76 research outputs found
Phosphorylation of HOX11/TLX1 on Threonine-247 during mitosis modulates expression of cyclin B1
RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The HOX11/TLX1 (hereafter referred to as HOX11) homeobox gene was originally identified at a t(10;14)(q24;q11) translocation breakpoint, a chromosomal abnormality observed in 5-7% of T cell acute lymphoblastic leukemias (T-ALLs). We previously reported a predisposition to aberrant spindle assembly checkpoint arrest and heightened incidences of chromosome missegregation in HOX11-overexpressing B lymphocytes following exposure to spindle poisons. The purpose of the current study was to evaluate cell cycle specific expression of HOX11. Results Cell cycle specific expression studies revealed a phosphorylated form of HOX11 detectable only in the mitotic fraction of cells after treatment with inhibitors to arrest cells at different stages of the cell cycle. Mutational analyses revealed phosphorylation on threonine-247 (Thr247), a conserved amino acid that defines the HOX11 gene family and is integral for the association with DNA binding elements. The effect of HOX11 phosphorylation on its ability to modulate expression of the downstream target, cyclin B1, was tested. A HOX11 mutant in which Thr247 was substituted with glutamic acid (HOX11 T247E), thereby mimicking a constitutively phosphorylated HOX11 isoform, was unable to bind the cyclin B1 promoter or enhance levels of the cyclin B1 protein. Expression of the wildtype HOX11 was associated with accelerated progression through the G2/M phase of the cell cycle, impaired synchronization in prometaphase and reduced apoptosis whereas expression of the HOX11 T247E mutant restored cell cycle kinetics, the spindle checkpoint and apoptosis. Conclusions Our results demonstrate that the transcriptional activity of HOX11 is regulated by phosphorylation of Thr247 in a cell cycle-specific manner and that this phosphorylation modulates the expression of the target gene, cyclin B1. Since it is likely that Thr247 phosphorylation regulates DNA binding activity to multiple HOX11 target sequences, it is conceivable that phosphorylation functions to regulate the expression of HOX11 target genes involved in the control of the mitotic spindle checkpoint.Published versio
First identification of long non-coding RNAs in fungal parasite Nosema ceranae
International audienceAbstractNosema ceranae is a unicellular fungal parasite of honey bees and causes huge losses for apiculture. Until present, no study on N. ceranae long non-coding RNAs (lncRNAs) was documented. Here, we sequenced purified spores of N. ceranae using strand-specific library construction and high-throughput RNA sequencing technologies. In total, 83 novel lncRNAs were predicted from N. ceranae spore samples, including lncRNAs, long intergenic non-coding RNAs (lincRNAs), and sense lncRNAs. Moreover, these lncRNAs share similar characteristics with those identified in mammals and plants, such as shorter length and fewer exon number and transcript isoforms than protein-coding genes. Finally, the expression of 12 lncRNAs was confirmed with RT-PCR, confirming their true existence. To our knowledge, this is the first evidence of lncRNAs produced by a microsporidia species, offering novel insights into basic biology such as regulation of gene expression of this widespread taxonomic group
Pseudo attP sites in favor of transgene integration and expression in cultured porcine cells identified by streptomyces phage phiC31 integrase
Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3
Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11–q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11–q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m−/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m−/p+), but not paternal (m+/p−), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone
Low-lying magnetic excitations and magnetocaloric effect of molecular magnet K [V As O (H O)] · 8H O
Low-temperature heat capacity measurements were performed on the molecular nanomagnet (V15). The low-lying magnetic excitations are clearly evidenced by the Schottky anomalies in the specific-heat data. The energy levels determined from the low-temperature observables agree well with the three-spin model for V15. The magnetocaloric effect of V15 is examined. The maximum entropy change of is found for a field change of at . In spite of the low ground-state spin of V15, a drastic entropy change of is observed for a field change of at 0.4 K, which is comparable to the entropy change of some high-spin sub-kelvin magnetic coolers at such low temperatures. Anisotropy and consequent zero-field splitting result in this characteristic of V15 and may open new possibilities in the design of ultra-low-temperature molecular coolers
Generalized Proportional Model of Relay Protection Based on Adaptive Homotopy Algorithm Transient Stability
Relay protection equipment is important to ensure the safe and stable operation of power systems. The risks should be evaluated, which are caused by the failure of relay protection. At present, the fault data and the fault status monitoring information are used to evaluate the failure risks of relay protection. However, there is a lack of attention to the information value of monitoring information in the normal operation condition. In order to comprehensively improve monitoring information accuracy and reduce, a generalized proportional hazard model (GPHM) is established to fully exploit the whole monitoring condition information during the whole operation process, not just the monitoring fault condition data, with the maximum likelihood estimation (MLE) used to estimate the parameters of the GPHM. For solving the nonlinear equation in the process of parameter estimations, the adaptive homotopy algorithm is adopted, which could ensure the reversibility of the Jacobi matrix. Three testing cases have been reviewed, to demonstrate that the adaptive homotopy algorithm is better than traditional algorithms, such as the Newton homotopy algorithm, regarding the calculation speed and convergence. Therefore, GPHM could not only reflect the real time state of the equipment, but also provide a sound theoretical basis for the selection of equipment maintenance types
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