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  • 11
    Publication Date: 2013-03-23
    Description: Aims Ageing of the immune system, immunosenescence, is characterized by impaired lymphopoiesis, especially B-lymphocyte maturation, and is a hallmark of chronic heart failure (CHF). MicroRNAs (miRNAs) are non-coding, small RNAs, which post-transcriptionally control gene expression of multiple target genes. The miR-181 family is known to control haematopoietic lineage differentiation. Here, we study the role of the miR-181 family in immunosenescence and CHF. Methods and results We conducted a clinical study analysing peripheral blood (PB) for miRNA expression and leucocyte distribution of young healthy controls (25 ± 4 years; n = 30), aged healthy controls (64 ± 5 years; n = 13), and age-matched CHF patients (64 ± 11years; n = 18). The expression of miR-181 family members was reduced, whereas miR-34a was increased in PB of aged individuals. In particular, miR-181c was further reduced in age-matched CHF patients. In PB, we observed reduced numbers of lymphocytes, in particular cytotoxic T cells and B cells, with rising age, and the expression of miR-181 correlated with the number of B cells. Notably, in CHF patients, ischaemic heart failure was associated with a further reduction of total B cells as well as their subpopulations, such as memory B cells, compared with age-matched healthy volunteers. Conclusions Ageing- and CHF-associated changes in PB leucocyte subsets are paralleled by alterations in the expression of miRNAs involved in lymphopoiesis, which might play an important role in the age-related and CHF-mediated dysregulation of immune functions resulting in immunosenescence. Furthermore, miR-181c may serve as a marker for reduced immune functions in CHF patients.
    Print ISSN: 1388-9842
    Electronic ISSN: 1879-0844
    Topics: Medicine
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  • 12
    Publication Date: 2018-05-04
    Description: The transcription factor "nuclear factor erythroid 2" (NFE2) is overexpressed in the majority of patients with myeloproliferative neoplasms (MPNs). In murine models, elevated NFE2 levels cause an MPN phenotype with spontaneous leukemic transformation. However, both the molecular mechanisms leading to NFE2 overexpression and its downstream targets remain incompletely understood. Here, we show that the histone demethylase JMJD1C constitutes a novel NFE2 target gene. JMJD1C levels are significantly elevated in polycythemia vera (PV) and primary myelofibrosis patients; concomitantly, global H3K9me1 and H3K9me2 levels are significantly decreased. JMJD1C binding to the NFE2 promoter is increased in PV patients, decreasing both H3K9me2 levels and binding of the repressive heterochromatin protein-1α (HP1α). Hence, JMJD1C and NFE2 participate in a novel autoregulatory loop. Depleting JMJD1C expression significantly reduced cytokine-independent growth of an MPN cell line. Independently, NFE2 is regulated through the epigenetic JAK2 pathway by phosphorylation of H3Y41. This likewise inhibits HP1α binding. Treatment with decitabine lowered H3Y41ph and augmented H3K9me2 levels at the NFE2 locus in HEL cells, thereby increasing HP1α binding, which normalized NFE2 expression selectively in JAK2 V617F -positive cell lines.
    Keywords: Myeloid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 13
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    In:  XXVIII General Assembly of the International Union of Geodesy and Geophysics (IUGG)
    Publication Date: 2023-12-12
    Description: Instituto Português do Mar e da Atmosfera (IPMA) operates an observatory in São Teotónio, Alentejo Region, Portugal, for seismic, magnetic and other observations. This observatory also provides ideal conditions to operate an INTERMAGNET-type geomagnetic observatory, including a nonmagnetic underground building for a variometer and a non-magnetic building for absolute measurements. In May 2019, IPMA and Observatory Niemegk/GFZ Potsdam installed a Geomag 01 variometer loaned from GFZ's instrument pool. For absolute measurements, a Mingeo 010 theodolite and a GSM-19 scalar magnetometer is used. Additionally, a Geometrics G-862RBS cesium magnetometer is recording geomagnetic field strength with 10 Hz. With some intermediate modifications, the Geomag 01 magnetometer was used until July 2022, and sometimes electric field was also measured at the observatory. In July 2022, a FGE variometer with two analogue outputs and two data loggers and a GSM-90 scalar magnetometer was installed. The new loggers have real-time capability and the whole system is supported by a uninterruptible power supply. In spring 2023, we plan to apply for INTERMAGET participation. Here, we describe the various observatory setups and the recordings collected since May 2019 and bring them into context with other observatory time series from the Iberian Peninsula.
    Language: English
    Type: info:eu-repo/semantics/conferenceObject
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