Mucin Variable Number Tandem Repeat Polymorphisms and Severity of Cystic Fibrosis Lung Disease: Significant Association with MUC5AC

Variability in cystic fibrosis (CF) lung disease is partially due to non-CFTR genetic modifiers. Mucin genes are very polymorphic, and mucins play a key role in the pathogenesis of CF lung disease; therefore, mucin genes are strong candidates as genetic modifiers. DNA from CF patients recruited for extremes of lung phenotype was analyzed by Southern blot or PCR to define variable number tandem repeat (VNTR) length polymorphisms for MUC1, MUC2, MUC5AC, and MUC7. VNTR length polymorphisms were tested for association with lung disease severity and for linkage disequilibrium (LD) with flanking single nucleotide polymorphisms (SNPs). No strong associations were found for MUC1, MUC2, or MUC7. A significant association was found between the overall distribution of MUC5AC VNTR length and CF lung disease severity (p = 0.025; n = 468 patients); plus, there was robust association of the specific 6.4 kb HinfI VNTR fragment with severity of lung disease (p = 6.2 x 10(-4) after Bonferroni correction). There was strong LD between MUC5AC VNTR length modes and flanking SNPs. The severity-associated 6.4 kb VNTR allele of MUC5AC was confirmed to be genetically distinct from the 6.3 kb allele, as it showed significantly stronger association with nearby SNPs. These data provide detailed respiratory mucin gene VNTR allele distributions in CF patients. Our data also show a novel link between the MUC5AC 6.4 kb VNTR allele and severity of CF lung disease. The LD pattern with surrounding SNPs suggests that the 6.4 kb allele contains, or is linked to, important functional genetic variation

Tribally Controlled Community College Libraries: A Paradigm for Survival

published or submitted for publicatio

“Hunting with a knife and … fork”: Examining central coherence in autism, attention deficit/hyperactivity disorder, and typical development with a linguistic task

A local processing bias, referred to as “weak central coherence,” has been postulated to underlie key aspects of autism spectrum disorder (ASD). Little research has examined whether individual differences in this cognitive style can be found in typical development, independent of intelligence, and how local processing relates to executive control. We present a brief and easy-to-administer test of coherence requiring global sentence completions. We report results from three studies assessing (a) 176 typically developing (TD) 8- to 25-year-olds, (b) individuals with ASD and matched controls, and (c) matched groups with ASD or attention deficit/hyperactivity disorder (ADHD). The results suggest that the Sentence Completion Task can reveal individual differences in cognitive style unrelated to IQ in typical development, that most (but not all) people with ASD show weak coherence on this task, and that performance is not related to inhibitory control. The Sentence Completion Task was found to be a useful test instrument, capable of tapping local processing bias in a range of populations

3.3-million-year-old stone tools from Lomekwi 3, West Turkana, Kenya

International audienceHuman evolutionary scholars have long supposed that the earliest stone tools were made by the genus Homo and that this technological development was directly linked to climate change and the spread of savannah grasslands. New fieldwork in West Turkana, Kenya, has identified evidence of much earlier hominin technological behaviour. We report the discovery of Lomekwi 3, a 3.3-million-year-old archaeological site where in situ stone artefacts occur in spatiotemporal association with Pliocene hominin fossils in a wooded palaeoenvironment. The Lomekwi 3 knappers, with a developing understanding of stone’s fracture properties, combined core reduction with battering activities. Given the implications of the Lomekwi 3 assemblage for models aiming to converge environmental change, hominin evolution and technological origins, we propose for it the name ‘Lomekwian’, which predates the Oldowan by 700,000 years and marks a new beginning to the known archaeological record