1. Alhosaini K, Ansari MA, Nadeem A, Attia SM, Bakheet SA, Al-Ayadhi LY, Mahmood HM, Al-Mazroua HA, Ahmad SF. Dysregulation of Ki-67 Expression in T Cells of Children with Autism Spectrum Disorder. Children (Basel, Switzerland). 2021 ; 8(2).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral abnormalities such as impairments in social function and deficits in communication. The etiology of autism is unknown in most cases, but many studies have pointed towards the immune system as a causative agent in autism. Specific studies implicated lymphocytes, natural killer (NK) cells, monocytes, cytokines, and specific transcription factors in the development of ASD. The protein Ki-67 is n expressed in the proliferating cells and is used as a tool in several disorders. Ki-67 plays a crucial role in many neurological diseases. However, Ki-67 role in ASD is not fully understood. In this study, we investigated the possible role of Ki-67 expression in autistic children. We compared Ki-67 production in CD3+, CD4+, CD8+, CXCR4+, CXCR7+, CD45R+, HLA-DR+, GATA3+, Helios+, and FOXP3+ peripheral blood mononuclear cells (PBMCs) in autistic children to typically developing (TD) controls using immunofluorescence staining. We also determined Ki-67 mRNA levels in PBMCs using RT-PCR. The results revealed that autistic children had significantly increased numbers of CD3+Ki-67+, CD4+Ki-67+, CD8+Ki-67+, CXCR4+Ki-67+, CXCR7+Ki-67+, CD45R+Ki-67+, HLA-DR+Ki-67+, CXCR4+GATA3+, GATA3+Ki-67+ cells and decreased Helios+Ki-67+ and FOXP3+Ki-67+ cells compared with TD controls. In addition, the autistic children showed upregulation of Ki-67 mRNA levels compared with TD controls. Further studies need to be carried out to assess the exact role of Ki-67 and its therapeutic potential in ASD.

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2. Fielding-Gebhardt H, Bredin-Oja SL, Warren SF, Brady NC. Rethinking Measurement Standards of Autism Symptomology in Adolescents with Fragile X Syndrome. J Autism Dev Disord. 2021.

Accurate representation of autism spectrum disorder (ASD) in fragile X syndrome (FXS) is necessary for the field. We examined classifications of ASD using three approaches-Autism Diagnostic Observation Schedule (ADOS-2 ; Lord et al. 2012), Childhood Autism Rating Scale (CARS2-ST ; Schopler et al. 2010), and Vineland Adaptive Behavior Scales (VABS-II ; Sparrow et al. 2005)-in 45 adolescents with FXS. Maladaptive items from the VABS-II plus a maternal interview were matched with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5 ; American Psychiatric Association 2013) criteria for ASD. Results indicated discrepant classifications. The ADOS-2 yielded the highest rate of comorbid autism (71%) ; CARS2-ST and VABS-II/DSM-5 yielded lower rates (38% and 42%, respectively). A singular measure of autism symptomology is insufficient to characterize autism in FXS.

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3. Goel A, Aschner M. The Effect of Lead Exposure on Autism Development. International journal of molecular sciences. 2021 ; 22(4).

Autism Spectrum Disorder (ASD) remains one of the most detrimental neurodevelopmental conditions in society today. Common symptoms include diminished social and communication ability. Investigations on autism etiology remain largely ambiguous. Previous studies have highlighted exposure to lead (Pb) may play a role in ASD. In addition, lead has been shown to be one of the most prevalent metal exposures associated with neurological deficits. A semi-systematic review was conducted using public databases in order to evaluate the extent of lead’s role in the etiology of autism. This review examines the relationship between autistic comorbid symptoms-such as deterioration in intelligence scores, memory, language ability, and social interaction-and lead exposure. Specifically, the mechanisms of action of lead exposure, including changes within the cholinergic, dopaminergic, glutamatergic, gamma aminobutyric acid (GABA)ergic systems, are discussed. The goal of this review is to help illustrate the connections between lead’s mechanistic interference and the possible furthering of the comorbidities of ASD. Considerations of the current data and trends suggest a potential strong role for lead in ASD.

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4. Malsagova KA, Pleshakova TO, Popov VP, Kupriyanov IN, Galiullin RA, Kozlov AF, Shumov ID, Kaysheva AL, Tikhonenko FV, Archakov AI, Ivanov YD. Optical Monitoring of the Production Quality of Si-Nanoribbon Chips Intended for the Detection of ASD-Associated Oligonucleotides. Micromachines. 2021 ; 12(2).

Gas-phase etching and optical lithography were employed for the fabrication of a silicon nanoribbon chip (Si-NR chip). The quality of the so-fabricated silicon nanoribbons (Si-NRs) was monitored by optical Raman scattering spectroscopy. It was demonstrated that the structures of the Si-NRs were virtually defect-free, meaning they could be used for highly sensitive detection of biological macromolecules. The Si-NR chips were then used for the highly sensitive nanoelectronics detection of DNA oligonucleotides (oDNAs), which represent synthetic analogs of 106a-5p microRNA (miR-106a-5p), associated with the development of autism spectrum disorders in children. The specificity of the analysis was attained by the sensitization of the Si-NR chip sur-face by covalent immobilization of oDNA probes, whose nucleotide sequence was complementary to the known sequence of miR-106a-5p. The use of the Si-NR chip was demonstrated to al-low for the rapid label-free real-time detection of oDNA at ultra-low ( 10(-17) M) concentrations.

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5. O’Rourke E, Coderre EL. Implicit Semantic Processing of Linguistic and Non-linguistic Stimuli in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2021.

While many individuals with autism spectrum disorder (ASD) experience difficulties with language processing, non-linguistic semantic processing may be intact. We examined neural responses to an implicit semantic priming task by comparing N400 responses-an event-related potential related to semantic processing-in response to semantically related or unrelated pairs of words or pictures. Adults with ASD showed larger N400 responses than typically developing adults for pictures, but no group differences occurred for words. However, we also observed complex modulations of N400 amplitude by age and by level of autistic traits. These results offer important implications for how groups are delineated and compared in autism research.

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6. Rahbar MH, Samms-Vaughan M, Saroukhani S, Bressler J, Hessabi M, Grove ML, Shakspeare-Pellington S, Loveland KA, Beecher C, McLaughlin W. Associations of Metabolic Genes (GSTT1, GSTP1, GSTM1) and Blood Mercury Concentrations Differ in Jamaican Children with and without Autism Spectrum Disorder. Int J Environ Res Public Health. 2021 ; 18(4).

We investigated interactive roles of three metabolic glutathione S-transferase (GST) genes (GSTP1, GSTT1, and GSTM1) and autism spectrum disorder (ASD) status in relation to blood Hg concentrations (BHC) of Jamaican children. We used data from 266 children (2-8 years) with ASD and their 1:1 age- and sex-matched typically developing (TD) controls. After adjusting General Linear Models for child’s age, socioeconomic status, consumption of leafy vegetables, fried plantain, canned fish, and the interaction between GSTP1 and GSTT1, we found significant interactions between GSTP1 and ASD status in relation to BHC either in a co-dominant or dominant genetic model for GSTP1(P < 0.001, P = 0.007, respectively). In the co-dominant model for the Ile105Val GSTP1 polymorphism, geometric mean (GM) BHC in ASD cases with genotype Ile/Ile were significantly higher than in cases with the Ile/Val genotype (0.73 vs. 0.48 µg/L, P = 0.01). In contrast, in TD controls with the Ile/Val genotype GM BHC were significantly higher than in those with the Ile/Ile genotype (0.72 vs. 0.49 µg/L, P = 0.03) or the Val/Val genotype (0.72 vs. 0.51 µg/L, P = 0.04). Although our findings are consistent with the role of GSTP1 in detoxification of Hg, replication in other populations is warranted.

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7. Sundaram SM, Schwaninger M. Parvocellular Oxytocin Neurons and Autism Spectrum Disorders. Trends in endocrinology and metabolism : TEM. 2021.

The underlying mechanism of oxytocin (OT) neurons in the development of social interaction remains unclear. In a recent study, Lewis et al. characterized OT neuronal subtypes and provided evidence that expression of the autism spectrum disorder (ASD) gene Fmr1 in parvocellular OT neurons is essential for peer-peer but not filial social interactions.

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8. Janickova L, Rechberger KF, Wey L, Schwaller B. Correction to : Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo : a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes. Mol Autism. 2021 ; 12(1) : 7.

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9. Osório JMA, Rodríguez-Herreros B, Romascano D, Junod V, Habegger A, Pain A, Richetin S, Yu P, Isidor B, Van Maldergem L, Pons L, Manificat S, Chabane N, Jequier Gygax M, Maillard AM. Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD. Mol Autism. 2021 ; 12(1) : 8.

BACKGROUND : Sensory processing atypicalities are frequent in Autism Spectrum Disorder (ASD) and neurodevelopmental disorders (NDD). Different domains of sensory processing appear to be differentially altered in these disorders. In this study, we explored the sensory profile of two clinical cohorts, in comparison with a sample of typically developing children. METHODS : Behavioral responses to sensory stimuli were assessed using the Sensory Processing Measure (parent-report questionnaire). We included 121 ASD children, 17 carriers of the 16p11.2 deletion (Del 16p11.2) and 45 typically developing (TD) children. All participants were aged between 2 and 12 years. Additional measures included the Tactile Defensiveness and Discrimination Test-Revised, Wechsler Intelligence Scales and Autism Diagnostic Observation Schedule (ADOS-2). Statistical analyses included MANCOVA and regression analyses. RESULTS : ASD children score significantly higher on all SPM subscales compared to TD. Del16p11.2 also scored higher than TD on all subscales except for tactile and olfactory/taste processing, in which they score similarly to TD. When assessing sensory modulation patterns (hyper-, hypo-responsiveness and seeking), ASD did not significantly differ from del16p11.2. Both groups had significantly higher scores across all patterns than the TD group. There was no significant association between the SPM Touch subscale and the TDDT-R. LIMITATIONS : Sensory processing was assessed using a parent-report questionnaire. Even though it captures observable behavior, a questionnaire does not assess sensory processing in all its complexity. The sample size of the genetic cohort and the small subset of ASD children with TDDT-R data render some of our results exploratory. Divergence between SPM Touch and TDDT-R raises important questions about the nature of the process that is assessed. CONCLUSIONS : Touch and olfaction/taste seem to be particularly affected in ASD children compared to del16p11.2. These results indicate that parent report measures can provide a useful perspective on behavioral expression. Sensory phenotyping, when combined with neurobiological and psychophysical methods, might have the potential to provide a better understanding of the sensory processing in ASD and in other NDD.

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10. Ellis RE, Milne E, Levita L. Reduced visual cortical plasticity in autism spectrum disorder. Brain Res Bull. 2021 ; 170 : 11-21.

There is increasing evidence implicating altered NMDA-receptor function in autism spectrum disorder (ASD). To investigate potential alterations in NMDA-dependent cortical plasticity in ASD, we examined the effect of visual high-frequency stimulation (HFS) on changes in plasticity in the visual cortex, measured by persistent changes in visual evoked potentials (VEPs), in individuals with ASD (n = 16) and neurotypical controls (NT ; n = 15). VEPs were elicited by a checkerboard circle (0.83 Hz, 2-min blocks) at baseline and at 2, 4, and 20 min following exposure to HFS (8.87 Hz, 2 min), previously shown to induce LTP-like changes in the visual cortex. Difference waves were created by subtracting VEPs measured at baseline from each Post-HFS measure, and group differences assessed. We found that HFS resulted in reduced short-term potentiation of VEPs in ASD compared to NT participants. Thus, whilst ASD participants showed significant potentiation of the VEP immediately after HFS, this enhancement was not maintained, and only persisted into the second post-HFS assessment block in NT participants. Notably, ASD individuals who self-reported being more sensitive to visual stimuli showed greater shorter-term potentiation following visual HFS. Critically, there were no group differences in degree of neural entrainment to the visual HFS, or in attentional vigilance and task performance. These findings suggests that visual cortical plasticity is atypical in ASD, results consistent with reported altered NMDA receptor function in ASD.

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11. Trakoli A. Autism Equality in the Workplace. Removing Barriers and Challenging Discrimination. Occupational medicine (Oxford, England). 2021 ; 71(1) : 48.

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12. Faial T. Perturbing autism risk genes. Nat Genet. 2021 ; 53(2) : 127.

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13. Faundes V, Jennings MD, Crilly S, Legraie S, Withers SE, Cuvertino S, Davies SJ, Douglas AGL, Fry AE, Harrison V, Amiel J, Lehalle D, Newman WG, Newkirk P, Ranells J, Splitt M, Cross LA, Saunders CJ, Sullivan BR, Granadillo JL, Gordon CT, Kasher PR, Pavitt GD, Banka S. Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine. Nat Commun. 2021 ; 12(1) : 833.

The structure of proline prevents it from adopting an optimal position for rapid protein synthesis. Poly-proline-tract (PPT) associated ribosomal stalling is resolved by highly conserved eIF5A, the only protein to contain the amino acid hypusine. We show that de novo heterozygous EIF5A variants cause a disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism. Yeast growth assays, polysome profiling, total/hypusinated eIF5A levels and PPT-reporters studies reveal that the variants impair eIF5A function, reduce eIF5A-ribosome interactions and impair the synthesis of PPT-containing proteins. Supplementation with 1 mM spermidine partially corrects the yeast growth defects, improves the polysome profiles and restores expression of PPT reporters. In zebrafish, knockdown eif5a partly recapitulates the human phenotype that can be rescued with 1 µM spermidine supplementation. In summary, we uncover the role of eIF5A in human development and disease, demonstrate the mechanistic complexity of EIF5A-related disorder and raise possibilities for its treatment.

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