Action viewing and language in adolescents with autism spectrum disorder.

The mirror neuron system consists of fronto-parietal regions and responds to both goal-directed action execution and observation. The broader action observation network is specifically involved in observation of actions and is thought to play a role in understanding the goals of the motor act, the intention of others, empathy, and language. Many, but not all, studies have found mirror neuron system or action observation network dysfunction in autism spectrum disorder. The objective of this study was to use observation of a goal-directed action fMRI paradigm to examine the action observation network in autism spectrum disorder and to determine whether fronto-parietal activation is associated with language ability. Adolescents with autism spectrum disorder (n = 23) were compared to typically developing adolescents (n = 20), 11-17 years. Overall, there were no group differences in activation, however, the autism spectrum group with impaired expressive language (n = 13) had significantly reduced inferior frontal and inferior parietal activation during action viewing. In controls, right supramarginal gyrus activation was associated with higher expressive language; bilateral supramarginal and left pars opercularis activation was associated with better verbal-gesture integration. Results suggest that action-observation network dysfunction may characterize a subgroup of individuals with autism spectrum disorder with expressive language deficits. Therefore, interventions that target this dysfunctional network may improve expressive language in this autism spectrum subgroup. Future treatment studies should individualize therapeutic approaches based on brain-behavior relationships.

Preliminary Validation and Feasibility of the Autism Detection in Early Childhood-Virtual (ADEC-V) for Autism Telehealth Evaluations in a Hospital Setting.

This study provided preliminary validation of the Autism Detection in Early Childhood-Virtual (ADEC-V) for telehealth assessment of possible autism. Participants were 121 children (24.79% female) aged 18-47 months who completed telehealth evaluations at a large pediatric hospital in the Midwestern United States between October 2020 and February 2021. The ADEC-V showed good sensitivity (0.82) and specificity (0.78) and was significantly correlated with other ASD symptom measures (i.e., CARS-2, ADI-R). Internal consistency was acceptable (α = 0.77). These results need replication in a larger and broader sample including more children without ASD. This preliminary validation study identifies the ADEC-V as a promising measure for telehealth ASD assessments in young children.

Differences in Developmental Concerns of Young Children with Autism Spectrum Disorder Across Racial/Ethnic Groups.

PURPOSE: Parents/caregivers of children with autism spectrum disorder (ASD) have varying types of initial concerns regarding their child's development, which may be culturally bound to parents' perceptions of their child's development. This study investigated differences in the types of initial developmental concerns reported by parents or caregivers of different racial/ethnic groups with children in an early intervention program. METHOD: This study examined the frequency of endorsement of different types of concerns in African American, Caucasian, and Hispanic families. RESULTS: No significant differences between racial/ethnic groups were found in the endorsement of concerns related to communication, language/speech, motor, problem behavior, sensory, feeding, prematurity, attention, adaptive functioning, and medical conditions. Racial/ethnic groups differed significantly in their endorsement for social concerns. CONCLUSION: Racial/ethnic group differences were confirmed regarding initial developmental concerns related to social behavior, which may be due to cultural beliefs. The implications of these findings on early identification are discussed.

An investigation of the association between seizures, autism symptomology, and developmental functioning in young children.

OBJECTIVE: The aim of the present study was to explore whether a history of seizures was associated with autism symptom severity and developmental functioning in young children. METHODS: Autism symptom severity and developmental functioning were compared between children with and without a history or seizures who either had atypical development or met criteria for autism spectrum disorder (ASD) based on review of records by a licensed clinical psychologist. RESULTS: Parents of children who met criteria for ASD reported lower levels of autism symptomology when the child had a history of seizures, while the opposite trend was found for children with atypical development. Participants without ASD or seizures had greater developmental functioning than the other groups. CONCLUSION: The present study emphasizes the need for early identification and diagnosis of both ASD and seizure disorders, as timely intervention for these two conditions may be related to improved outcomes for young children.

A Program Evaluation of Home and Center-Based Treatment for Autism Spectrum Disorder.

The present study aimed to retrospectively compare the relative rates of mastery of exemplars for individuals with ASD (N = 313) who received home-based and center-based services. A between-group analysis found that participants mastered significantly more exemplars per hour when receiving center-based services than home-based services. Likewise, a paired-sample analysis found that participants who received both home and center-based services had mastered 100 % more per hour while at the center than at home. These analyses indicated that participants demonstrated higher rates of learning during treatment that was provided in a center setting than in the participant's home.

An evaluation of the clinical application of the DSM-5 for the diagnosis of autism spectrum disorder.

INTRODUCTION: The changes to the diagnostic criteria for autism spectrum disorder (ASD) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) were met with much controversy by researchers, clinicians, and families of individuals with ASD. The goal of this paper is to review the literature on the impact of these changes. Areas covered: This paper reviews the major changes to diagnostic criteria from DSM-IV-TR to DSM-5. It emphasizes how these changes are hypothesized to impact prevalence rates, as well as trends in characteristics of individuals who would have met previous criteria for ASD but no longer qualify for a diagnosis under DSM-5. Policy issues such as access to services and research considerations are also briefly reviewed. Expert commentary: Researchers have found that the DSM-5 diagnostic criteria for ASD may significantly impact which children receive diagnoses, which in turn affects access to services that address impairments characteristic of this disorder. Despite the fact that the DSM-5 has now been in use for four years, fewer recent studies were identified than was expected. Future research should continue to focus on the impact of changes in criteria, as well as on translational scientific advances across disciplines.

Atypical activation of action-semantic network in adolescents with autism spectrum disorder.

In typical adults, fMRI studies have shown activation of primary and pre-motor regions during action word processing. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments. ASD studies have shown atypical semantic processing and motor deficits. The objective of this study was to examine semantic processing of verbs in ASD. 15 ASD adolescents and 19 typically developing adolescents, 11-16years, completed a semantic similarity judgment task during fMRI. There were no differences in task accuracy or reaction time. At the group level, both groups had activation in left language areas; controls, but not ASD, also had activation in the left pre-supplementary motor area (pre-SMA). In ASD, less left frontal activation and reduced left lateralization of activation within these regions was associated with shorter reaction times and better language skills. More left temporal activation was associated with better language abilities in ASD. Differences in pre-SMA activation may relate to motor planning deficits or differences in approach to the semantic task in ASD. Results suggest that left frontal language areas may be less efficient in ASD and those who can compensate by recruiting more right hemisphere homologues may result in better language abilities.

Factors related to parental age of first concern in toddlers with autism spectrum disorder.

PURPOSE: The age of first concern (AOC) of parents of children with autism spectrum disorders (ASD) has substantial implications for early diagnosis and intervention. The current study sought to determine the average AOC, what types of first concerns are most common, and what factors predict earlier AOC in toddlers with ASD. METHODS: This study analyzed the predictive influence of the type of concern, symptom severity, medical diagnoses, and other independent variables on AOC among toddlers with ASD using multiple regressions. RESULTS: The mean AOC was found to be 13.97 months (SD = 7.86). The most commonly reported first concern was speech/language. First concerns related to communication, speech/language predicted later AOC, while motor concerns predicted earlier AOC. CONCLUSIONS: Concerns that are more closely related to social communication deficits characteristic of ASD predicted later AOC. The implications of these findings on screening/assessment and intervention are discussed.

Functional analysis of Agaricus bisporus serine proteinase 1 reveals roles in utilization of humic rich substrates and adaptation to the leaf-litter ecological niche.

Agaricus bisporus is a secondary decomposer fungus and an excellent model for the adaptation, persistence and growth of fungi in humic-rich environments such as soils of temperate woodland and pastures. The A. bisporus serine proteinase SPR1 is induced by humic acids and is highly expressed during growth on compost. Three Spr1 gene silencing cassettes were constructed around sense, antisense and non-translatable-stop strategies (pGRsensehph, pGRantihph and pGRstophph). Transformation of A. bisporus with these cassettes generated cultures showing a reduction in extracellular proteinase activity as demonstrated by the reduction, or abolition, of a clearing zone on plate-based bioassays. These lines were then assessed by detailed enzyme assay, RT-qPCR and fruiting. Serine proteinase activity in liquid cultures was reduced in 83% of transformants. RT-qPCR showed reduced Spr1 mRNA levels in all transformants analysed, and these correlated with reduced enzyme activity. When fruiting was induced, highly-silenced transformant AS5 failed to colonize the compost, whilst for those that did colonize the compost, 60% gave a reduction in mushroom yield. Transcriptional, biochemical and developmental observations, demonstrate that SPR1 has an important role in nutrient acquisition in compost and that SPR1 is a key enzyme in the adaptation of Agaricus to the humic-rich ecological niche formed during biomass degradation.

Global gene expression in Coprinopsis cinerea meiotic mutants reflects checkpoint arrest.

The basidiomycete Coprinopsis cinerea is well-suited to studies of meiosis because meiosis progresses synchronously in 10 million cells within each mushroom cap. Approximately 20% of C. cinerea genes exhibit changing expression during meiosis, but meiosis and mushroom development happen concurrently and therefore differentially expressed genes might not be directly involved in meiotic processes. By using microarrays, we examined global gene expression across a meiotic time course in two mutants in which meiosis arrests but mushrooms develop normally. Genes differentially expressed in the mutants compared with the wild type are likely to be involved in meiosis and sporulation as opposed to mushroom development. In rad50-1, which arrests in late prophase, RNA abundance for a group of early meiotic genes remains high, whereas the expression of a group of late meiotic genes is never induced. In contrast, in msh5-22 (which fails to undergo premeiotic DNA replication), both early and late meiotic genes are underexpressed relative to wild type at late meiotic time points as the cells die. Genes that are differentially expressed relative to wild type in both mutants are particularly strong candidates for playing roles in meiosis and sporulation.

Analysis of the Basidiomycete Coprinopsis cinerea reveals conservation of the core meiotic expression program over half a billion years of evolution.

Coprinopsis cinerea (also known as Coprinus cinereus) is a multicellular basidiomycete mushroom particularly suited to the study of meiosis due to its synchronous meiotic development and prolonged prophase. We examined the 15-hour meiotic transcriptional program of C. cinerea, encompassing time points prior to haploid nuclear fusion though tetrad formation, using a 70-mer oligonucleotide microarray. As with other organisms, a large proportion (∼20%) of genes are differentially regulated during this developmental process, with successive waves of transcription apparent in nine transcriptional clusters, including one enriched for meiotic functions. C. cinerea and the fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe diverged ∼500-900 million years ago, permitting a comparison of transcriptional programs across a broad evolutionary time scale. Previous studies of S. cerevisiae and S. pombe compared genes that were induced upon entry into meiosis; inclusion of C. cinerea data indicates that meiotic genes are more conserved in their patterns of induction across species than genes not known to be meiotic. In addition, we found that meiotic genes are significantly more conserved in their transcript profiles than genes not known to be meiotic, which indicates a remarkable conservation of the meiotic process across evolutionarily distant organisms. Overall, meiotic function genes are more conserved in both induction and transcript profile than genes not known to be meiotic. However, of 50 meiotic function genes that were co-induced in all three species, 41 transcript profiles were well-correlated in at least two of the three species, but only a single gene (rad50) exhibited coordinated induction and well-correlated transcript profiles in all three species, indicating that co-induction does not necessarily predict correlated expression or vice versa. Differences may reflect differences in meiotic mechanisms or new roles for paralogs. Similarities in induction, transcript profiles, or both, should contribute to gene discovery for orthologs without currently characterized meiotic roles.

Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus).

The mushroom Coprinopsis cinerea is a classic experimental model for multicellular development in fungi because it grows on defined media, completes its life cycle in 2 weeks, produces some 10(8) synchronized meiocytes, and can be manipulated at all stages in development by mutation and transformation. The 37-megabase genome of C. cinerea was sequenced and assembled into 13 chromosomes. Meiotic recombination rates vary greatly along the chromosomes, and retrotransposons are absent in large regions of the genome with low levels of meiotic recombination. Single-copy genes with identifiable orthologs in other basidiomycetes are predominant in low-recombination regions of the chromosome. In contrast, paralogous multicopy genes are found in the highly recombining regions, including a large family of protein kinases (FunK1) unique to multicellular fungi. Analyses of P450 and hydrophobin gene families confirmed that local gene duplications drive the expansions of paralogous copies and the expansions occur in independent lineages of Agaricomycotina fungi. Gene-expression patterns from microarrays were used to dissect the transcriptional program of dikaryon formation (mating). Several members of the FunK1 kinase family are differentially regulated during sexual morphogenesis, and coordinate regulation of adjacent duplications is rare. The genomes of C. cinerea and Laccaria bicolor, a symbiotic basidiomycete, share extensive regions of synteny. The largest syntenic blocks occur in regions with low meiotic recombination rates, no transposable elements, and tight gene spacing, where orthologous single-copy genes are overrepresented. The chromosome assembly of C. cinerea is an essential resource in understanding the evolution of multicellularity in the fungi.

Investigating dominant selection markers for Coprinopsis cinerea: a carboxin resistance system and re-evaluation of hygromycin and phleomycin resistance vectors.

Dominant selectable markers are beneficial for transformation of many fungi, particularly those model species where repeated transformations may be required. A carboxin resistance allele of the Coprinopsis cinerea sdi1 gene, encoding the iron-sulphur protein subunit of succinate dehydrogenase, was developed by introducing a suitable point mutation in the histidine block responsible for binding of the associated iron ion. This modified gene was used successfully to confer carboxin resistance upon transformation of C. cinerea protoplasts. Plasmids previously used to establish hygromycin transformation systems of several basidiomycete species, such as pAN7-1 and phph004, failed to give rise to hygromycin-resistant transformants of C. cinerea, whilst pPHT1 was successful. Sequencing of these constructs showed that the hygromycin resistance gene in pAN7-1 and phph004 had been modified removing the codons encoding two lysine residues following the N-terminal methionine. Replacement of the deleted 6 bp (AAA AAG) in the truncated hph gene led to generation of hygromycin-resistant transformants indicating the importance of these two codons for expression in C. cinerea. Phleomycin-resistant (ble) transformants were also obtained, but only with the intron-containing construct pblei004, showing that an intron is necessary to obtain phleomycin-resistant C. cinerea. This contrasts with hygromycin-resistance, where introns are not required for expression, emphasising the variability in importance of these elements.

Expression of laccase gene lcc1 in Coprinopsis cinerea under control of various basidiomycetous promoters.

Coprinopsis cinerea laccase gene lcc1 was expressed in this basidiomycete under naturally non-inductive conditions using various homologous and heterologous promoters. Laccase expression was achieved in solid and liquid media with promoter sequences from the C. cinerea tub1 gene, the Agaricus bisporus gpdII gene, the Lentinus edodes priA gene and the Schizophyllum commune Sc3 gene. As measured by enzyme activity in liquid cultures, a 277-bp gpdII promoter fragment, followed by a 423-bp priA fragment, was most efficient. A shorter priA sequence of 372 bp was inactive. tub1 promoter fragments were reasonably active, whereas the S. commune Sc3 promoter sequence was less active, in comparison. Irrespective of the promoter used, addition of copper to the medium increased enzymatic activities for highly active transformants by 10- to 50-fold and for less active transformants for 2- to 7-fold. The highest enzymatic activities (3 U/ml) were reached with the gpdII promoter in the presence of 0.1 mM CuSO(4).

The use of cusum analysis in the early detection and management of hospital bed occupancy crises.

OBJECTIVE: To assess the value of cusum analysis in hospital bed management. DESIGN: Comparative analysis of medical patient flows, bed occupancy, and emergency department admission rates and access block over 2 years. SETTING: Internal Medicine Services and Emergency Department in a teaching hospital. INTERVENTIONS: Improvements in bed use and changes in the level of available beds. MAIN OUTCOME MEASURES: Average length of stay; percentage occupancy of available beds; number of patients waiting more than 8 hours for admission (access block); number of medical patients occupying beds in non-medical wards; and number of elective surgical admissions. RESULTS: Cusum analysis provided a simple means of revealing important trends in patient flows that were not obvious in conventional time-series data. This prompted improvements in bed use that resulted in a decrease of 9500 occupied bed-days over a year. Unfortunately and unexpectedly, after some initial improvement, the levels of access block, medical ward congestion and elective surgical admissions all then deteriorated significantly. This was probably caused by excessive bed closures in response to the initial improvement in bed use. CONCLUSION: Cusum analysis is a useful technique for the early detection of significant changes in patient flows and bed use, and in determining the appropriate number of beds required for a given rate of patient flow.

Identification, cloning, and functional expression of three glutathione transferase genes from Aspergillus fumigatus.

Analysis of the genome of the human pathogen, Aspergillus fumigatus, revealed the presence of several putative glutathione transferase (GST) open reading frames. Three A. fumigatus GST genes, termed gstA, B, and C, were cloned and recombinant proteins expressed in Escherichia coli. Functional analysis of recombinant gstA-C confirms that the enzymes exhibit GST activity and glutathione peroxidase activity. RT-PCR confirmed low basal expression of gstA and gstC which was markedly up-regulated (at least 4x-10x) in the presence of either H2O2 or 1-chloro-2,4-dinitrobenzene (CDNB). GstB expression was only observed in the presence of CDNB. These results demonstrate for the first time the existence of three functional GSTs in A. fumigatus and strongly suggest a role for these enzymes in the response of the organism to both oxidative stress and xenobiotic presence.