China
Africa
Explore chapters and articles related to this topic
Blastic Transformation of Chronic Myelogenous Leukemia: Does BCR-ABL Orchestrate Disease Progression?
Published in Jorge Cortes, Michael Deininger, Chronic Myeloid Leukemia, 2006
Calabretta Bruno, Perrotti Danilo
The oncogene MYC was one of the first identified BCR-ABL targets required for BCR-ABL leukemogenesis (46,47). Although in some blast crisis CML patients the MYC gene is amplified (2), several BCR-ABL-dependent mechanisms seem to enhance MYC expression at the transcriptional, translational, or post-translational level (39,46,48–51). One of the BCR-ABL pathways regulating MYC expression involves the KH-domain RNA binding protein HNRPK (hnRNP K) (39), a known transcriptional and translational regulator of gene expression (refer ref. 39 and the references therein).
Can trophectoderm RNA analysis predict human blastocyst competency?
Published in Systems Biology in Reproductive Medicine, 2019
Panagiotis Ntostis, Georgia Kokkali, David Iles, John Huntriss, Maria Tzetis, Helen Picton, Konstantinos Pantos, David Miller
The edgeR exact test was used to reveal significantly differentially expressed (DE) transcripts between competent and incompetent blastocysts (Figure 1; please see Μaterials and Μethods supplementary file for full details). The DE transcripts belonged to 47 unique genes (Table 1). Given that the competent group represents normal TE expression levels, the current study focused on the significantly lower/higher expression levels of the incompetent blastocysts. Following normalization of the RNA sequencing results, 36 transcripts were found to be significantly down-regulated in these blastocysts with the remainder being up-regulated (FDR < 0.05). These included KH Domain Containing 1 Pseudogene 1 (KHDC1P1), the apoptosis regulator BCL2 Antagonist/Killer 1 (BAK1), suggesting a potentially significant regulatory function perhaps relating to an underlying apoptotic process. All DE transcripts had at least three-fold-change, apart from KH RNA Binding Domain Containing, Signal Transduction Associated 3 (KHDRBS3) and Emopamil Binding Protein (Sterol Isomerase; EBP) that were slightly lower at 2.7-fold.
Platelets as a surrogate disease model of neurodevelopmental disorders: Insights from Fragile X Syndrome
Published in Platelets, 2018
David Pellerin, Audrey Lortie, François Corbin
Fragile X Syndrome is the leading inherited monogenic cause of ID and ASD, affecting approximately 1 in 4,000 males and 1 in 8,000 females [23]. The clinical phenotype is further characterized by a wide array of behavioral, neuropsychiatric and physical characteristics, such as epilepsy, attention deficit hyperactivity disorder, macroorchidism and connective tissue anomalies (i.e., hyper-extendible joints, flat feet, high-arched palate) [1,24]. About 30% of FXS males meet diagnostic criteria for ASD and among those who do not, 90% present autistic features [25,26]. Almost all cases of FXS (>98%) result from the absence of expression of the fragile X mental retardation protein (FMRP) caused by a CGG trinucleotide-repeat expansion in the 5ʹ-untranslated region of the fragile X mental retardation 1 (FMR1) gene along with the methylation of its promoter [27,28]. Aside from cardiac and skeletal striated muscles, FMRP expression has been described in all investigated tissues [29], including megakaryocytes [30] and platelets [31]. FMRP is an RNA-binding protein having well-known RNA-binding motifs, one RGG-box and two KH domains [32], and is involved in transport and translation regulation of mRNAs. In fact, 95% of FMRP is normally associated with polyribosomes in mouse brain tissue [33] and in human HeLa [34] and megakaryoblastic MEG-01 [30] cells, but not in human platelets [31]. In brain neurons, FMRP specifically binds nearly 4% of all mRNAs [35] and plays a crucial role in local activity-dependent synaptic protein synthesis by acting chiefly as a translational repressor of its target mRNAs through ribosomal translocation stalling [36]. Many of these target mRNAs encode essential synaptic plasticity-related and translational control signaling pathways proteins, some of which have also been associated with increased risk of ASD (e.g., PTEN, TSC2, neurexin1) [37]. This FMRP-controlled protein synthesis is further thought to underlie learning, memory, and behavioral modulation owing to its involvement in synaptogenesis and long-term plasticity [35,38–40]. FMRP lies at the crossroads of the two major translational control signaling cascades downstream of group 1 (Gp1) metabotropic glutamate receptors (mGluR1 and mGluR5), that is the mitogen-activated protein kinase—extracellular signal-regulated kinase (MAPK/ERK) and the phosphoinositide 3-kinase—Akt—mammalian target of rapamycin (PI3K/Akt/mTOR) pathways (Figure 1A). FMRP normally works by functionally opposing the pro-translational effects of the Gp1 mGluR signaling network [41]. The synaptic stimulation of Gp1 mGluR therefore culminates in facilitation of translation, which in turn facilitates long-term depression (LTD) plasticity via post-synaptic AMPA receptors endocytosis [42,43].