63 research outputs found

    Chfr is linked to tumour metastasis through the downregulation of HDAC1

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    Chfr is a ubiquitin ligase that functions in the mitotic checkpoint by delaying entry into metaphase in response to mitotic stress. It has been suggested that Chfr is a tumour suppressor as Chfr is frequently silenced in human cancers. To better understand how Chfr activity relates to cell-cycle progression and tumorigenesis, we sought to identify Chfr-interacting proteins using affinity purification combined with mass spectrometry. Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Ectopic expression of Chfr in cancer cells that normally do not express it results in downregulation of HDAC1, leading to upregulation of the Cdk inhibitor p21^(CIP1/WAF1) and the metastasis suppressors KAI1 and E-cadherin. Coincident with these changes, cells arrest in the G1 phase of the cell cycle and become less invasive. Collectively, our data suggest that Chfr functions as a tumour suppressor by regulating HDAC1

    Amyloid Precursor Protein Binding Protein-1 Modulates Cell Cycle Progression in Fetal Neural Stem Cells

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    Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of the amyloid precursor protein (APP) and serves as the bipartite activation enzyme for the ubiquitin-like protein, NEDD8. In the present study, we explored the physiological role of APP-BP1 in the cell cycle progression of fetal neural stem cells. Our results show that cell cycle progression of the cells is arrested at the G1 phase by depletion of APP-BP1, which results in a marked decrease in the proliferation of the cells. This action of APP-BP1 is antagonistically regulated by the interaction with APP. Consistent with the evidence that APP-BP1 function is critical for cell cycle progression, the amount of APP-BP1 varies depending upon cell cycle phase, with culminating expression at S-phase. Furthermore, our FRET experiment revealed that phosphorylation of APP at threonine 668, known to occur during the G2/M phase, is required for the interaction between APP and APP-BP1. We also found a moderate ubiquitous level of APP-BP1 mRNA in developing embryonic and early postnatal brains; however, APP-BP1 expression is reduced by P12, and only low levels of APP-BP1 were found in the adult brain. In the cerebral cortex of E16 rats, substantial expression of both APP-BP1 and APP mRNAs was observed in the ventricular zone. Collectively, these results indicate that APP-BP1 plays an important role in the cell cycle progression of fetal neural stem cells, through the interaction with APP, which is fostered by phopshorylation of threonine 668

    Elective Laparoscopic Repair after Colonoscopic Decompression for Incarcerated Morgagni Hernia

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    Plain radiographs of an 88-year-old woman who had experienced vomiting and abdominal distention for 3 days revealed a severely obstructed ileus, and abdominopelvic computed tomography revealed an incarcerated Morgagni hernia. The endoscope was passed through the constrictions from the diaphragmatic indentations and a thin catheter was placed for decompression. The obstructive ileus regressed markedly after the procedure; the patient underwent elective laparoscopic repair of the hernia 1 week later. This is believed to be the first case of endoscopic preoperative decompression for an incarcerated Morgagni hernia

    Genotypic Heterogeneity of Orientia tsutsugamushi in Scrub Typhus Patients and Thrombocytopenia Syndrome Co-infection, Myanmar

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    Serologic and molecular surveillance of serum collected from 152 suspected scrub typhus patients in Myanmar revealed Orientia tsutsugamushi of genotypic heterogeneity. In addition, potential co-infection with severe fever with thrombocytopenia syndrome virus was observed in 5 (3.3%) patients. Both scrub typhus and severe fever with thrombocytopenia syndrome are endemic in Myanmar.Y

    SNP assay to detect the ‘Hyuuga’ red-brown lesion resistance gene for Asian soybean rust

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    Asian soybean rust (ASR), caused by Phakopsora pachyrhizi Syd., has the potential to become a serious threat to soybean, Glycine max L. Merr., production in the USA. A novel rust resistance gene, Rpp?(Hyuuga), from the Japanese soybean cultivar Hyuuga has been identified and mapped to soybean chromosome 6 (Gm06). Our objectives were to fine-map the Rpp?(Hyuuga) gene and develop a high-throughput single nucleotide polymorphism (SNP) assay to detect this ASR resistance gene. The integration of recombination events from two different soybean populations and the ASR reaction data indicates that the Rpp?(Hyuuga) locus is located in a region of approximately 371 kb between STS70887 and STS70923 on chromosome Gm06. A set of 32 ancestral genotypes which is predicted to contain 95% of the alleles present in current elite North American breeding populations and the sources of the previously reported ASR resistance genes (Rpp1, Rpp2, Rpp3, Rpp4, Rpp5, and rpp5) were genotyped with five SNP markers. We developed a SimpleProbe assay based on melting curve analysis for SNP06-44058 which is tighly linked to the Rpp?(Hyuuga) gene. This SNP assay can differentiate plants/lines that are homozygous/homogeneous or heterozygous/heterogeneous for the resistant and susceptible alleles at the Rpp?(Hyuuga) locus

    Vertical distributions of organic matter components in sea ice near Cambridge Bay, Dease Strait, Canadian Archipelago

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    Ice algae thriving within sea ice play a crucial role in transferring energy to higher trophic levels and influencing biogeochemical processes in polar oceans; however, the distribution of organic matter within the ice interior is not well understood. This study aimed to investigate the vertical distribution of organic matter, including chlorophyll a (Chl-a), particulate organic carbon and nitrogen (POC and PON), carbohydrates (CHO), proteins (PRT), lipids (LIP), and food material (FM), within the sea ice. Samples were collected from the bottom, middle, and top sections of the sea ice column near Cambridge Bay during the spring of 2018. Based on the δ13C signature, biochemical composition, and POC contribution of biopolymeric carbon (BPC), the organic substances within the sea ice were predominantly attributed to marine autotrophs. While the highest concentrations of each parameter were observed at the sea ice bottom, notable concentrations were also found in the upper sections. The average sea ice column-integrated Chl-a concentration was 5.05 ± 2.26 mg m−2, with the bottom ice section contributing 59% (S.D. = ± 10%) to the total integration. The column-integrated concentrations of FM, BPC, POC, and PON were 2.05 ± 0.39, 1.10 ± 0.20, 1.47 ± 0.25, and 0.09 ± 0.03 g m−2, respectively. Contributions of the bottom ice section to these column-integrated concentrations varied for each parameter, with values of 20 ± 6, 21 ± 7, 19 ± 5, and 28 ± 7%, respectively. While the bottom ice section exhibited a substantial Chl-a contribution in line with previous studies, significantly higher contributions of the other parameters were observed in the upper sea ice sections. This suggests that the particulate matter within the interior of the sea ice could potentially serve as an additional food source for higher trophic grazers or act as a seeding material for a phytoplankton bloom during the ice melting season. Our findings highlight the importance of comprehensive field measurements encompassing the entire sea ice section to better understand the distribution of organic carbon pools within the sea ice in the Arctic Ocean

    Prevalence of Neuropathic Pain and Patient-Reported Outcomes in Korean Adults with Chronic Low Back Pain Resulting from Neuropathic Low Back Pain

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    Study DesignA noninterventional, multicenter, cross-sectional study.PurposeWe investigated the prevalence of neuropathic pain (NP) and patient-reported outcomes (PROs) of the quality of life (QoL) and functional disability in Korean adults with chronic low back pain (CLBP).Overview of LiteratureAmong patients with CLBP, 20%–55% had NP.MethodsPatients older than 20 years with CLBP lasting for longer than three months, with a visual analog scale (VAS) pain score higher than four, and with pain medications being used for at least four weeks before enrollment were recruited from 27 general hospitals between December 2014 and May 2015. Medical chart reviews were performed to collect demographic/clinical features and diagnosis of NP (douleur neuropathique 4, DN4). The QoL (EuroQoL 5-dimension, EQ-5D; EQ-VAS) and functional disability (Quebec Back Pain Disability Scale, QBPDS) were determined through patient surveys. Multiple linear regression analyses were performed to compare PROs between the NP (DN4≥4) and non-NP (DN4<4) groups.ResultsA total of 1,200 patients (females: 65.7%; mean age: 63.4±13.0 years) were enrolled. The mean scores of EQ-5D, EQ-VAS, and QBPDS were 0.5±0.3, 55.7±19.4, and 40.4±21.1, respectively. Among all patients, 492 (41.0%; 95% confidence interval, 38.2%–43.8%) suffered from NP. The prevalence of NP was higher in male patients (46.8%; p<0.01), in patients who had pain based on radiological and neurological findings (59.0%; p<0.01), and in patients who had severe pain (49.0%; p<0.01). There were significant mean differences in EQ-5D (NP group vs. non-NP group: 0.4±0.3 vs. 0.5±0.3; p<0.01) and QBPDS (NP group vs. non-NP group: 45.8±21.2 vs. 36.3±20.2; p<0.01) scores. In the multiple linear regression, patients with NP showed lower EQ-5D (β=−0.1; p<0.01) and higher QBPDS (β=7.0; p<0.01) scores than those without NP.ConclusionsNP was highly prevalent in Korean patients with CLBP. Patients with CLBP having NP had a lower QoL and more severe dysfunction than those without NP. To enhance the QoL and functional status of patients with CLBP, this study highlights the importance of appropriately diagnosing and treating NP

    World Congress Integrative Medicine & Health 2017: Part one

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    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    High-Throughput Phenotypic Characterization and Diversity Analysis of Soybean Roots (<i>Glycine max</i> L.)

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    Soybean (Glycine max L.) is a crop native to Northeast Asia, including China, Korea, and Japan, but currently cultivated all over the world. The National Agrobiodiversity Center in Korea at the Rural Development Administration (RDA) conserves approximately 26,000 accessions and conducts characterizations of its accessions, to accumulate new information. Roots are essential organs of a plant, providing mechanical support, as well as aiding water and nutrient acquisition. Currently, not much information is available in international gene banks regarding root characterization. We studied the root phenotype of 374 soybean accessions, using a high-throughput method. Eight root morphological traits (RMT) were studied and we observed that the surface area (SA), number of forks (NF), and number of tips (NT) had a positive correlation with total length (LENGTH), and that link average length (LAL) and other traits all had a negative correlation. Additionally, the correlation between seed traits (height, width, and 100-seed weight) and root traits was confirmed for the first time in this experiment. The germplasms were divided into three clusters by k-means clustering, and orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to compare clusters. The most distinctive characteristics between clusters were total lateral average length (LAD) and total lateral average length (DIAM). Cluster 3 had the highest LENGTH, SA, NF, and NF, whereas cluster 1 had the smallest LENGTH, SA, and NF. We selected the top 10 accessions for each RMT, and IT208321, IT216313, and IT216137 were nominated as the best germplasms. These accessions can be recommended to breeders as materials for breeding programs. This is a preliminary report on the characterization of the root phenotype at an international gene bank and will open up the possibility of improving the available information on accessions in gene banks worldwide
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