Methylation of TET2, CBL and CEBPA in Ph-negative myeloproliferative neoplasms

A loss-of-function mutation of TET2, CBL and CEBPA has been implicated in the pathogenesis or leukaemic transformation of myeloproliferative neoplasm. As tumour suppressor genes may potentially be inactivated by promoter hypermethylation, the authors studied the methylation status of these genes in three cell lines and diagnostic marrow samples from 45 patients with myeloproliferative neoplasm (MPN) (essential thrombocythaemia, N=34; polycythaemia vera, N=7 and primary myelofibrosis, N=4) by methylation-specific PCR. TET2 was heterozygously methylated in MEG-01 and K562 but completely unmethylated in HEL. On the other hand, both CBL and CEBPA were completely unmethylated in all three cell lines. In the primary marrow samples, methylation of TET2 occurred in two (5.9%) patients with essential thrombocythaemia (4.4% of all patients), both without JAK2 V617 mutation, but not in polycythaemia vera or primary myelofibrosis. There was no association between TET2 methylation with the type of MPN (p=0.713). Hypermethylation of CBL or CEBPA was not detected in any patients. In summary, methylation of TET2, CBL and CEBPA is infrequent in MPN at diagnosis. The role of methylation of these genes at the time of leukaemic transformation warrants further study.published_or_final_versio

Methylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasms

BACKGROUND: MicroRNA (miR) miR-34a, -34b/c, -124-1 and -203 are tumor suppressor miRs implicated in carcinogenesis. METHODS: We studied DNA methylation of these miRs in Philadelphia-negative (Ph-ve) myeloproliferative neoplasms (MPNs). Methylation-specific PCR (MSP), verified by direct sequencing of the methylated MSP products, was performed in cell lines, normal controls and diagnostic marrow samples of patients with MPNs. RESULTS: Methylation of these miRs was absent in the normal controls. miR-34b/c were homozygously methylated in HEL cells but heterozygously in MEG-01. In HEL cells, homozygous miR-34b/c methylation was associated with miR silencing, and 5-aza-2'-deoxycytidine treatment led to re-expression of both miR-34b and miR-34c, consistent with that both miRs are under the regulation of the same promoter CpG island. miR-34a was heterozygously methylated in MEG-01 and K-562. miR-203 was completely unmethylated in K-562 and SET-2 but no MSP amplification was found in both HEL and MEG-01, suggestive of miR deletion. In primary samples, four each had miR-34b/c and -203 methylation, in which two had concomitant methylation of miR-34b/c and -203. miR-34a was methylated in one patient and none had methylation of miR-124-1. Seven patients (15.6%) had methylation of at least one of the four miRs. miR methylation did not correlate with clinical parameters, disease complications or JAK2 V617F mutation. CONCLUSION: This is the first report of miR hypermethylation in MPNs. miR-203 hypermethylation is not specific to Ph+ve leukemias but also present in Ph-ve MPNs. miR-34b/c methylation was associated with reversible miR silencing. There was no correlation of miR methylation with clinical demographic data or outcome.published_or_final_versio

Aberrant p15 gene promoter methylation in therapy-related myelodysplastic syndrome and acute myeloid leukaemia: Clinicopathological and karyotypic associations

Seventeen patients with therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t-MDS/AML) were examined for aberrant p15 gene methylation by methylation-specific polymerase chain reaction. Ten patients (58%) showed p15 methylation, which was significantly related to monosomy/deletion of chromosome 7q, but not to antecedent chemotherapy, blast count, leukaemic evolution or survival. In three of six patients with marrow samples obtained prior to the diagnosis of t-MDS/AML, p15 methylation predated disease development by up to 2 years. Bone marrow transplantation led to the disappearance of p15 methylation in one patient. These results showed that p15 methylation was an early event in the evolution of some t-MDS/AML patients.link_to_OA_fulltex

General Strategy for Broadband Coherent Perfect Absorption and Multi-wavelength All-optical Switching Based on Epsilon-Near-Zero Multilayer Films

We propose a general, easy-to-implement scheme for broadband coherent perfect absorption (CPA) using epsilon-near-zero (ENZ) multilayer films. Specifically, we employ indium tin oxide (ITO) as a tunable ENZ material, and theoretically investigate CPA in the near-infrared region. We first derive general CPA conditions using the scattering matrix and the admittance matching methods. Then, by combining these two methods, we extract analytic expressions for all relevant parameters for CPA. Based on this theoretical framework, we proceed to study ENZ CPA in a single layer ITO film and apply it to all-optical switching. Finally, using an ITO multilayer of different ENZ wavelengths, we implement broadband ENZ CPA structures and investigate multi-wavelength all-optical switching in the technologically important telecommunication window. In our design, the admittance matching diagram was employed to graphically extract not only the structural parameters (the film thicknesses and incident angles), but also the input beam parameters (the irradiance ratio and phase difference between two input beams). We find that the multi-wavelength all-optical switching in our broadband ENZ CPA system can be fully controlled by the phase difference between two input beams. The simple but general design principles and analyses in this work can be widely used in various thin-film devicesopen

Argon milling induced decoherence mechanisms in superconducting quantum circuits

The fabrication of superconducting circuits requires multiple deposition, etch and cleaning steps, each possibly introducing material property changes and microscopic defects. In this work, we specifically investigate the process of argon milling, a potentially coherence limiting step, using niobium and aluminum superconducting resonators as a proxy for surface-limited behavior of qubits. We find that niobium microwave resonators exhibit an order of magnitude decrease in quality-factors after surface argon milling, while aluminum resonators are resilient to the same process. Extensive analysis of the niobium surface shows no change in the suboxide composition due to argon milling, while two-tone spectroscopy measurements reveal an increase in two-level system electrical dipole moments, indicating a structurally altered niobium oxide hosting larger two-level system defects. However, a short dry etch can fully recover the argon milling induced losses on niobium, offering a potential route towards state-of-the-art overlap Josephson junction qubits with niobium circuitry.Comment: Main text: 6 pages, 3 figures, 1 table. 5 appendices, with 6 additional figures and 3 additional tables. 62 reference

A prospective cohort study to investigate parental stress and child health in low-income Chinese families: protocol paper

Introduction Chronic stress has adverse effects on health. Adults and children from low-income families are subject to multiple sources of stress. Existing literature about economic hardship mostly focuses on either adults or children but not both. Moreover, there is limited knowledge on the relationship between parental generalised stress and child health problems. This study aims to explore the bidirectional relationship between parental stress and child health in Chinese low-income families and to identify other modifiable factors influencing this relationship. Methods and analysis This prospective cohort study will sample 254 low-income parent–child pairs and follow them up for 24 months with assessments at three time points (baseline, 12 and 24 months) on parental stress, health-related quality of life (HRQOL) and child health and behaviour using both subjective measures and objective physiological parameters. This study will collect data using standardised measures on HRQOL and behaviours of children as well as on HRQOL, mental health and stress levels of parents along with physiological tests of allostatic load and telomere length. The mediating or moderating effect of family harmony, parenting style and neighbourhood conditions will also be assessed. Data will be analysed using latent growth modelling and cross-lagged path analysis modelling to examine the bidirectional effect of parental stress and child health over time. Mediation and moderation analysis will also be conducted to examine the mechanism by which the variables relate. Ethics and dissemination This study was approved by the institutional review board of the University of Hong Kong—the Hospital Authority Hong Kong West Cluster, reference no: UW 16-415. The study findings will be disseminated through peer-reviewed publications and international conferences.published_or_final_versio