across diverse species. Humans and our closest evolutionary relatives, anthropoid apes, have remained a major focus of large-scale sequencing efforts, and thus recombination rate variation has been comparatively well-studied in this group - with earlier work revealing a conservation at the broad- but not the fine-scale. However, in order to better understand the nature of this variation, and the time-scales on which substantial modifications occur, it is necessary to take a broader phylogenetic perspective. I here present the first fine-scale genetic map for vervet monkeys based on whole genome population genetic data from ten individuals, and perform a series of comparative analyses with the great apes. The results reveal a number of striking features. Firstly, owing to strong positive correlations with diversity and weak negative correlations with divergence, analyses suggest a dominant role for purifying and background selection in shaping patterns of variation in this species. Secondly, results support a generally reduced broad-scale recombination rate compared to the great apes, as well as a narrower fraction of the genome in which the majority of recombination events are observed to occur. Taken together, this dataset highlights the great necessity of future research to identify genomic features and quantify evolutionary processes that are driving these rate changes across primates. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail [email protected] The aim of the study was to evaluate a technological solution in the form of an App to implement and measure person-centredness in nursing. The focus was to enhance the knowledge transfer of a set of person-centred key performance indicators and the corresponding measurement framework used to inform improvements in the experience of care. DESIGN The study used an evaluation approach derived from the work of the Medical Research Council to assess the feasibility of the App and establish the degree to which the App was meeting the aims set out in the development phase. Evaluation data were collected using focus groups (n = 7) and semi-structured interviews (n = 7) to capture the impact of processes experienced by participating sites. SETTING The study was conducted in the UK and Australia in two organizations, across 11 participating sites. PARTICIPANTS 22 nurses from 11 sites in two large health care organizations were recruited on a voluntary basis. INTERVENTION Implementing the KPIs and measurement framework via the APP through two cycles of data collection. MAIN OUTCOME MEASURES The main outcome was to establish feasibility in the use of the App. RESULTS The majority of nurse/midwife participants found the App easy to use. There was broad consensus that the App was an effective method to measure the patient experience and generated clear, concise reports in real time. CONCLUSIONS The implementation of the person-centred key performance indicators using the App enhanced the generation of meaningful data to evidence patient experience across a range of different clinical settings. © The Author(s) 2020. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail [email protected] study was performed to identify risk factors for pelvic nodal failure (PNF) after definitive concurrent chemo-radiotherapy (CCRT) in patients with metastatic pelvic lymph nodes (mPLNs) from squamous cell carcinoma (SCC) of the cervix. We retrospectively reviewed data on 80 patients who received definitive CCRT between 2005 and 2014 at our hospital. All patients underwent brachytherapy and whole-pelvic radiotherapy (WPRT) without nodal boost. mPLNs was diagnosed by magnetic resonance imaging and positron emission tomography. The rate of PNF and factors affecting PNF were analysed. A total of 156 mPLNs were found. The median number of mPLNs was 2 per patient (range 1-6); the median short diameter was 1.7 cm (range 1.0-4.2 cm). After a median follow-up of 64 months, 10 (6.4%) mPLNs failed in 13 (16.3%) patients. The 5-year PNF-free survival (PNFFS), disease-free survival and overall survival rates were 83.4, 62.7 and 74.7%, respectively. The mPLN size was not associated with the risk of PNF. However, pre-radiotherapy SCC antigen (SCC-Ag) >6.8 ng/mL and number of mPLNs >2 were significant risk factors for PNF. Using the two risk factors, we categorized the patients into three risk groups. The 5-year PNFFS rates in patients with 0, 1 and 2 risk factors were 100.0, 78.3 and 44.4%, respectively (P less then 0.01). SCC-Ag level and number of mPLNs were significant factors for PNF. Patients with both risk factors developed frequent PNF after WPRT without nodal boost. The two risk factors can be a guide in deciding whether to administer nodal boost radiotherapy. © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.Breast cancer (BC) is one of the most common malignancies globally in women, with high mortality rate as a result of tumor metastasis. MicroRNAs (miRNAs) play vital roles in the occurrence and development of human cancer. This study aimed to investigate the biological roles of miR-1323 in BC. The expression levels of miR-1323 were detected by quantitative real-time PCR assay. The effect of miR-1323 on BC cell proliferation was determined by MTT and colony formation assay. Wound healing analysis and Matrigel transwell assay were conducted to evaluate miR-1323-mediated BC cell migration and invasion. A luciferase reporter assay was used to test the target of miR-1323. We found that miR-1323 levels were downregulated in BC tissues and serums. Low-miR-1323 levels were associated with lymph node metastasis and advanced clinical stage. Tumor protein D52 (TPD52) was identified as a direct target of miR-1323. Low expression of miR-1323 contributed to the overexpression of TPD52 leading to enhanced BC progression. Our findings suggest that silencing of miR-1323 enhances BC development by regulating TPD52 expression, suggesting that miR-1323 and TPD52 may serve as potential therapeutic targets for BC treatment. © The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.Magnesium chelatase chlIDH and cobalt chelatase cobNST enzymes are required for biosynthesis of (bacterio)chlorophyll and cobalamin (vitamin B12), respectively. Each enzyme consists of large, medium and small subunits. Structural and primary sequence similarities indicate common evolutionary origin of the corresponding subunits. It has been reported earlier that some of vitamin B12 synthesizing organisms utilized unusual cobalt chelatase enzyme consisting of a large cobalt chelatase subunit (cobN) along with a medium (chlD) and a small (chlI) subunits of magnesium chelatase. In attempt to understand the nature of this phenomenon, we analyzed more than 1,200 diverse genomes of cobalamin and/or chlorophyll producing prokaryotes. We found that, surprisingly, genomes of many cobalamin producers contained cobN and chlD genes only; a small subunit gene was absent. Further on, we have discovered a diverse group of chlD genes with functional programmed ribosomal frameshifting (PRF) signals. Given a high similarity between the small subunit and the N-terminal part of the medium subunit, we proposed that programmed translational frameshifting may allow chlD mRNA to produce both subunits. Indeed, in genomes where genes for small subunits were absent, we observed statistically significant enrichment of programmed frameshifting signals in chlD genes. Interestingly, the details of the frameshifting mechanisms producing small and medium subunits from a single chlD gene could be prokaryotic taxa specific. All over, this programmed frameshifting phenomenon was observed to be highly conserved and present in both bacteria and archaea. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail [email protected] study characterized a new unshielded diode detector, the microSilicon (model 60023), for small-field photon beam dosimetry by evaluating the photon beams generated by a TrueBeam STx and a CyberKnife. Temperature dependence was evaluated by irradiating photons and increasing the water temperature from 11.5 to 31.3°C. For Diode E, microSilicon, microDiamond and EDGE detectors, dose linearity, dose rate dependence, energy dependence, percent-depth-dose (PDD), beam profiles and detector output factor (OFdet) were evaluated. The OFdet of the microSilicon detector was compared to the field output factors of the other detectors. BzATP triethylammonium datasheet The microSilicon exhibited small temperature dependence within 0.4%, although the Diode E showed a linear variation with a ratio of 0.26%/°C. The Diode E and EDGE detectors showed positive correlations between the detector reading and dose rate, whereas the microSilicon showed a stable response within 0.11%. The Diode E and microSilicon demonstrated negative correlations with the beam energy. The OFdet of microSilicon was the smallest among all the detectors. The maximum differences between the OFdet of microSilicon and the field output factors of microDiamond were 2.3 and 1.6% for 5 × 5 mm2 TrueBeam and 5 mm φ CyberKnife beams, respectively. The PDD data exhibited small variations in the dose fall-off region. The microSilicon and microDiamond detectors yielded similar penumbra widths, whereas the other detectors showed steeper penumbra profiles. The microSilicon demonstrated favorable characteristics including small temperature and dose rate dependence as well as the small spatial resolution and output factors suitable for small field dosimetry. © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.Aberrant DNA methylation is a common form of epigenetic alterations and it has been proved to be closely related to many cancers, while its role in EGFR-mutated non-small cell lung cancer (NSCLC) is not clear. This study focuses on the role of DNA methyltransferase 1 (DNMT1) in EGFR-mutated NSCLC pathogenesis. Firstly, the expression of DNMT1 was up-regulated while the expressions of human mutL homolog 1(hMLH1) and human mutS homolog2 (hMSH2) were down-regulated in EGFR-mutated NSCLC patients and cell line HCC827. The results of the correlation analysis showed that DNMT1 expression was inversely correlated to the expressions of hMLH1 and hMSH2. Then, we found that DNMT1 enhanced the promoter methylation levels of hMLH1 and hMSH2, thus suppressing their expressions. DNMT1 knockdown inhibited the proliferation of HCC827 cells, while both hMLH1 knockdown and hMSH2 knockdown could eliminate its inhibitory effect on cell proliferation. In xenograft mouse models, lentiviral vector-sh-DNMT1 could significantly reduce tumor volumes, confirmed that DNMT1 inhibited tumor cell proliferation in vivo.
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