TCEA1 regulates the proliferative potential of mouse myeloid cells.

Leukemia is a malignance with complex pathogenesis and poor prognosis. Discovery of noval regulators amenable to leukemia could be of value to gain insight into the pathogenesis, diagnosis and prognosis of leukemia. Here, we conducted a large-scale shRNA library screening for functional regulators in the development of myeloid cells in primary cells. We identified eighteen candidate regulators in the primary screening. Those genes cover a wide range of cellular functions, including gene expression regulation, intracellular signaling transduction, nucleotide excision repair, cell cycle control and transcription regulation. In both primary screening and validation, shRNAs targeting Tcea1, encoding the transcription elongation factor A (SII) 1, exhibited the greatest influence on the proliferative potential of cells. Knocking down the expression of Tcea1 in the 32Dcl3 myeloid cell line led to enhanced proliferation of myeloid cells and blockage of myeloid differentiation induced by G-CSF. In addition, silence of Tcea1 inhibited apoptosis of myeloid cells. Thus, Tcea1 was identified as a gene which can influence the proliferative potential, survival and differentiation of myeloid cells. These findings have implications for how transcriptional elongation influences myeloid cell development and leukemic transformation

TCEA1 regulates the proliferative potential of mouse myeloid cells.

Leukemia is a malignance with complex pathogenesis and poor prognosis. Discovery of noval regulators amenable to leukemia could be of value to gain insight into the pathogenesis, diagnosis and prognosis of leukemia. Here, we conducted a large-scale shRNA library screening for functional regulators in the development of myeloid cells in primary cells. We identified eighteen candidate regulators in the primary screening. Those genes cover a wide range of cellular functions, including gene expression regulation, intracellular signaling transduction, nucleotide excision repair, cell cycle control and transcription regulation. In both primary screening and validation, shRNAs targeting Tcea1, encoding the transcription elongation factor A (SII) 1, exhibited the greatest influence on the proliferative potential of cells. Knocking down the expression of Tcea1 in the 32Dcl3 myeloid cell line led to enhanced proliferation of myeloid cells and blockage of myeloid differentiation induced by G-CSF. In addition, silence of Tcea1 inhibited apoptosis of myeloid cells. Thus, Tcea1 was identified as a gene which can influence the proliferative potential, survival and differentiation of myeloid cells. These findings have implications for how transcriptional elongation influences myeloid cell development and leukemic transformation

Duloxetine-induced rapid eye movement sleep behavior disorder: a case report

Abstract Background Tricyclic antidepressants and selective serotonin reuptake inhibitors have been reported to induce the symptoms of rapid eye movement (REM) sleep behavior disorder (RBD) or to exacerbate REM sleep without atonia. With this case report, we found an association between typical RBD and duloxetine, a serotonin-noradrenaline reuptake inhibitor. Case presentation We present a case of a 62-year-old woman who experienced enactment behaviors with violent dreams that were associated with increased tonic or phasic chin electromyography activity during REM sleep after treated with duloxetine. RBD symptoms were gradually reduced and completely ceased after discontinuation of duloxetine for 37 days. Conclusion The current case appears to be the first observation of duloxetine-induced RBD. We describe features of RBD induced by duloxetine that are similar and different from that induced by tricyclic antidepressants and selective serotonin reuptake inhibitors

The neural substrates for atypical planning and execution of word production in stuttering.

Using an fMRI-based classification approach and the structural equation modeling (SEM) method, this study examined the neural bases of atypical planning and execution processes involved in stuttering. Twelve stuttering speakers and 12 controls were asked to name pictures under different conditions (single-syllable, multi-syllable, or repeated-syllable) in the scanner. The contrasts between conditions provided information about planning and execution processes. The classification analysis showed that, as compared to non-stuttering controls, stuttering speakers' atypical planning of speech was evident in their neural activities in the bilateral inferior frontal gyrus (IFG) and right putamen and their atypical execution of speech was evident in their activations in the right cerebellum and insula, left premotor area (PMA), and angular gyrus (AG). SEM results further revealed two parallel neural circuits-the basal ganglia-IFG/PMA circuit and the cerebellum-PMA circuit-that were involved in atypical planning and execution processes of stuttering, respectively. The AG appeared to be involved in the interface of atypical planning and execution in stuttering. These results are discussed in terms of their implications to the theories about stuttering and to clinical applications

The neural substrates for atypical planning and execution of word production in stuttering.

Using an fMRI-based classification approach and the structural equation modeling (SEM) method, this study examined the neural bases of atypical planning and execution processes involved in stuttering. Twelve stuttering speakers and 12 controls were asked to name pictures under different conditions (single-syllable, multi-syllable, or repeated-syllable) in the scanner. The contrasts between conditions provided information about planning and execution processes. The classification analysis showed that, as compared to non-stuttering controls, stuttering speakers' atypical planning of speech was evident in their neural activities in the bilateral inferior frontal gyrus (IFG) and right putamen and their atypical execution of speech was evident in their activations in the right cerebellum and insula, left premotor area (PMA), and angular gyrus (AG). SEM results further revealed two parallel neural circuits-the basal ganglia-IFG/PMA circuit and the cerebellum-PMA circuit-that were involved in atypical planning and execution processes of stuttering, respectively. The AG appeared to be involved in the interface of atypical planning and execution in stuttering. These results are discussed in terms of their implications to the theories about stuttering and to clinical applications

Involvement of CUL4A in Regulation of Multidrug Resistance to P-gp Substrate Drugs in Breast Cancer Cells

CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described in this report we aimed to clarify whether CUL4A participates in multiple drug resistance (MDR) in breast cancer cells. We first transfected vectors carrying CUL4A and specific shCUL4A into breast cancer cells and corresponding Adr cells respectively. Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1/P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. On the other hand, silencing CUL4A in MCF7/Adr and MDA-MB-468/Adr cells led to the opposite effect. Moreover, ERK1/2 in CUL4A-overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A-induced expression of MDR1/P-gp was decreased significantly. Lastly, immunohistochemistry in breast cancer tissues showed that P-gp expression had a positive correlation with the expression of CUL4A and ERK1/2. Thus, these results implied that CUL4A and ERK1/2 participated in multi-drug resistance in breast cancer through regulation of MDR1/P-gp expression