scholarly journals Differential Levels of Telomeric Oxidized Bases and TERRA Transcripts in Childhood Autism

2020 ◽  
Author(s):  
Mohammad Eftekhar ◽  
Yasin Panahi ◽  
Fahimeh Salasar Moghaddam ◽  
Mohammad Reza Eskandari ◽  
Hamid Pezeshk ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Children With Autism ◽  
Childhood Autism ◽  
Sexually Dimorphic ◽  
Healthy Controls ◽  
Rna Transcripts ◽  
Repeat Content ◽  
Relative Telomere Length ◽  
Syndromic Autism ◽  
Telomeric Rna

AbstractThe underlying molecular mechanisms responsible for the etiology of autism and its sex-biased prevalence remain largely elusive. Abnormally shortened telomeres have recently been associated with autism. We have previously shown that children with non-syndromic autism exhibit a sexually dimorphic pattern of relative telomere length (RTL). Only male children with autism have significantly shorter RTLs than the healthy controls and paired siblings. Autistic females have substantially longer RTLs than autistic males. Aberrantly high levels of oxidative stress plays a fundamental role in the pathophysiology of autism, and telomeres are thought to be susceptible to oxidative damage due to their high guanine-repeat content. Employing a quantitative PCR (qPCR)-based method, telomeric oxidized base lesions were measured using genomic DNA extracted from saliva samples, and levels of telomeric RNA transcripts know as TERRA were evaluated using reverse transcriptase qPCR technique. Our data show that the autistic children exhibit substantially higher levels of oxidative base lesions at their telomeres than the healthy controls and paired siblings. Intriguingly, despite having significantly longer RTLs, female children with autism have even higher levels of telomeric oxidized bases than their male counterparts. Furthermore, despite having significantly shorter RTLs, the male children with autism exhibit lower levels of TERRA expression from the short arms of chromosomes 17 and X/P compared to their individually-matched healthy controls. These findings open a fresh angle into autism. Abnormal TL and high levels of telomeric oxidized bases may serve as biomarkers for childhood autism.

scholarly journals Sexual Dimorphism in Telomere Length in Childhood Autism

2020 ◽  
Author(s):  
Yasin Panahi ◽  
Fahimeh Salasar Moghaddam ◽  
Khadijeh Babaei ◽  
Mohammad Eftekhar ◽  
Reza Shervin Badv ◽  
...  
Keyword(s):  
Telomere Length ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Childhood Autism ◽  
Healthy Controls ◽  
Autistic Children ◽  
Telomere Biology

ABSTRACTAutism spectrum disorders (ASD) are lifelong heterogeneous set of neurodevelopmental conditions with strikingly profound male prevalence. Differences in sex biology and hormones are thought to play key roles in ASD prevalence and outcome, but the underlying molecular mechanisms responsible for ASD sex-differential risk are not well understood. Two recent studies reported a significant association between shortened telomere length (TL) and autistic children. However, the role of gender bias has been overlooked. Here, we carefully examined the status of average TL among nonsyndromic male and female children with autism, and we also took a close look at the data from earlier reports. A total of 58 children were recruited for this project, including 24 apparently nonsyndromic autistic children (14 males and 10 females), their healthy siblings (n = 10), and 24 sex-, age, and location-matched healthy controls. Relative TLs (RTL) were assessed by the monochrom multiplex quantitative polymerase chain reaction (MMQPCR) technique, using genomic DNA extracted from saliva samples. Data analysis showed that gender and age had strong impacts on average RTLs among the study groups. In a sex stratified manner, autistic male children had significantly shorter average RTL than their female counterparts. Only male children with autism showed a homogeneous pattern of shorter RTLs compared with their respective healthy controls. Our findings are indicative of a sexually dimorphic pattern of TL in childhood autism. The data presented here have important implications for the role of telomere biology in the molecular mechanisms responsible for ASD male bias prevalence and etiology.

scholarly journals Tactile cortical responses and association with tactile reactivity in young children on the autism spectrum

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Svenja Espenhahn ◽  
Kate J. Godfrey ◽  
Sakshi Kaur ◽  
Maia Ross ◽  
Niloy Nath ◽  
...  
Keyword(s):  
Early Childhood ◽  
Young Children ◽  
Evoked Potentials ◽  
Real World ◽  
Somatosensory Evoked Potentials ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Childhood Autism ◽  
Verbal Abilities ◽  
Early Childhood Autism

Abstract Background Unusual behavioral reactions to sensory stimuli are frequently reported in individuals on the autism spectrum (AS). Despite the early emergence of sensory features (< age 3) and their potential impact on development and quality of life, little is known about the neural mechanisms underlying sensory reactivity in early childhood autism. Methods Here, we used electroencephalography (EEG) to investigate tactile cortical processing in young children aged 3–6 years with autism and in neurotypical (NT) children. Scalp EEG was recorded from 33 children with autism, including those with low cognitive and/or verbal abilities, and 45 age- and sex-matched NT children during passive tactile fingertip stimulation. We compared properties of early and later somatosensory-evoked potentials (SEPs) and their adaptation with repetitive stimulation between autistic and NT children and assessed whether these neural measures are linked to “real-world” parent-reported tactile reactivity. Results As expected, we found elevated tactile reactivity in children on the autism spectrum. Our findings indicated no differences in amplitude or latency of early and mid-latency somatosensory-evoked potentials (P50, N80, P100), nor adaptation between autistic and NT children. However, latency of later processing of tactile information (N140) was shorter in young children with autism compared to NT children, suggesting faster processing speed in young autistic children. Further, correlational analyses and exploratory analyses using tactile reactivity as a grouping variable found that enhanced early neural responses were associated with greater tactile reactivity in autism. Limitations The relatively small sample size and the inclusion of a broad range of autistic children (e.g., with low cognitive and/or verbal abilities) may have limited our power to detect subtle group differences and associations. Hence, replications are needed to verify these results. Conclusions Our findings suggest that electrophysiological somatosensory cortex processing measures may be indices of “real-world” tactile reactivity in early childhood autism. Together, these findings advance our understanding of the neurophysiological mechanisms underlying tactile reactivity in early childhood autism and, in the clinical context, may have therapeutic implications.

scholarly journals Quantitation of plasma thiamine, related metabolites and plasma protein oxidative damage markers in children with autism spectrum disorder and healthy controls

2016 ◽  
Vol 50 (sup1) ◽  
pp. S85-S90 ◽  
Author(s):  
Attia Anwar ◽  
Marina Marini ◽  
Provvidenza Maria Abruzzo ◽  
Alessandra Bolotta ◽  
Alessandro Ghezzo ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Oxidative Damage ◽  
Plasma Protein ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Healthy Controls

scholarly journals Human Sex Matters: Y-linked lysine demethylase 5D drives accelerated male osteogenic differentiation

2021 ◽  
Author(s):  
Madlen Merten ◽  
Johannes F.W. Greiner ◽  
Tarek Niemann ◽  
Meike Grosse Venhaus ◽  
Daniel Kronenberg ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Female Rats ◽  
Sexually Dimorphic ◽  
Loss Of Function ◽  
Calvarial Bone ◽  
Sexual Dimorphisms ◽  
Increased Risk ◽  
Elevated Expression ◽  
Lysine Demethylase

Female sex is increasingly associated to a loss of bone mass during aging and an increased risk for fractures developing nonunion. Hormonal factors and cell-intrinsic mechanisms are suggested to drive these sexual dimorphisms, although underlying molecular mechanisms are still a matter of debate. Here, we observed a decreased capacity of calvarial bone recovery in female rats and a profound sexually dimorphic osteogenic differentiation human adult neural crest-derived stem cells (NCSCs). Next to an elevated expression of pro-osteogenic regulators, global trancriptomics revealed Lysine Demethylase 5D (KDM5D) to be highly upregulated in differentiating male NCSCs. Loss of function by siRNA or pharmacological inhibition of KDM5D significantly reduced the osteogenic differentiation capacity of male NCSCs. In summary, we demonstrate craniofacial osteogenic differentiation to be sexually dimorphic with the expression of KDM5D as a prerequisite for accelerated male osteogenic differentiation, emphasizing the analysis of sex-specific differences as a crucial parameter for treating bone defects.

scholarly journals Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Haiming Huang ◽  
Jialin Du ◽  
Bo Jin ◽  
Lu Pang ◽  
Nan Duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Progression ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Healthy Controls ◽  
Direct Products ◽  
Diagnostic Biomarkers ◽  
Diagnostic Potential ◽  
Urine Exosomes

BackgroundThe recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study was to identify tumor progression-related mRNAs and lncRNAs in urine exosomes that could be used for detection of BCa.MethodsRNA-sequencing was performed to identify tumor progression-related biomarkers in three matched superficial tumor and deep infiltrating tumor regions of muscle-invasive bladder cancer (MIBC) specimens, differently expressed mRNAs and lncRNAs were validated in TCGA dataset (n = 391) in the discovery stage. Then candidate RNAs were chosen for evaluation in urine exosomes of a training cohort (10 BCa and 10 healthy controls) and a validation cohort (80 BCa and 80 healthy controls) using RT-qPCR. The diagnostic potential of the candidates were evaluated by receiver operating characteristic (ROC) curves.ResultsRNA sequencing revealed 8 mRNAs and 32 lncRNAs that were significantly upregulated in deep infiltrating tumor region. After validation in TCGA database, 10 markedly dysregulated RNAs were selected for further investigation in urine exosomes, of which five (mRNAs: KLHDC7B, CASP14, and PRSS1; lncRNAs: MIR205HG and GAS5) were verified to be significantly dysregulated. The combination of the five RNAs had the highest AUC to disguising the BCa (0.924, 95% CI, 0.875–0.974) or early stage BCa patients (0.910, 95% CI, 0.850 to 0.971) from HCs. The expression levels of these five RNAs were correlated with tumor stage, grade, and hematuria degrees.ConclusionsThese findings highlight the potential of urine exosomal mRNAs and lncRNAs profiling in the early diagnosis and provide new insights into the molecular mechanisms involved in BCa.

scholarly journals Identification and analysis of consensus RNA motifs binding to the genome regulator CTCF

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Shuzhen Kuang ◽  
Liangjiang Wang
Keyword(s):  
Genome Organization ◽  
Molecular Mechanisms ◽  
Short Term Memory ◽  
Consensus Sequence ◽  
Ctcf Binding ◽  
Specific Sequence ◽  
3D Genome ◽  
Rna Transcripts ◽  
Memory Network ◽  
Rna Motif

Abstract CCCTC-binding factor (CTCF) is a key regulator of 3D genome organization and gene expression. Recent studies suggest that RNA transcripts, mostly long non-coding RNAs (lncRNAs), can serve as locus-specific factors to bind and recruit CTCF to the chromatin. However, it remains unclear whether specific sequence patterns are shared by the CTCF-binding RNA sites, and no RNA motif has been reported so far for CTCF binding. In this study, we have developed DeepLncCTCF, a new deep learning model based on a convolutional neural network and a bidirectional long short-term memory network, to discover the RNA recognition patterns of CTCF and identify candidate lncRNAs binding to CTCF. When evaluated on two different datasets, human U2OS dataset and mouse ESC dataset, DeepLncCTCF was shown to be able to accurately predict CTCF-binding RNA sites from nucleotide sequence. By examining the sequence features learned by DeepLncCTCF, we discovered a novel RNA motif with the consensus sequence, AGAUNGGA, for potential CTCF binding in humans. Furthermore, the applicability of DeepLncCTCF was demonstrated by identifying nearly 5000 candidate lncRNAs that might bind to CTCF in the nucleus. Our results provide useful information for understanding the molecular mechanisms of CTCF function in 3D genome organization.

scholarly journals The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice

2019 ◽  
Vol 5 (2) ◽  
pp. eaau8317 ◽  
Author(s):  
Peng Zheng ◽  
Benhua Zeng ◽  
Meiling Liu ◽  
Jianjun Chen ◽  
Junxi Pan ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Brain Function ◽  
Molecular Mechanisms ◽  
Diversity Index ◽  
Area Under The Curve ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Germ Free ◽  
Α Diversity ◽  
Neurologic Function

Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mechanisms. The gut microbiome can modulate brain function and behaviors through the microbiota-gut-brain axis. Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (HCs). Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve. Compared to HCs, germ-free mice receiving SCZ microbiome fecal transplants had lower glutamate and higher glutamine and GABA in the hippocampus and displayed SCZ-relevant behaviors similar to other mouse models of SCZ involving glutamatergic hypofunction. Together, our findings suggest that the SCZ microbiome itself can alter neurochemistry and neurologic function in ways that may be relevant to SCZ pathology.

scholarly journals Expression Profiling and Clinical Significance of Plasma MicroRNAs in Diabetic Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jianqin Wang ◽  
Gouqin Wang ◽  
Yaojun Liang ◽  
Xiaochun Zhou
Keyword(s):  
Diabetic Nephropathy ◽  
Clinical Significance ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Clinicopathological Parameters ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Plasma Samples ◽  
Expression Levels ◽  
Plasma Mirnas

Aims. MicroRNAs (miRNAs) stably and abundantly exist in body fluids and have been considered as novel and noninvasive biomarkers for several diseases. The present study is aimed at investigating the expression profiling and clinical significance of plasma miRNAs in the pathogenesis and progression of diabetic nephropathy (DN). Methods. Plasma samples were obtained from 66 DN patients (36 had microalbuminuria and 30 had macroalbuminuria), 36 diabetic patients with normoalbuminuria, and 40 healthy controls. The plasma miRNA profiles were obtained by miRNA low-density array chip and validated by quantitative real-time polymerase chain reaction. The correlations between the differential expression of plasma miRNAs and clinicopathological parameters were explored. Results. miR-150-5p, miR-155-5p, miR-30e, miR-320e, and miR-3196 were found to be differentially expressed in plasma samples among these three groups: diabetic patients with microalbuminuria, diabetic patients with normoalbuminuria, and healthy controls (P<0.05). The expression levels of miR-150-5p and miR-155-5p in patients with macroalbuminuria were 2.3-fold (P=0.001) and 1.5-fold (P=0.033) higher than patients with microalbuminuria, respectively. However, the expression levels of miR-30e, miR-3196, miR-320, and let-7a-5p were not significantly different between these two groups (P>0.05). Furthermore, plasma miR-150-5p (P=0.016, r = -0.460) and miR-155-5p (P=0.014, r = -0.467) were negatively correlated with the albuminuria excretion rate, while plasma miR-150-5p (P=0.01, r = 0.318) and miR-155-5p (P=0.030, r=0.271) were positively correlated with the estimated glomerular filtration rate. Conclusion. miR-150-5p, miR-155-5p, miR-30e, miR-320e, and miR-3196 are potentially new diagnostic biomarkers for early DN. miR-150-5p and miR-155-5p may be involved in the pathogenesis and progression of DN. Further research is required to verify these findings and clarify the specific molecular mechanisms.

scholarly journals Sex-specific differences in neonatal hyperoxic lung injury

2016 ◽  
Vol 311 (2) ◽  
pp. L481-L493 ◽  
Author(s):  
Krithika Lingappan ◽  
Weiwu Jiang ◽  
Lihua Wang ◽  
Bhagavatula Moorthy
Keyword(s):  
Lung Injury ◽  
Lung Development ◽  
Molecular Mechanisms ◽  
Neutrophil Infiltration ◽  
Sexually Dimorphic ◽  
Female Mice ◽  
Hyperoxia Exposure ◽  
Hyperoxic Lung Injury ◽  
Mean Linear Intercept ◽  
Radial Alveolar Count

Male sex is considered an independent predictor for the development of bronchopulmonary dysplasia (BPD) after adjusting for other confounders. BPD is characterized by an arrest in lung development with marked impairment of alveolar septation and vascular development. The reasons underlying sexually dimorphic outcomes in premature neonates are not known. In this investigation, we tested the hypothesis that male neonatal mice will be more susceptible to hyperoxic lung injury and will display larger arrest in lung alveolarization. Neonatal male and female mice (C57BL/6) were exposed to hyperoxia [95% FiO2, postnatal day (PND) 1–5] and euthanized on PND 7 and 21. Extent of alveolarization, pulmonary vascularization, inflammation, and modulation of the NF-κB pathway were determined and compared with room air controls. Macrophage and neutrophil infiltration was significantly increased in hyperoxia-exposed animals but was increased to a larger extent in males compared with females. Lung morphometry showed a higher mean linear intercept (MLI) and a lower radial alveolar count (RAC) and therefore greater arrest in lung development in male mice. This was accompanied by a significant decrease in the expression of markers of angiogenesis (PECAM1 and VEGFR2) in males after hyperoxia exposure compared with females. Interestingly, female mice showed increased activation of the NF-κB pathway in the lungs compared with males. These results support the hypothesis that sex plays a crucial role in hyperoxia-mediated lung injury in this model. Elucidation of the sex-specific molecular mechanisms may aid in the development of novel individualized therapies to prevent/treat BPD.

scholarly journals PO-046 Gene expression profiling of peripheral blood mononuclear cells in young male trampoline athletes

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Li Gao ◽  
Yong Jie Yang ◽  
En Qi Li ◽  
Jia Ning Mao
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Bone Health ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Healthy Controls ◽  
Mineral Density

Objective Evidence indicates that physical activity influence bone health. However, the molecular mechanisms mediating the beneficial adaptations to exercise are not well understood. The purpose of this study was to examine the differentially expressed genes in PBMC between athletes and healthy controls, and to analyze the important functional genes and signal pathways that cause increased bone mineral density in athletes, in order to further reveal the molecular mechanisms of exercise promoting bone health. Methods Five professional trampoline athletes and five age-matched untrained college students participated in this study. Used the human expression Microarray V4.0 expression profiling chip to detect differentially expressed genes in the two groups, and performed KEGG Pathway analysis and application of STRING database to construct protein interaction Network; Real-Time PCR technology was used to verify the expression of some differential genes.  Results Compared with healthy controls, there were significant improvement in lumbar spine bone mineral density, and 236 up-regulated as well as 265 down-regulated in serum samples of athletes. The differentially expressed genes involved 28 signal pathways, such as cell adhesion molecules. Protein interaction network showed that MYC was at the core node position. Real-time PCR results showed that the expression levels of CD40 and ITGα6 genes in the athletes were up-regulated compared with the healthy controls, the detection results were consistent with that of the gene chip. Conclusions The findings highlight that long-term high-intensity trampoline training could induce transcriptional changes in PBMC of the athletes. These data suggest that gene expression fingerprints can serve as a powerful research tool to design novel strategies for monitoring exercise. The findings of the study also provide support for the notion that PBMC could be used as a substitute to study exercise training that affects bone health.

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