17 research outputs found

    JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma

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    Chromosome 17q21-ter is commonly gained in neuroblastoma, but it is unclear which gene in the region is important for tumorigenesis. The JMJD6 gene at 17q21-ter activates gene transcription. Here we show that JMJD6 forms protein complexes with N-Myc and BRD4, and is important for E2F2, N-Myc and c-Myc transcription. Knocking down JMJD6 reduces neuroblastoma cell proliferation and survival in vitro and tumor progression in mice, and high levels of JMJD6 expression in human neuroblastoma tissues independently predict poor patient prognosis. In addition, JMJD6 gene is associated with transcriptional super-enhancers. Combination therapy with the CDK7/super-enhancer inhibitor THZ1 and the histone deacetylase inhibitor panobinostat synergistically reduces JMJD6, E2F2, N-Myc, c-Myc expression, induces apoptosis in vitro and leads to neuroblastoma tumor regression in mice, which are significantly reversed by forced JMJD6 over-expression. Our findings therefore identify JMJD6 as a neuroblastoma tumorigenesis factor, and the combination therapy as a treatment strategy

    Variation in δ13C values for different plant parts of an Oncidium orchid

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    Photosynthetica321135-139PHSY

    Microbial inoculation to improve plant performance in mine‐waste substrates: A test using pigeon pea (Cajanus cajan)

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    Mining activities alter soil physicochemical and biological properties that are critical for plant establishment. Revitalisation of soil biological properties via microbial inoculations can potentially be adopted to improve vegetation restoration. Here, we evaluate the feasibility of using beneficial microorganisms in the form of commercially available inoculants to enhance plant performance in a non-toxic and infertile mine-waste substrate, using pigeon pea [Cajanus cajan (L) Millsp.] as a test plant. Six treatments were established to investigate the effects of inoculants (Bradyrhizobium spp., microbial mix and uninoculated controls) and water availability (low and moderate) in a factorial design over 6 months. Plant performance was determined by physiological parameters (leaf gas exchange, leaf carbon, nitrogen and stable isotopes) and growth (height and biomass). Plant xylem sap phytohormones were measured to determine the plants' physiological status and effects of inoculation treatments. Results revealed that water had a greater effect on plant growth than inoculation treatments. Inoculation treatments, however, improved some physiological parameters. This study suggests that physical conditions such as soil moisture and nutrient availability may occlude more subtle (direct or interactive) effects of beneficial soil microbes on plant growth and plant condition. Prior knowledge on the biological and physicochemical properties of the soil to be amended, and on plant species-specific responses, would be needed to customise microbial inoculants for maximum benefits to ecological restoration, to support future adoption of this practice

    Health behaviors of chinese childhood cancer survivors: A comparison study with their siblings

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    10.3390/ijerph17176136International Journal of Environmental Research and Public Health1717Jan-1

    RNA splicing alterations induce a cellular stress response associated with poor prognosis inAcute Myeloid Leukemia.

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    Purpose: RNA splicing is a fundamental biological process that generates protein diversity from a finite set of genes. Recurrent somatic mutations of splicing factor genes are common in some hematologic cancers but are relatively uncommon in acute myeloid leukemia (AML, < 20% of patients). We examined whether RNA splicing differences exist in AML, even in the absence of splicing factor mutations.Experimental Design: We developed a bioinformatics pipeline to study alternative RNA splicing in RNA-sequencing data from large cohorts of patients with AML.Results: We have identified recurrent differential alternative splicing between patients with poor and good prognosis. These splicing events occurred even in patients without any discernible splicing factor mutations. Alternative splicing recurrently occurred in genes with specific molecular functions, primarily related to protein translation. Developing tools to predict the functional impact of alternative splicing on the translated protein, we discovered that approximately 45% of the splicing events directly affected highly conserved protein domains. Several splicing factors were themselves misspliced and the splicing of their target transcripts were altered. Studying differential gene expression in the same patients, we identified that alternative splicing of protein translation genes in ELNAdv patients resulted in the induction of an integrated stress response and upregulation of inflammation-related genes. Finally, using machine learning techniques, we identified a splicing signature of four genes which refine the accuracy of existing risk prognosis schemes and validated it in a completely independent cohort.Conclusions: Our discoveries therefore identify aberrant alternative splicing as a molecular feature of adverse AML with clinical relevance

    OBITUARY Dr. Ong Jin Eong (August 28, 1943–August 5, 2021)

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    [Extract] Mangroves have lost one of their most ardent and passionate advocates. Dr. Ong Jin Eong, formerly of the Universiti Sains Malaysia (USM) in Penang, passed away at his home on August 5, 2021. Dr. Ong was not only a key figure in Asian mangrove research, management and conservation, his work also attracted significant global recognition. In addition to his research on mangroves and coastal marine ecosystems and his strong advocacy for their conservation, he was responsible for training several thousand students in ecology and coastal management during an academic career spanning three decades

    Restoration ecophysiology: an ecophysiological approach to improve restoration strategies and outcomes in severely disturbed landscapes

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    As human activities destroy and degrade the world's ecosystems at unprecedented scales, there is a growing need for evidence-based methods for ecological restoration if we are to preserve biodiversity and ecosystem services. Mining represents one of the most severe anthropogenic disturbances, often necessitating intensive intervention to restore the most basic attributes of native ecosystems. Despite examples of successful mine-site restoration, re-establishing native vegetation in these degraded landscapes remains a significant challenge. Plant ecophysiology—the study of the interactions between plants and the environment—can provide a useful framework for evaluating and guiding mine-site restoration. By understanding the physiological mechanisms that allow plants to establish and persist in these highly disturbed environments, practitioners may be able to improve restoration outcomes. Specifically, methods in plant ecophysiology can inform site preparation and the selection of plant material for restoration projects, aid in monitoring restoration progress by providing additional insight into plant performance, and ultimately improve our ability to predict restoration trajectories. Here, we review the challenges and benefits of integrating an ecophysiological perspective to mine-site restoration in Western Australia, a global hotspot of biodiversity and mining operations. Using case studies and examples from the region's diverse ecosystems, we illustrate how an ecophysiological approach can guide the restoration of some of the world's most severely disturbed landscapes. With careful selection of study species and traits and consideration of the specific environmental conditions and stressors within a site, the restoration ecophysiology framework outlined here has the potential to inform restoration strategies across ecosystems
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