Transcription and pre-mRNA splicing are key steps in the control of gene expression and mutations in genes regulating each of these processes are common in leukaemia
. Despite the frequent overlap of ...mutations affecting epigenetic regulation and splicing in leukaemia, how these processes influence one another to promote leukaemogenesis is not understood and, to our knowledge, there is no functional evidence that mutations in RNA splicing factors initiate leukaemia. Here, through analyses of transcriptomes from 982 patients with acute myeloid leukaemia, we identified frequent overlap of mutations in IDH2 and SRSF2 that together promote leukaemogenesis through coordinated effects on the epigenome and RNA splicing. Whereas mutations in either IDH2 or SRSF2 imparted distinct splicing changes, co-expression of mutant IDH2 altered the splicing effects of mutant SRSF2 and resulted in more profound splicing changes than either mutation alone. Consistent with this, co-expression of mutant IDH2 and SRSF2 resulted in lethal myelodysplasia with proliferative features in vivo and enhanced self-renewal in a manner not observed with either mutation alone. IDH2 and SRSF2 double-mutant cells exhibited aberrant splicing and reduced expression of INTS3, a member of the integrator complex
, concordant with increased stalling of RNA polymerase II (RNAPII). Aberrant INTS3 splicing contributed to leukaemogenesis in concert with mutant IDH2 and was dependent on mutant SRSF2 binding to cis elements in INTS3 mRNA and increased DNA methylation of INTS3. These data identify a pathogenic crosstalk between altered epigenetic state and splicing in a subset of leukaemias, provide functional evidence that mutations in splicing factors drive myeloid malignancy development, and identify spliceosomal changes as a mediator of IDH2-mutant leukaemogenesis.
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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
Abstract
The questions of how the bulk of the Universe’s visible mass emerges and how it is manifest in the existence and properties of hadrons are profound, and probe the heart of strongly ...interacting matter. Paradoxically, the lightest pseudoscalar mesons appear to be key to a further understanding of the emergent mass and structure mechanisms. These mesons, namely, the pion and kaon, are the Nambu–Goldstone boson modes of quantum chromodynamics (QCD). Unravelling their partonic structure and the interplay between emergent and Higgs-boson mass mechanisms is a common goal of three interdependent approaches—continuum QCD phenomenology, lattice-regularised QCD, and the global analysis of parton distributions—linked to experimental measurements of hadron structure. Experimentally, the anticipated electron–ion collider will enable a revolution in our ability to study pion and kaon structures, accessed by scattering from the ‘meson cloud’ of the proton through the Sullivan process. With the goal of enabling a suite of measurements that can address these questions, we examine key reactions that identify the critical detector-system requirements needed to map tagged pion and kaon cross-sections over a wide range of kinematics. The excellent prospects for extracting pion structural, functional, and form-factor data are outlined, and similar prospects for kaon structures are discussed in the context of a worldwide programme. The successful completion of the programme outlined herein will deliver deep, far-reaching insights into the emergence of pions and kaons, their properties, and their role as QCD’s Goldstone boson modes.
The aim of this work was to determine the magnitude of the priming effect,
i.e. short-term changes in the rate (negative or positive) of mineralisation of native soil organic carbon (C), following ...addition of biochars. The biochars were made from
Miscanthus giganteus, a C4 plant, naturally enriched with
13C. The biochars were produced at 350 °C (biochar350) and 700 °C (biochar700) and applied with and without ryegrass as a substrate to a clay-loam soil at pH 3.7 and 7.6. A secondary aim was to determine the effect of ryegrass addition on the mineralisation of the two biochars.
After 87 days, biochar350 addition caused priming effects equivalent to 250 and 319 μg CO
2–C g
−1 soil, in the low and high pH soil, respectively. The largest priming effects occurred at the start of the incubations. The size of the priming effect was decreased at higher biochar pyrolysis temperatures, which may be a way of controlling priming effects following biochar incorporation to soil, if desired. The priming effect was probably induced by the water soluble components of the biochar. At 87 days of incubation, 0.14% and 0.18% of biochar700 and 0.61% and 0.84% of biochar350 were mineralized in the low and high pH soil, respectively. Ryegrass addition gave an increased biochar350 mineralisation of 33% and 40%, and increased biochar700 at 137% and 70%, in the low and high pH soils, respectively. Certainly, on the basis of our results, if biochar is used to sequester carbon a priming effect may occur, increasing CO
2–C evolved from soil and decreasing soil organic C. However, this will be more than compensated for by the increased soil C caused by biochar incorporation. A similar conclusion holds for accelerated mineralisation of biochar due to incorporation of fresh labile substrates. We consider that our results are the first to unequivocally demonstrate the initiation, progress and termination of a true positive priming effect by biochar on native soil organic C.
► Priming effects on soil organic matter following incorporation of biochar to soil. ► Detecting the interactions between biochar and soil pH. ► Enhanced biochar mineralisation following substrate addition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
SETTING: Risk of pneumonia in chronic obstructive pulmonary disease (COPD) patients due to comorbid pulmonary disease is not well understood.OBJECTIVE: To compare factors associated with risk of ...community-acquired pneumonia (CAP) in COPD patients for those with and without lung
cancer, bronchiectasis and/or history of active tuberculosis.DESIGN: Retrospective chart review of patients diagnosed with COPD (forced expiratory volume in 1 second/forced vital capacity < 0.70) between 2006 and 2010, including patient characteristics, occurrence of CAP and type of
inhalation treatment. Pneumonia-free survivals were assessed using Kaplan-Meier curves. Factors associated with CAP were assessed using Cox's proportional hazard regression and expressed as adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).RESULTS: Of 2630 patients, 402
(15.3%) developed CAP during follow-up. The likelihood of CAP increased with increased age (aHR 1.03, 95%CI 1.02-1.04), lower body mass index (BMI; aHR 0.97, 95%CI 0.95-1.00), lung cancer (aHR 3.81, 95%CI 2.88-5.05), bronchiectasis (aHR 2.46, 95%CI 1.70-3.55) and inhaled
corticosteroid (ICS) containing treatment (aHR 1.60, 95%CI 1.30-1.96). ICS-containing treatment was associated with increased risk of CAP only for patients without comorbid pulmonary disease (aHR 1.68, 95%CI 1.30-2.17).CONCLUSION: For COPD patients: 1) increased age, low BMI,
lung cancer and bronchiectasis may increase the risk of CAP, and 2) without respiratory comorbid disease, ICS use increases the risk of CAP.
A hierarchical unmanned aircraft system (UAS) traffic management (UTM) system has deployed 45 ground transceiver stations (GTS) for UAS services in Taiwan. This UTM system covers most areas for ...UAV-dependent surveillance using ADS-B Like technology. UTM Controller can monitor all UAV flights under transparent surveillance in low airspace. Controller-initiated UAV “detect and avoid” (DAA) mechanism assists UAV separation to ensure flight safety on UTM for small multirotor UAVs. From similar concept to traffic alert and collision avoidance system (TCAS) for the manned aircraft system, the UTM software executes DAA functions to generate approach alerts to UTM Controller. Conflict is detected by heading arrow extrapolation from multiple approaching UAVs by their time to conflict (TTC) on icons. Traffic advisory (TA) and resolution advisory (RA) are pronounced on UTM console to controllers. The less priority UAV pilot will receive the controller-pilot communication (CPC) to perform avoidance resolution. In UTM, the surveillance data period is broadcasting at 5~8 seconds on LoRa (long-range wide-area network) chip. Referring to TA=48 seconds and RA=24 seconds, the signal delay in ADS-B Like system to UTM server is about 0.5 seconds and CPC response is measured about 3~5 seconds. From real flight tests, the RA is enough for the less priority pilot to maneuver UAV for avoidance. From real flight tests, the proposed DAA mechanism based on UTM-dependent surveillance is feasible to resolve multiple approaches. The developing UTM system using ADS-B Like technology is also examined of high availability with redundant reliability and performance stability for flight safety.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Chicken infectious anaemia (CIA) is a disease with a highly economic impact in the poultry industry. The infected chickens are characterized by aplastic anaemia and extreme immunosuppression, ...followed by the increased susceptibility to secondary infectious pathogens and suboptimal immune responses for vaccination. Commercially available CIA vaccines are routinely used in the breeders in Taiwan to protect their progeny with maternal‐derived antibodies. However, CIA cases still occur in the field and little is known about the genetic characteristics of Taiwanese chicken anaemia viruses (CAVs). In this study, CAV DNA was detected in 72 of 137 flocks collected during 2010–2015. Among the PCR‐positive samples, the coding regions of 51 CAVs were sequenced. Phylogenetic analysis of the VP1 gene revealed that, although most of Taiwanese CAVs belonged to genotypes II and III, some isolates were clustered into a novel genotype (genotype IV). Moreover, a Taiwanese isolate in this novel genotype IV appeared to be derived from a recombination event between genotypes II and III viruses. Five Taiwanese CAV isolates were highly similar to the vaccine strains, 26P4 or Del‐Ros. Taken together, these results indicate that the sequences of CAVs in Taiwan are variable, and inter‐genotypic recombination had occurred between viruses of different genotypes. Moreover, vaccine‐like strains might induce clinical signs of CIA in chickens. Our findings could be useful for understanding the evolution of CAVs and development of a better control strategy for CIA.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Intracranial germinoma (IG) rarely occurs in adults. Its optimal treatment strategy is unclear. We evaluated the outcomes of radiotherapy in adults with intracranial germinoma. Data of 29 adult ...patients (age, 18-52 years; median age, 24.3 years) with IG treated with radiotherapy at Taipei Veterans General Hospital were retrospectively reviewed. They were followed up for a median time of 5.9 years (range, 1.0-12.8 years). We used the Kaplan-Meier method to estimate the progression-free survival (PFS) and overall survival (OS), and univariate and multivariate Cox proportional hazards regression models to identify the factors affecting PFS. PFS and OS were compared between adult and pediatric patients with IG. The 1-, 3-, and 5-year PFS rates were 96.6%, 85.8%, and 77.8%, respectively, in the adult patients, and the OS rate were all 100%. Seven patients (24.1%) experienced recurrence, and in six of them, salvage therapy successfully controlled the disease. Two patients (6.9%) died after 5 years of follow-up due to disease progression and central pontine myelinolysis. In the univariate and multivariate Cox analysis, bifocal lesions had a significantly lower PFS than those with single lesions (p = 0.008). Kaplan-Meier survival analysis showed that adult patients had a poorer PFS (p = 0.06) and OS (p = 0.025) than pediatric patients. Our study showed bifocal lesions were associated with lower PFS than a single lesion among adult IG patients, and adult IG patients tended to have poorer PFS and OS compared to pediatric IG patients. For adult patients with bifocal IG, we recommend treatment with craniospinal irradiation, whole ventricle irradiation (WVI) with chemotherapy, or frequent spine images follow-up for patients who received only WVI.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report a study of X-ray emission from the white dwarf/M-type star binary system AR Scorpii using archival data taken in 2016-2020. It has been known that the X-ray emission is dominated by ...optically thin thermal plasma emission and its flux level varies significantly over the orbital phase. The X-ray emission also contains a component that modulates with the beat frequency between the white dwarf's spin frequency and orbital frequency. In this new analysis, the 2020 data taken by NICER shows that the X-ray emission modulates with the spin frequency as well as with the beat frequency, indicating that part of the X-ray emission comes from the white dwarf's magnetosphere. It is found that the signal of the spin frequency appears only at a specific orbital phase, while the beat signal appears over the orbital phase. We interpret the X-ray emission modulating with the spin frequency and the beat frequency as a result of synchrotron emission from electrons with smaller and larger pitch angles, respectively. In the long-term evolution, the beat pulse profile averaged over the orbital phase changes from a single-peak structure in 2016/2018 to a double-peak structure in 2020. The observed X-ray flux levels measured in 2016/2017 are higher than those measured in 2018/2020. The plasma temperature and the amplitude of the orbital waveform might vary with time too. These results indicate that the X-ray emission from AR Scorpii evolves on a timescale of years. This long-term evolution would be explained by a superorbital modulation related to, for example, a precession of the white dwarf or a fluctuation of the system related to the activity of the companion star.
MicroRNA in lung cancer LIN, P.-Y; YU, S.-L; YANG, P.-C
British journal of cancer,
10/2010, Volume:
103, Issue:
8
Journal Article
Peer reviewed
Open access
MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as endogenous negative gene regulators. Dysfunctions of miRNAs are frequently found in malignancies, including lung cancer. In this ...review, we summarise the current understanding of miRNAs in lung cancer tumourigenesis, and highlight their potential in overcoming drug resistance, abetting histological sub-classification techniques, and serving as biomarkers for lung cancer risk stratification and outcome prediction.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation, producing carbon monoxide (CO), which carries potent antiproliferative and anti-inflammatory effects in the vascular walls. ...Transcription of the HO-1 gene is regulated by the length polymorphism of dinucleotide guanosine thymine repeat (GT)n in the promoter region, which was measured in this study to determine its association with arteriovenous fistula (AVF) failure in Chinese hemodialysis (HD) patients in Taiwan. L allele means (GT)n≥30 and S allele means (GT)n<30. Therefore, there are two L alleles for L/L genotype, one L and one S allele for L/S genotype, and two S alleles for S/S genotype. Among the 603 HD patients who were enrolled in this study, 178 patients had history of AVF failure, while 425 patients did not. Significant associations were found between AVF failure and the following factors (hazard ratio): longer HD duration (1.004 month), lower pump flow (0.993 ml/min), higher dynamic venous pressure (1.010 mmHg), location of AVF on the right side (1.587 vs left side) and upper arm (2.242 vs forearm), and L/L and L/S genotypes of HO-1 (2.040 vs S/S genotype). The proportion of AVF failure increased from 20.3% in S/S genotype and 31.0% in L/S genotype to 35.4% in L/L genotype (P=0.011). Relative incidences were 1/87.6 (1 episode per 87.6 patient-months), 1/129, and 1/224.9 for HD patients with L/L, L/S, and S/S genotypes, respectively (P<0.002). The unassisted patency of AVF at 5 years decreased significantly from 83.8% (124/148) to 75.1% (223/297) and 69% (109/158) in S/S, L/S, and L/L genotypes, respectively (P<0.0001). In comparison with HD patients with S/S genotype, those with L/L genotype had a higher prevalence of coronary artery disease (29.1 vs 14.2%; P=0.005). A longer length polymorphism with (GT)n ≥30 in the HO-1 gene was associated with a higher frequency of access failure and a poorer patency of AVF in HD patients. The longer GT repeat in the HO-1 promoter might inhibit gene transcription, and consequently offset the CO-mediated protective effect against vascular injury.
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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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