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Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a monogenic cause of autism spectrum disorders. Deficiencies in the fragile X messenger ribonucleoprotein, encoded by the FMR1 gene, lead to various anatomical and pathophysiological abnormalities and behavioral deficits, such as spine dysmorphogenesis and learning and memory impairments. Synaptic cell adhesion molecules (CAMs) play crucial roles in synapse formation and neural signal transmission by promoting the formation of new synaptic contacts, accurately organizing presynaptic and postsynaptic protein complexes, and ensuring the accuracy of signal transmission. Recent studies have implicated synaptic CAMs such as the immunoglobulin superfamily, N-cadherin, leucine-rich repeat proteins, and neuroligin-1 in the pathogenesis of FXS and found that they contribute to defects in dendritic spines and synaptic plasticity in FXS animal models. This review systematically summarizes the biological associations between nine representative synaptic CAMs and FMRP, as well as the functional consequences of the interaction, to provide new insights into the mechanisms of abnormal synaptic development in FXS.
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An oxadiazole derivative(OXD) containing symmetrical pyridine-2-formamidophenyl-binded moiety was synthesised as fluorescence turn-on sensor OA1. Its ultraviolet-visible(UV-vis) and fluorescent spectra(FS) gave prominent fluorescence enhancement only for monovalent silver ion(Ag(+)) in HEPES buffer solution (10 mM, pH = 7.0, DMF-H2O, 9:1, v/v), which indicated the photo-induced electron transfer(PET) occurred from the donor of pyridine-2-formamidophenyl group to oxadiazole fluorophore. The present study demonstrated that OA1 was a viable candidate as fluorescent receptor for a new Ag(+) sensor. And the results of fluorescent spectral titration showed this sensor formed 1:1 complex with Ag(+).
Assuntos
Técnicas de Química Analítica/instrumentação , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Oxidiazóis/química , Oxidiazóis/síntese química , Piridinas/química , Prata/análise , Técnicas de Química Sintética , Fenômenos Ópticos , Prata/química , Espectrometria de FluorescênciaRESUMO
In the title hydrate, C19H15N3O3·H2O, the three aromatic groups in the quinoline derivative are close to coplanar: the central oxa-diazole fragment makes dihedral angles of 15.7â (2)° with the benzene ring and 5.30â (14)° with the quinoline ring system. In the crystal, the organic mol-ecules are connected with water mol-ecules by pairs of O-Hâ¯N hydrogen bonds involving the quinoline and oxa-diazole N atoms. The mol-ecules form stacks along the a axis, neighboring mol-ecules within each stack being related by inversion and the shortest distance between the centroids of the oxa-diazole and pyridine rings being 3.500â (2)â Å. Mol-ecules from neighboring stacks are linked by weak C-Hâ¯O hydrogen bonds, forming a three-dimensional structure.
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In the title compound, C18H13N3O2·H2O, the oxa-diazole ring forms dihedral angles 7.21â (10) and 21.25â (11)° with the quinoline and benzene rings, respectively. The crystal structure features O-Hâ¯N hydrogen bonds and is further consolidated by C-Hâ¯O hydrogen-bonding inter-actions involving the water molecule of hydration.
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Fragile X syndrome (FXS) is a common inherited cause of intellectual disabilities and single-gene cause of autism spectrum disorder (ASD), resulting from the loss of functional fragile X messenger ribonucleoprotein (FMRP), an RNA-binding protein (RBP) encoded by the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Ribonucleic acid (RNA) methylation can lead to developmental diseases, including FXS, through various mechanisms mediated by 5-hydroxymethylcytosine, 5-methylcytosine, N6-methyladenosine, etc. Emerging evidence suggests that modifications of some RNA species have been linked to FXS. However, the underlying pathological mechanism has yet to be elucidated. In this review, we reviewed the implication of RNA modification in FXS and summarized its specific characteristics for facilitating the identification of new therapeutic targets.
Assuntos
Transtorno do Espectro Autista , Síndrome do Cromossomo X Frágil , Humanos , Síndrome do Cromossomo X Frágil/genética , Transtorno do Espectro Autista/genética , RNA/metabolismo , Metilação , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismoRESUMO
In the crystal structure of the title compound, C(8)H(5)NO(4), essentially planar mol-ecules [largest deviation from the least-squares plane = 0.030â (2)â Å] form stacks along the a-axis direction. Intercentroid separations between overlapping benzene rings within the stack are 3.6594â (12)â Å and 3.8131â (12)â Å. Mol-ecules from neighboring stacks are linked by weak C-Hâ¯O hydrogen bonds into inversion dimers.
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Fragile X syndrome (FXS) is a leading form of inherited intellectual disability and single-gene cause of autism spectrum disorder (ASD) and is characterized by core deficits in cognitive flexibility, sensory sensitivity, emotion, and social interactions. Motor deficits are a shared feature of FXS and autism. The cerebellum has emerged as one of the target brain areas affected by neurodevelopmental diseases. Alterations in the cerebellar structure, circuits, and function may be the key drivers of impaired fine and gross motor skills in FXS and fragile X-associated tremor/ataxia syndrome (FXTAS). In this review, we briefly examined recent findings in FXS and present a discussion on the literature supporting motor skill deficits in FXS. Subsequently, we focused on neuropathological alterations in the cerebellum in FXS and FXTAS. We highlight studies that have directly examined the function of fragile X mental retardation protein and related epigenetic variations in the cerebellum. Overall, we obtained considerable supporting evidence for the hypothesis that cerebellar dysfunction is evident in FXS and FXTAS; however, compared with studies on other ASD models, studies on motor skills related to fragile X disorders are particularly rare and inconclusive. Hence, future research should address FXS-related motor and behavioral trajectories and examine the underlying mechanisms at both the cell and circuit levels.
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Transtorno do Espectro Autista , Síndrome do Cromossomo X Frágil , Humanos , Destreza Motora , Proteína do X Frágil da Deficiência Intelectual , Cerebelo/metabolismoRESUMO
Ribonucleic acid (RNA) methylation is the most abundant modification in biological systems, accounting for 60% of all RNA modifications, and affects multiple aspects of RNA (including mRNAs, tRNAs, rRNAs, microRNAs, and long non-coding RNAs). Dysregulation of RNA methylation causes many developmental diseases through various mechanisms mediated by N 6-methyladenosine (m6A), 5-methylcytosine (m5C), N 1-methyladenosine (m1A), 5-hydroxymethylcytosine (hm5C), and pseudouridine (Ψ). The emerging tools of RNA methylation can be used as diagnostic, preventive, and therapeutic markers. Here, we review the accumulated discoveries to date regarding the biological function and dynamic regulation of RNA methylation/modification, as well as the most popularly used techniques applied for profiling RNA epitranscriptome, to provide new ideas for growth and development.
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Corporate green innovation has played a crucial role in balancing profitability and environmental protection. The existing research on determinant factors of green innovation has its main defects in emphasizing excessively enterprise's formal institutional environment and neglecting the informal institutional environment, causing an incomplete understanding of the relationship between institutional environments and corporate green innovation. To bridge this gap, using a sample of Shanghai and Shenzhen A-share listed firms in manufacturing industry during the period of 2010-2016, we investigate how social trust, an important informal institutions, affects corporate green innovation. Our results show that social trust is positively associated with green innovation, remaining valid after applying endogenous and robustness tests. In addition, the positive relationship between social trust and green innovation is more prominent when the enterprise is non-state-owned or locates in a looser command-and-control (CAC) environmental regulations region. Further analysis shows that social trust boosts corporate green innovation via promoting knowledge sharing, decreasing financing constraints, and fulfilling more corporate social responsibility (CSR). This paper enriches the literature concerning social trust and green innovation and draws back more public attention on the role of informal institutions play in promoting green innovation.
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Organizações , Confiança , China , Conservação dos Recursos Naturais , Responsabilidade SocialRESUMO
Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region-specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway and the ventral tegmental area-nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.