China 
Africa 
Explore chapters and articles related to this topic
Death Receptor-Mediated Apoptosis and Lymphocyte Homeostasis
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Lixin Zheng, Richard M. Siegel, Jagan R. Muppidi, Felicita Hornung, Michael J. Lenardo
There are other molecules that have been suggested to have roles in thymic selection. Nur77 and Nor-1, are homologous orphan nuclear steroid receptors that have been shown to promote negative selection in a redundant fashion.50,51 The retinoic acid-related orphan receptor (RORy) seems to provide survival signals during thymic selection.52 Additional molecules like thymocyte glucocorticoid receptors (GR),53 cyclin-dependent kinase 2 (Cdk2),54 and helix-loop-helix proteins like enhancer binding (E) proteins and inhibitor of DNA binding (Id) proteins55,56 are also believed to play roles in thymic selection and thymocyte differentiation. How all these molecules act in concert has yet to be determined.
Circadian System and Diurnal Activity
Published in Anthony N. Nicholson, The Neurosciences and the Practice of Aviation Medicine, 2017
These findings can be explained, at least in part, by the action of a nuclear orphan receptor Rev-Erbα (Reppert and Weaver, 2002). As well as driving the expression of PERs and CRYs, CLOCK:BMAL1 also enhances expression of Rev-Erbα via an E-box, and thus REV-ERBα protein synthesis. REV-ERBα then feeds back to inhibit Bmal1 transcription by acting through ROR response elements in the Bmal1 promoter (Preitner et al., 2002; Ueda et al., 2002). The inhibition produced by REV-ERBα is removed by the CRY negative feedback loop on the CLOCK:BMAL1 heterodimer, which leads to a disinhibition (activation) of Bmal1. The central drive of the clock may in turn be modulated by DEC1 and DEC2, as these proteins are capable of inhibiting CLOCK:BMAL1-mediated transcriptional activation in vitro, through either direct protein–protein interactions or competition for E-box binding (Honma, et al., 2002). Light detection by the eye triggers a cascade of events that ultimately increases the expression levels of Per1–2 (Albrecht et al., 1997; Shearman et al., 1997; Shigeyoshi et al., 1997; Takumi et al., 1998; Zylka et al., 1998) and Dec1 (Honma et al., 2002). Altered levels of these genes and their protein products acts to advance or delay the molecular feedback loops and so aligns the molecular clock to the light–dark cycle.
Modeling Neuroretinal Development and Disease in Stem Cells
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Photoreceptor development is controlled by several different types of transcription factors. The homeodomain transcription factor orthodenticle homeobox 2 (Otx2) is an early factor that biases progenitor cells to become photoreceptors: conditional deletion of Otx2 leads to loss of photoreceptors; retroviral gene transfer of Otx2 into retinal progenitors promotes the photoreceptor fate (Nishida et al., 2003). Otx2 also activates the transcription of CRX (Furukawa et al., 1997), which is also required for the expression of photoreceptor-specific genes, including the opsins. In mice lacking Crx, photoreceptor cells do differentiate but completely fail to mature and eventually undergo apoptosis. Blimp1, a third critical and newly identified factor (Brzezinski et al., 2010) in mice, is shown to critically bias photoreceptor fate over bipolar cell fate during development. In mice with conditional Blimp1 deletion, there is a reduction in photoreceptor formation with a corresponding increase in differentiation of bipolar cells in the inner retina. Blimp1 has been shown to specifically repress VSX2 expression, which is required for the bipolar cell fate by binding to the enhancer region of VSX2 and blocking its activity (Katoh et al., 2010). A cis-regulatory element, B108, has recently been described as critical for Blimp1 expression and function (Wang et al., 2014). Otx2 and retinoic acid-related orphan receptor β (RORβ) regulate Blimp1 expression via B108. Additionally, the studies show that Blimp1 and Otx2 formed a negative feedback loop that regulates the level of Otx2, which in turn regulates the production of the correct ratio of rods and bipolar cells.
GPR61 methylation in cord blood: a potential target of prenatal exposure to air pollutants
Published in International Journal of Environmental Health Research, 2022
Feifei Feng, Li Huang, Guoyu Zhou, Jia Wang, Ruiqin Zhang, Zhiyuan Li, Yawei Zhang, Yue Ba
In this study, we identified a total of 207 genes with significantly correlated methylation levels in 12 mother-infant pairs using genome-wide methylation approach, and found a higher methylation level of the GPR61 gene both in mothers and newborns. GPR61 is an orphan receptor that is predominantly expressed in the brain, although its ligand and functions have not yet been identified (Lee et al. 2001; Toyooka et al. 2009). It has been reported that GPR61 deficiency causes hyperphagia and obesity in GPR61-deficient mice, which suggests that it may be involved in various physiological functions including food intake and body weight (Nambu et al. 2011). Moreover, studies have shown that GPR61 may be associated with soft-tissue tumors (Hur et al. 2010; Azizan et al. 2012). We further validated the GPR61 methylation status in 568 mother-infant pairs and also found a moderate and positive mother-infant DNA methylation correlation in the promoter region of GPR61. This result not only shows maternal methylation patterns could influence infant GPR61 methylation pattern, but also suggests maternal health should be pay public attention to, especially during pregnancy. In addition to the known genetic variation, the effects of environmental exposures or the interactions may also be the reasons for the origin of some diseases, including type 2 diabetes (T2D) and obesity (Drong et al. 2012). Environmental exposure during pregnancy plays a vital role in adverse birth outcomes, as well as certain diseases later in life, which involves in epigenetic alterations (Wilhelm-Benartzi et al. 2012; Green and Marsit 2015; Saenen et al. 2019). Thus, it is necessary to illuminate the effects of environmental exposure during pregnancy on epigenetic alterations.