Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative ...Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism.
Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n = 871) or suspected (n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n = 1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain.
The ASD (p = 6.1e-13), sibling (p = 4.9e-3) and unrelated (p = 3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r = 0.24, p = 2.1e-3) and parents (r = 0.17, p = 8.0e-7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r = 0.13, p = 1.9e-3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants.
This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered.
We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair).
Nausea and vomiting during pregnancy (NVP) is thought to be caused by changes in maternal hormones during pregnancy. Differences in hormone exposure during prenatal life have been implicated in the ...causal pathways for some cases of autism spectrum disorder (ASD). However, no study has investigated whether the presence and severity of NVP may be related to symptom severity in offspring with ASD.
A large sample of children with ASD (227 males and 60 females, aged 2 to 18 years) received a clinical assessment, during which parents completed questionnaires regarding their child's social (Social Responsiveness Scale, SRS) and communication (Children's Communication Checklist-2nd edition, CCC-2) symptoms. Parents also reported on a 5-point scale the frequency and severity of NVPs during the pregnancy of the child being assessed: (1) no NVP during the pregnancy, (2) occasional nausea, but no vomiting, (3) daily nausea, but no vomiting, (4) occasional vomiting, with or without nausea, and (5) daily nausea and vomiting.
Impairments in social responsiveness in offspring, as indexed by SRS total score, significantly increased as a function of the frequency and severity of their mothers' NVP, as did the level of language difficulties as indexed by the Global Communication Composite of the CCC-2.
The strong, positive association between increasing frequency and severity of NVP and ASD severity in offspring provides further evidence that exposure to an atypical hormonal environment during prenatal life may affect neurodevelopment and contribute to the ASD phenotype. Given that the measure of NVP symptoms in the current study was based on retrospective recall, replication of this finding is required before strong conclusions can be drawn.
There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to ...address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.
Display omitted
•Limited autism-microbiome associations from stool metagenomics of n = 247 children•Romboutsia timonensis was the only taxa associated with autism diagnosis•Autistic traits such as restricted interests are associated with less-diverse diet•Less-diverse diet, in turn, is associated with lower microbiome alpha-diversity
Large autism stool metagenomics study finds limited direct autism associations, in contrast to strong relationships with dietary traits, stool consistency, and age, suggestive of a model whereby genetic and phenotypic measures of the autism spectrum promote a less-diverse diet that reduces microbiome diversity.
Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex ...interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.
MicroRNAs (miRNAs) are emerging as a significant modulator of immunity, and their abnormal expression/activity has been linked to numerous human disorders, such as cancer. It is now known that miRNAs ...potentially modulate the production of several metabolic processes in tumor-associated immune cells and indirectly
different metabolic enzymes that affect tumor-associated signaling cascades. For instance, Let-7 has been identified as a crucial modulator for the long-lasting survival of CD8
T cells (naive phenotypes) in cancer by altering their metabolism. Furthermore, in T cells, it has been found that enhancer of zeste homolog 2 (EZH2) expression is controlled
glycolytic metabolism through miRNAs in patients with ovarian cancer. On the other hand, immunometabolism has shown us that cellular metabolic reactions and processes not only generate ATP and biosynthetic intermediates but also modulate the immune system and inflammatory processes. Based on recent studies, new and encouraging approaches to cancer involving the modification of miRNAs in immune cell metabolism are currently being investigated, providing insight into promising targets for therapeutic strategies based on the pivotal role of immunometabolism in cancer. Throughout this overview, we explore and describe the significance of miRNAs in cancer and immune cell metabolism.
•Cancer immunotherapy, has revolutionized the treatment of many malignancies.•Nanovaccines could solve diverse problems that arose during cancer immunotherapy.•Targeting DCs by nanovaccine augments ...their effectiveness with promising outcomes.
Cancer immunotherapy is proposed to eradicate tumors by stimulating host anti-tumor immunity through utilizing various therapeutic approaches. Cancer vaccines have become a promising approach for cancer immunotherapy among the proposed platforms, either alone or in combination with other therapeutic agents. Due to the suboptimal efficacy of cancer vaccines in clinical trials and the advent of nanotechnology in the biomedicine field, scientists developed nanoplatforms, such as various nanoparticles (NPs), cell-derived components, and nanocomplexes, to deliver vaccine components to target cells and tissues, thereby supporting their anti-tumor efficacy and minimizing adverse side effects. To increase the therapeutic effects of nanovaccines in cancer therapy, dendritic cell (DC) targeting through the modulation of the structure of the vaccines, such as using DC-specific ligands, has attracted extensive interest. Here, we reviewed the various forms of nanovaccines in cancer therapy and their therapeutic effects; we highlighted the properties and functions of DCs as the main antigen-presenting cells in immune responses and focused on targeting DCs in developing nanovaccines.
Acute kidney injury (AKI) is a known predictor of unfavorable outcome in patients treated at the ICU, irrespective of the disease. However, data on the potential influence of serum creatinine (sCr) ...on hospital admission on the outcome in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) is scarce. A total of 369 consecutive patients suffering from SAH were included in this retrospective cohort study. Patients were divided into good-grade (WFNS I−III) versus poor-grade (WFNS IV−V). Outcome was assessed according to the modified Rankin Scale (mRS) after 6 months and stratified into favorable (mRS 0−2) versus unfavorable (mRS 3−6). SAH patients with sCr levels <1.0 mg/dL achieved significantly a favorable outcome more often compared to patients with sCr levels ≥1.0 mg/dL (p = 0.003). In the multivariable analysis, higher levels of sCr (p = 0.014, OR 2.4; 95% CI 1.2−4.7), poor-grade on admission (p < 0.001, OR 9.8; 95% CI 5.6−17.2), age over 65 years (p < 0.001, OR 3.3; 95% CI 1.7−6.1), and delayed cerebral ischemia (p < 0.001, OR 7.9; 95% CI 3.7−17.1) were independently associated with an unfavorable outcome. We identified increased sCr on admission as a predictor for unfavorable functional outcome after SAH. Further studies elucidating the pathophysiology of this association are necessary.
Display omitted
•Recent advances and limitations in Poly(amino acids) based bio(sensing) were discussed.•The analytical figures of merit of the developed methods are also evaluated.•Current ...improvements on the monitoring of food contamination using poly(amino acids) based bio(sensors) were investigated.
Nowadays, our societies are entangled with numerous problems more and more. One of them is food safety, which has a direct relationship with public health. Indeed, food contaminations have been categorized as some important groups including bacteria, viruses, heavy metals, toxins, pesticides, food colorants and so forth. Over the last two decades, several researchers have attempted to develop sensing approaches for these contaminations. On the other hand, conventional techniques suffer from expansivity, sensitivity and selectivity. Therefore, the advancement of technology introduces a novel analytical method called bio(sensors) which provides a multi-domain sensing platform. Elaborately, the presence of different nanomaterials such as carbon-based, silica-based and metallic-based nanomaterials has revolutionized in terms of improving the properties of these analytical approaches. More importantly, poly(amino acids) as biocomposites have attracted considerable attention over the last few years. In addition, the integration of these biocomposites with nanomaterials brings about a brilliant probe for the detection of food contaminations. In this regard, in this review, we summarized recent advances in bio(sensors) based on poly(amino acids) for quantification of various food contaminations, and alongside that, the pros and cons of electrochemical and optical bio(sensor) as two major types of these analytical methods discussed.
PDF
