MicroRNAs (miRNAs) regulate the expression of multiple proteins in a dose-dependent manner. We hypothesized that increased expression of miRNAs encoded on chromosome 21 (chr 21) contribute to the ...leukemogenic function of trisomy 21. The levels of chr 21 miRNAs were quantified by qRT-PCR in four types of childhood acute lymphoblastic leukemia (ALL) characterized by either numerical (trisomy or tetrasomy) or structural abnormalities of chr 21. Suprisingly, high expression of the hsa-mir-125b-2 cluster, consisting of three miRNAs, was identified in leukemias with the structural ETV6/RUNX1 abnormality and not in ALLs with trisomy 21. Manipulation of ETV6/RUNX1 expression and chromatin immunoprecipitation studies showed that the high expression of the miRNA cluster is an event independent of the ETV6/RUNX1 fusion protein. Overexpression of hsa-mir-125b-2 conferred a survival advantage to Ba/F3 cells after IL-3 withdrawal or a broad spectrum of apoptotic stimuli through inhibition of caspase 3 activation. Conversely, knockdown of the endogenous miR-125b in the ETV6/RUNX1 leukemia cell line REH increased apoptosis after Doxorubicin and Staurosporine treatments. P53 protein levels were not altered by miR-125b. Together, these results suggest that the expression of hsa-mir-125b-2 in ETV6/RUNX1 ALL provides survival advantage to growth inhibitory signals in a p53-independent manner.
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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, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The reciprocal translocation t(12;21)(p13;q22), the most common structural genomic alteration in B-cell precursor acute lymphoblastic leukaemia in children, results in a chimeric transcription factor ...TEL-AML1 (ETV6-RUNX1). We identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with chromatin immunoprecipitation (ChIP)-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture, we identified 217 directly and 118 indirectly regulated targets of the TEL-AML1 fusion protein. Directly, but not indirectly, regulated promoters were enriched in AML1-binding sites. The majority of promoter regions were specific for the fusion protein and not bound by native AML1 or TEL. Comparison with gene expression profiles from TEL-AML1-positive patients identified 56 concordantly misregulated genes with negative effects on proliferation and cellular transport mechanisms and positive effects on cellular migration, and stress responses including immunological responses. In summary, this work for the first time gives a comprehensive insight into how TEL-AML1 expression may directly and indirectly contribute to alter cells to become prone for leukemic transformation.
The chromosomal translocation t(8;14) is the hallmark of Burkitt's-lymphoma (BL) and fuses the proto-oncogene c-MYC to the IGH locus. We analyzed the genomic structure of MYC/IGH fusions derived from ...a large series of 78 patients with t(8;14) and asked (i) whether distinct breakpoint clusters exist within the MYC gene and (ii) whether any pairwise association between particular IGH and MYC breakpoints exist. Identification of such associations will help elucidate the etiology of the breaks on the MYC locus. Scan statistic analyses revealed two distinct, but large clusters within c-MYC containing 60/78 (77%) of the breakpoints. Clusters 1 and 2 were 560 and 779 bp in length within a 4555 bp breakpoint cluster region. Breaks within IGH switch mu and joining region did not differ with respect to their corresponding MYC breakpoints. However, there was a highly significant correlation between breakpoints 5' of MYC cluster 1 and fusions to IGH switch gamma region and breakpoints downstream of MYC cluster 2 and fusions to IGH switch alpha region (chi(2)-test: P<0.005). Chromatin changes governing choice of IGH-Fc region recombination may parallel changes in the MYC gene 5' region chromatin leading to some degree of coordinated ontological specificity in breakpoint location.
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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, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
MicroRNAs (miRNAs) are small noncoding regulatory RNAs that reduce stability and/or translation of fully or partially sequence-complementary target mRNAs. In order to identify miRNAs and to assess ...their expression patterns, we sequenced over 250 small RNA libraries from 26 different organ systems and cell types of human and rodents that were enriched in neuronal as well as normal and malignant hematopoietic cells and tissues. We present expression profiles derived from clone count data and provide computational tools for their analysis. Unexpectedly, a relatively small set of miRNAs, many of which are ubiquitously expressed, account for most of the differences in miRNA profiles between cell lineages and tissues. This broad survey also provides detailed and accurate information about mature sequences, precursors, genome locations, maturation processes, inferred transcriptional units, and conservation patterns. We also propose a subclassification scheme for miRNAs for assisting future experimental and computational functional analyses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Belle II experiment at the SuperKEKB electron–positron collider aims to collect an unprecedented data set of 50ab−1 to study CP-violation in the B-meson system and to search for Physics beyond ...the Standard Model. SuperKEKB is already the world’s highest-luminosity collider. In order to collect the planned data set within approximately one decade, the target is to reach a peak luminosity of 6 × 1035cm−2s−1 by further increasing the beam currents and reducing the beam size at the interaction point by squeezing the betatron function down to βy∗=0.3mm. To ensure detector longevity and maintain good reconstruction performance, beam backgrounds must remain well controlled. We report on current background rates in Belle II and compare these against simulation. We find that a number of recent refinements have significantly improved the background simulation accuracy. Finally, we estimate the safety margins going forward. We predict that backgrounds should remain high but acceptable until a luminosity of at least 2.8 × 1035cm−2s−1 is reached for βy∗=0.6mm. At this point, the most vulnerable Belle II detectors, the Time-of-Propagation (TOP) particle identification system and the Central Drift Chamber (CDC), have predicted background hit rates from single-beam and luminosity backgrounds that add up to approximately half of the maximum acceptable rates.
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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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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
7.
Croatia has reached iodine sufficiency KUSIC, Z; NOVOSEL, S. A; MESAROS-KANJSKI, E ...
Journal of endocrinological investigation,
08/2003, Volume:
26, Issue:
8
Journal Article
Peer reviewed
This study was performed in 2002, 6 yr after the introduction of a new regulation on salt iodination with 25 mg KI/kg of salt. The aim of the study was to evaluate whether further significant ...positive results of improved iodine intake could be observed among schoolchildren in Croatia. A total of 927 schoolchildren of both sexes, aged 6-12 yr, were included in the study. In Croatia, with a population of 4,437,460 the research was implemented in four major geographical regions: the Northwestern, Slavonia, Northern Adriatic and Dalmatian regions. Investigations included randomly selected pupils from regional centers and neighboring smaller towns or villages. The results have revealed that thyroid volumes were within the normal range according to the provisional WHO/ICCIDD reference values for sonographic thyroid volume in iodine-replete school-age children, updated in 2001. A significant improvement in medians of urinary iodine excretion was detected in 2002: from 9 microg/dl in 1991 to 14.6 microg/dl in Zagreb, from 4.3 microg/dl in 1995 to 13.1 microg/dl in Split, from 9.4 microg/dl in 1997 to 14.2 microg/dl in Rijeka and from 13.4 microg/dl in 1997 to 14.7 microg/dl in Osijek. An overall median of 14.0 microg/dl of urinary iodine excretion was detected in Croatian schoolchildren. The control of salt at different levels, from production to consumption, including salt produced in all three Croatian salt plants and imported salt, revealed that Croatian salt is adequately iodized. From severe iodine deficiency before the 1950s, through mild-to-moderate iodine deficiency in the 1990s, Croatia has now reached iodine sufficiency.
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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
A 46-year-old woman with clinical diagnosis of Riedel's thyroiditis was admitted to our Department, presenting with dyspnea, dysphagia, fatigue, and hoarseness. Previously, she had been diagnosed ...with Hashimoto's thyroiditis and hypothyroidism. The disease had a progressive course and had lasted for a year before the definitive diagnosis of Riedel's thyroiditis was confirmed and treated with methylprednisolone, 12 mg daily, without success. We started therapy with tamoxifen, 10 mg twice a day, together with methylprednisolone, 16 mg daily, and L-thyroxin substitution therapy. The follow-up lasted for one year. Treatment with tamoxifen led to a significant subjective improvement and objective changes, confirmed by regular clinical examinations, ultrasonography, and computed tomography of the neck. After 8 months of therapy, the patient had no compression symptoms and goiter decreased in estimated weight from 105 g to 63 g according to ultrasound measurements. The patient underwent partial thyroidectomy at 10 months after diagnosis of Riedel's thyroiditis. Histopathology confirmed the diagnosis of Riedel's thyroiditis. Our report indicates that tamoxifen can be a valuable drug therapy in the treatment of Riedel's thyroiditis.
In this study, regression equations (prediction equations) were established for the purpose of accurately predicting the widths of the crowns of unerupted canines (C) and premolars (P1 and P2) on the ...basis of the measured mesiodistal diameter (MDD) and vestibulooral diameter (VOD) of the crowns of the erupted central and lateral incisors (I1, I2) and first permanent molars (M1). On the plaster casts of 120 subjects (60 boys and 60 girls), MDD and VOD of the crowns of I1, I2, C, both P1 and P2, and M1 on both sides in both jaws were measured twice, with a time distance between measurements. Gradual regression equations were derived on the basis of the measurement results, by which the sums of the widths of crowns of C, P1, and P2 can be predicted using three to five predictors. The coefficients of multiple correlations regarding the sex and the jaw varied from 0.79 to 0.85.
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