Based sample of Beixinjing Blocks aged 60 years or older. Its prevalence

Based sample of Beixinjing Blocks aged 60 years or older. Its prevalence was lower than in Western countries and in Chinese subjects in Handan, and it was associated with diabetes and higher level of education. Furthermore, iERM causes a substantial decrease in visual acuity.AcknowledgmentsThe authors thank the staff and participants in Beixinjing study for their valuable skill and support.Author ContributionsConceived and designed the experiments: HDZ XX XZ. Performed the experiments: HDZ JJP XFZ JF WWW. Analyzed the data: XFZ JJP HDZ. Contributed reagents/materials/analysis tools: HDZ XFZ. Wrote the paper: XFZ HDZ JJP.
The onset rate of fragile X syndrome (FXS) is approximately one in 4000 males and one in 8000 females affected [1,2]. The clinical features of FXS include attention deficits, hyperactivity, social deficits, anxiety disorder and deficits in cognitive flexibility [3]. This syndrome is most commonly caused by a triplet ML 281 site repeat expansion (CGG) mutation in the fmr1 gene that encodes FMRP, the fragile X mental retardation protein [4,5,6]. When the CGG expansions within the 59 untranslated region (UTR) of the fmr1 gene exceed 200 repeats (the full mutation), the hypermethylation [7] and deacetylation [8] of fmr1 result, leading to the silencing of fmr1 transcription and the absence of the FMR1 protein (FMRP). FMRP, a cytoplasmic mRNA-binding protein, is widely expressed in various tissues with the most abundant expression in the brain and testes of mammalians [9,10]. For example, FMRP is expressed in neurons, particularly those of the hippocampus, amygdala, and in the Purkinje cells of the cerebellum [10,11]. In addition, the functional domains of FMRP that are evolutionarily conserved between humans and Drosophila include the nuclear localization signal (NLS) and two KH domains, the nuclear export signal (NES) and an RGG box. In humans, FMRP is highly expressed in neurons of the brain, where it is suggested to play an important role in the regulation of local mRNA translation within neuronal dendritic spines and altered synaptic function [12].Animal models of FXS have greatly facilitated the investigation of the molecular and cellular mechanism of this disorder. For example, fmr1 knockout (KO) mice were characterized as having several behavioral profiles similar to those of fragile X patients, including hyperactivity, reduced anxiety-related behavior, and learning and memory deficits [13,14]. Synapse function is TA-01 closely correlated with dendritic spine morphology and synaptic activity. Indeed, abnormalities of the dendritic spine is a significant neuroanatomical defect in FXS patients [15] and fmr1 KO mice [16]. Therefore, the findings of a spine morphological phenotype indicate a possible defect in synaptic plasticity in FXS that could result in the cognitive disability phenotype. Long-term potentiation (LTP) and long-term depression (LTD) are the key cellular mechanisms underlying learning and memory processes [17,18]. Consistent with behavioral learning deficits, electrophysiological studies have reported the loss of LTP in the anterior cingulate cortex (ACC) and the lateral amygdala of fmr1 KO mice [19]. However, previous studies have also shown that a lack of FMRP may lead to exaggerated metabotropic glutamate receptor (mGluR) signaling and enhanced hippocampal LTD in fmr1 KO mice [20]. The zebrafish is a small tropical freshwater teleost native to South-East Asia. Zebrafish were first used for biological research purposes.Based sample of Beixinjing Blocks aged 60 years or older. Its prevalence was lower than in Western countries and in Chinese subjects in Handan, and it was associated with diabetes and higher level of education. Furthermore, iERM causes a substantial decrease in visual acuity.AcknowledgmentsThe authors thank the staff and participants in Beixinjing study for their valuable skill and support.Author ContributionsConceived and designed the experiments: HDZ XX XZ. Performed the experiments: HDZ JJP XFZ JF WWW. Analyzed the data: XFZ JJP HDZ. Contributed reagents/materials/analysis tools: HDZ XFZ. Wrote the paper: XFZ HDZ JJP.
The onset rate of fragile X syndrome (FXS) is approximately one in 4000 males and one in 8000 females affected [1,2]. The clinical features of FXS include attention deficits, hyperactivity, social deficits, anxiety disorder and deficits in cognitive flexibility [3]. This syndrome is most commonly caused by a triplet repeat expansion (CGG) mutation in the fmr1 gene that encodes FMRP, the fragile X mental retardation protein [4,5,6]. When the CGG expansions within the 59 untranslated region (UTR) of the fmr1 gene exceed 200 repeats (the full mutation), the hypermethylation [7] and deacetylation [8] of fmr1 result, leading to the silencing of fmr1 transcription and the absence of the FMR1 protein (FMRP). FMRP, a cytoplasmic mRNA-binding protein, is widely expressed in various tissues with the most abundant expression in the brain and testes of mammalians [9,10]. For example, FMRP is expressed in neurons, particularly those of the hippocampus, amygdala, and in the Purkinje cells of the cerebellum [10,11]. In addition, the functional domains of FMRP that are evolutionarily conserved between humans and Drosophila include the nuclear localization signal (NLS) and two KH domains, the nuclear export signal (NES) and an RGG box. In humans, FMRP is highly expressed in neurons of the brain, where it is suggested to play an important role in the regulation of local mRNA translation within neuronal dendritic spines and altered synaptic function [12].Animal models of FXS have greatly facilitated the investigation of the molecular and cellular mechanism of this disorder. For example, fmr1 knockout (KO) mice were characterized as having several behavioral profiles similar to those of fragile X patients, including hyperactivity, reduced anxiety-related behavior, and learning and memory deficits [13,14]. Synapse function is closely correlated with dendritic spine morphology and synaptic activity. Indeed, abnormalities of the dendritic spine is a significant neuroanatomical defect in FXS patients [15] and fmr1 KO mice [16]. Therefore, the findings of a spine morphological phenotype indicate a possible defect in synaptic plasticity in FXS that could result in the cognitive disability phenotype. Long-term potentiation (LTP) and long-term depression (LTD) are the key cellular mechanisms underlying learning and memory processes [17,18]. Consistent with behavioral learning deficits, electrophysiological studies have reported the loss of LTP in the anterior cingulate cortex (ACC) and the lateral amygdala of fmr1 KO mice [19]. However, previous studies have also shown that a lack of FMRP may lead to exaggerated metabotropic glutamate receptor (mGluR) signaling and enhanced hippocampal LTD in fmr1 KO mice [20]. The zebrafish is a small tropical freshwater teleost native to South-East Asia. Zebrafish were first used for biological research purposes.