1. {{[The role of ZF5 and CGGBP-20 transcription factors in expression regulation of human FMR1 gene responsible for X-fragile syndrome]}}. {Tsitologiia};2009;51(12):1005-1012.
The human FMR1 gene encodes an RNA-binding protein taking part in translation regulation. The 5′-untranslated region of FMR1 gene contains a large number of tandem repeats of GCC triplets (5-50) which increasing (more then 200) is responsible for X-fragile syndrome (human congenital anomaly). As it has been shown earlier, al least two transcription factors (ZF5 and CGGBP-20) are capable of interacting specifically with GCC-repeats in regulatory regions of some genes. In this work, their roles in FMR1 gene expression regulation were studied. It was demonstrated by electrophoretic mobility shift assay that ZF5 recombinant protein specifically bound with GCC-triplet repeats (GCC9). Tissue-specific distributions of ZF5 and FMR1 proteins are very overlapped in mammalian. Inhibition of ZF5 expression in HepG2 cells (by RNA interference) leads to at least 1.5 times stimulations of FMR1 gene expression in these cells. To estimate the contribution of GCC-triplet repeats in FMR1 gene expression regulation we used two alternative variants of genetic construction: containing luciferase reporter gene under 5′-regulatory region fragment devoid of GCC-triplet repeats or including the GCC9 nucleotide sequence. HepG2 cells were co-transfected by these constructions and expressions vectors of ZF5 or (and) CGGBP-20 respectively. It was found that ZF5 downregulated the activity of 5′-regulatory region of FMR1 gene in both cases (acting probably through canonic 5′-GCGCGC3′ sites). The presence of GCC-triplet repeats in the construction weakens this ZF5 effect. CGGBP-20 downregulates the activity of 5′-region of FMR1 gene in the presence of GCC-triplets only. The data obtained evidently indicate differently directed ZF5 effects on FMR1 gene expression and suggest the mechanism to explain the earlier demonstrated phenomenon about increasing of mRNA level in permutation FMR1 allele carries.
2. Chevallier C, Wilson D, Happe F, Noveck I. {{Scalar Inferences in Autism Spectrum Disorders}}. {J Autism Dev Disord} (Feb 9)
On being told « John or Mary will come », one might infer that not both of them will come. Yet the semantics of « or » is compatible with a situation where both John and Mary come. Inferences of this type, which enrich the semantics of « or » from an ‘inclusive’ to an ‘exclusive’ interpretation, have been extensively studied in linguistic pragmatics. However, the phenomenon has not been much explored in Autism Spectrum Disorders (ASDs), where pragmatic deficits are commonly reported. Here, we present an experiment investigating these inferences. We predicted that, as a result of the reported pragmatic deficits, participants with ASD would produce fewer inferential enrichments of « or » than matched controls. However, contrary to expectations, but in line with recent findings by Pijnacker et al. (Journal of Autism and Developmental Disorders, 39, 607-618, 2009), performances did not differ across groups. This unexpected finding is discussed in light of the literature on pragmatic abilities in autism.
3. Eggertson L. {{Lancet retracts 12-year-old article linking autism to MMR vaccines}}. {Cmaj} (Feb 8)
4. Foley Nicpon M, Doobay AF, Assouline SG. {{Parent, Teacher, and Self Perceptions of Psychosocial Functioning in Intellectually Gifted Children and Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord} (Feb 9)
Parent, teacher, and self-perceptions of 54 high ability students with autism spectrum disorder (ASD) were assessed through administration of the Behavioral Assessment Scales for Children, Second Edition. Parent reports resulted in clinically elevated scores on the Atypicality, Attention Problems, Depression, Hyperactivity, Withdrawal, Activities of Daily Living, Adaptability, and Social Skills subscales, and teacher reports resulted in clinically elevated scores on the Atypicality, Depression, Withdrawal, and Adaptability subscales. Self-report scores were in the average range. Parents and teachers of adolescents reported greater adaptability and fewer symptoms of atypicality than parents and teachers of children. Psychosocial functioning appears impacted in high ability students with ASD and developmental differences in severity may exist.
5. Guttmann-Steinmetz S, Gadow KD, Devincent CJ, Crowell J. {{Anxiety Symptoms in Boys with Autism Spectrum Disorder, Attention-Deficit Hyperactivity Disorder, or Chronic Multiple Tic Disorder and Community Controls}}. {J Autism Dev Disord} (Feb 9)
We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) in 5 groups of boys with neurobehavioral syndromes: attention-deficit/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD plus chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community Controls. Anxiety symptoms were assessed using parent and teacher versions of a DSM-IV-referenced rating scale. All three groups of boys with co-morbid ADHD evidenced more severe anxiety than Controls. Group differences in anxiety varied as a function of symptom, disorder, informant, and co-morbidity supporting the notion that co-morbid neurobehavioral syndromes differentially impact clinical features of co-occurring anxiety symptoms. Findings also suggest that GAD and SAD are phenomenologically unique, even in children with ASD. Implications for nosology are discussed.
6. Martirosian G. {{[Clostridium spp. spores in pathomechanism of autism]}}. {Wiad Lek};2009;62(2):119-122.Spory bakterii Clostridium spp. w patomechanizmie autyzmu.
Autism is a syndrom with unknown etiology, however many hypothesis are described in medical publications. These hypothesis include clostridial spores as key elements. Exo- and also endogenous spores are possible cause of autism: antibiotics have lack of effects on spores, which germinate after discontinuation of antibiotic therapy to vegetative neurotoxin producing forms. In this paper we discuss possible role of gastrointestinal tract and intestinal microflora in pathomechanism of autism on the light of recent publications.
7. Shelton JF, Tancredi DJ, Hertz-Picciotto I. {{Independent and dependent contributions of advanced maternal and paternal ages to autism risk}}. {Autism Res} (Feb 8)
Reports on autism and parental age have yielded conflicting results on whether mothers, fathers, or both, contribute to increased risk. We analyzed restricted strata of parental age in a 10-year California birth cohort to determine the independent or dependent effect from each parent. Autism cases from California Department of Developmental Services records were linked to State birth files (1990-1999). Only singleton births with complete data on parental age and education were included (n=4,947,935, cases=12,159). In multivariate logistic regression models, advancing maternal age increased risk for autism monotonically regardless of the paternal age. Compared with mothers 25-29 years of age, the adjusted odds ratio (aOR) for mothers 40+ years was 1.51 (95% CI: 1.35-1.70), or compared with mothers <25 years of age, aOR=1.77 (95% CI, 1.56-2.00). In contrast, autism risk was associated with advancing paternal age primarily among mothers <30: aOR=1.59 (95% CI, 1.37-1.85) comparing fathers 40+ vs. 25-29 years of age. However, among mothers >30, the aOR was 1.13 (95% CI, 1.01-1.27) for fathers 40+ vs. 25-29 years of age, almost identical to the aOR for fathers <25 years. Based on the first examination of heterogeneity in parental age effects, it appears that women’s risk for delivering a child who develops autism increases throughout their reproductive years whereas father’s age confers increased risk for autism when mothers are <30, but has little effect when mothers are past age 30. We also calculated that the recent trend towards delayed childbearing contributed approximately a 4.6% increase in autism diagnoses in California over the decade.
