209 research outputs found

    t(8;21)(q24;q22) in prostate cancer

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    Review on t(8;21)(q24;q22) in prostate cancer, with data on clinics, and the genes involved

    The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

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    The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

    Profitability and Nitrate Leaching Effects of Possible Farming Practice and System Changes Over South Dakota\u27s Big Sioux Aquifer: Case Farm No. 1 Summary

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    The overall goal of the SARE/Water Quality project was to determine whether economic incentives offered by recent environmental provisions of the Federal farm program are sufficient to induce Western Corn Belt/Northern Great Plains farmers in environmentally sensitive areas to adopt sustainable farming practices and systems. To attain this goal, four case farms were chosen to be involved in this study based on their size, soil types, cropping systems, topography, and management in the Big Sioux Aquifer study area

    Profitability and Nitrate Leaching Effects of Possible Farming Practice and System Changes Over South Dakota\u27s Big Sioux Aquifer: Case Farm No. 1 Summary

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    The overall goal of the SARE/Water Quality project was to determine whether economic incentives offered by recent environmental provisions of the Federal farm program are sufficient to induce Western Corn Belt/Northern Great Plains farmers in environmentally sensitive areas to adopt sustainable farming practices and systems. To attain this goal, four case farms were chosen to be involved in this study based on their size, soil types, cropping systems, topography, and management in the Big Sioux Aquifer study area

    Profitability and Nitrate Leaching Effects of Possible Farming Practice and System Changes Over South Dakota\u27s Big Sioux Aquifer: Case Farm No. 2 Summary

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    The overall goal of the SARE/Water Quality project was to determine whether economic incentives offered by recent environmental provisions of Federal farm program are sufficient to induce Western Corn Belt/Northern Plains farmers in environmentally sensitive areas to adopt sustainable fa practices and systems. To attain this goal, four case farms were chosen involved in this study based on their size, soil types, cropping systems, topography, and management in the Big Sioux Aquifer study area. Case Farm No. 2 is located in Moody County and followed a corn-soybean oats rotation on the acres focused on in the analysis prior to enrollment the Integrated Crop Management (ICM) program. It is a dry-land operation used conventional tillage prior to enrollment in the ICM program. The total operation consists of 1,858 acres, with 710 acres under the ICM program focused on 299 of those ICM acres in our analyses. Lamo and Clamo soils up the majority of the ICM crop acres. These are medium to fine-textured soils overlying a shallow drinking water aquifer

    Profitability and Nitrate Leaching Effects of Possible Farming Practice and System Changes Over South Dakota\u27s Big Sioux Aquifer: Case Farm No. 4 Summary

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    The overall goal of the SARE/Water Quality project was to determine whether economic incentives offered by recent environmental provisions of the Federal farm program are sufficient to induce Western Corn Belt/Northern Great Plains farmers in environmentally sensitive areas to adopt sustainable farming practices and systems. To attain this goal, four case farms were chosen to be involved in this study based on their size, soil types, cropping systems, topography, and management in the Big Sioux Aquifer study area. Case Farm No. 4 is located in Brookings County and followed a continuous corn rotation prior to enrollment in the Water Quality Incentive Program (WQIP). It is an irrigated operation that uses a center-pivot system. Conventional tillage practices are used. The total operation consists of 838 acres, with 213 acres enrolled in the WQIP program. One hundred and fifty of those acres received irrigation management assistance. In one 73-acre field irrigated by a center-pivot system, 66 acres were assumed to be under the center-pivot system and the other 7 acres were assumed to be in the corners of the field where the center-pivot system could not reach. These 7 acres were designated as the set-aside acres for the baseline before scenario. This 73-acre field was focused on in our analyses. The majority of the soils in this field are a combination of coarse-textured (Fordville), and fine-textured (Marysland) soils. Both of these soils overlay a shallow drinking water aquife

    A modular dCas9-SunTag DNMT3A epigenome editing system overcomes pervasive off-target activity of direct fusion dCas9-DNMT3A constructs

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    Detection of DNA methylation in the genome has been possible for decades; however, the ability to deliberately and specifically manipulate local DNA methylation states in the genome has been extremely limited. Consequently, this has impeded our understanding of the direct effect of DNA methylation on transcriptional regulation and transcription factor binding in the native chromatin context. Thus, highly specific targeted epigenome editing tools are needed to address this. Recent adaptations of genome editing technologies, including fusion of the DNMT3A DNA methyltransferase catalytic domain to catalytically inactive Cas9 (dC9-D3A), have aimed to alter DNA methylation at desired loci. Here, we show that these tools exhibit consistent off-target DNA methylation deposition in the genome, limiting their capabilities to unambiguously assess the functional consequences of DNA methylation. To address this, we developed a modular dCas9-SunTag (dC9Sun-D3A) system that can recruit multiple DNMT3A catalytic domains to a target site for editing DNA methylation. dC9Sun-D3A is tunable, specific, and exhibits much higher induction of DNA methylation at target sites than the dC9-D3A direct fusion protein. Importantly, genome-wide characterization of dC9Sun-D3A binding sites and DNA methylation revealed minimal off-target protein binding and induction of DNA methylation with dC9Sun-D3A, compared to pervasive off-target methylation by dC9-D3A. Furthermore, we used dC9Sun-D3A to demonstrate the binding sensitivity to DNA methylation for CTCF and NRF1 in situ. Overall, this modular dC9Sun-D3A system enables precise DNA methylation deposition with the lowest off-target DNA methylation levels reported to date, allowing accurate functional determination of the role of DNA methylation at single loci.Christian Pflueger, Dennis Tan, Tessa Swain, Trung Nguyen, Jahnvi Pflueger, Christian Nefzger ... et al

    Reduced P300 amplitude during retrieval on a spatial working memory task in a community sample of adolescents who report psychotic symptoms.

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    BACKGROUND: Deficits in working memory are widely reported in schizophrenia and are considered a trait marker for the disorder. Event-related potentials (ERPs) and imaging data suggest that these differences in working memory performance may be due to aberrant functioning in the prefrontal and parietal cortices. Research suggests that many of the same risk factors for schizophrenia are shared with individuals from the general population who report psychotic symptoms. METHODS: Forty-two participants (age range 11--13 years) were divided into those who reported psychotic symptoms (N = 17) and those who reported no psychotic symptoms, i.e. the control group (N = 25). Behavioural differences in accuracy and reaction time were explored between the groups as well as electrophysiological correlates of working memory using a Spatial Working Memory Task, which was a variant of the Sternberg paradigm. Specifically, differences in the P300 component were explored across load level (low load and high load), location (positive probe i.e. in the same location as shown in the study stimulus and negative probe i.e. in a different location to the study stimulus) and between groups for the overall P300 timeframe. The effect of load was also explored at early and late timeframes of the P300 component (250-430 ms and 430-750 ms respectively). RESULTS: No between-group differences in the behavioural data were observed. Reduced amplitude of the P300 component was observed in the psychotic symptoms group relative to the control group at posterior electrode sites. Amplitude of the P300 component was reduced at high load for the late P300 timeframe at electrode sites Pz and POz. CONCLUSIONS: These results identify neural correlates of neurocognitive dysfunction associated with population level psychotic symptoms and provide insights into ERP abnormalities associated with the extended psychosis phenotype
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