A cognitive transition underlying both technological and social aspects of cumulative culture.

The argument that cumulative technological culture originates in technical-reasoning skills is not the only alternative to social accounts; another possibility is that accumulation of both technical-reasoning skills and enhanced social skills stemmed from the onset of a more basic cognitive ability such as recursive representational redescription. The paper confuses individual learning of pre-existing information with creative generation of new information.

Bilateral parietal contributions to spatial language.

It is commonly held that language is largely lateralized to the left hemisphere in most individuals, whereas spatial processing is associated with right hemisphere regions. In recent years, a number of neuroimaging studies have yielded conflicting results regarding the role of language and spatial processing areas in processing language about space (e.g., Carpenter, Just, Keller, Eddy, & Thulborn, 1999; Damasio et al., 2001). In the present study, we used sparse scanning event-related functional magnetic resonance imaging (fMRI) to investigate the neural correlates of spatial language, that is; language used to communicate the spatial relationship of one object to another. During scanning, participants listened to sentences about object relationships that were either spatial or non-spatial in nature (color or size relationships). Sentences describing spatial relationships elicited more activation in the superior parietal lobule and precuneus bilaterally in comparison to sentences describing size or color relationships. Activation of the precuneus suggests that spatial sentences elicit spatial-mental imagery, while the activation of the SPL suggests sentences containing spatial language involve integration of two distinct sets of information - linguistic and spatial.

Impact of gastro-oesophageal reflux on microRNA expression, location and function.

BACKGROUND: Ulceration of the oesophageal squamous mucosa (ulcerative oesophagitis) is a pathological manifestation of gastro-oesophageal reflux disease, and is a major risk factor for the development of Barrett's oesophagus. Barrett's oesophagus is characterised by replacement of reflux-damaged oesophageal squamous epithelium with a columnar intestinal-like epithelium. We previously reported discovery of microRNAs that are differentially expressed between oesophageal squamous mucosa and Barrett's oesophagus mucosa. Now, to better understand early steps in the initiation of Barrett's oesophagus, we assessed the expression, location and function of these microRNAs in oesophageal squamous mucosa from individuals with ulcerative oesophagitis. METHODS: Quantitative real-time PCR was used to compare miR-21, 143, 145, 194, 203, 205 and 215 expression levels in oesophageal mucosa from individuals without pathological gastro-oesophageal reflux to individuals with ulcerative oesophagitis. Correlations between microRNA expression and messenger RNA differentiation markers BMP-4, CK8 and CK14 were analyzed. The cellular localisation of microRNAs within the oesophageal mucosa was determined using in-situ hybridisation. microRNA involvement in proliferation and apoptosis was assessed following transfection of a human squamous oesophageal mucosal cell line (Het-1A). RESULTS: miR-143, miR-145 and miR-205 levels were significantly higher in gastro-oesophageal reflux compared with controls. Elevated miR-143 expression correlated with BMP-4 and CK8 expression, and elevated miR-205 expression correlated negatively with CK14 expression. Endogenous miR-143, miR-145 and miR-205 expression was localised to the basal layer of the oesophageal epithelium. Transfection of miR-143, 145 and 205 mimics into Het-1A cells resulted in increased apoptosis and decreased proliferation. CONCLUSIONS: Elevated miR-143, miR-145 and miR-205 expression was observed in oesophageal squamous mucosa of individuals with ulcerative oesophagitis. These miRNAs localised to the basal layer of the oesophageal epithelium. They reduced proliferation and increased apoptosis, and may play roles in regulating epithelial restoration in response to injury caused by gastro-oesophageal reflux.

miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus.

AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenal epithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed significant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium.

MicroRNAs, development of Barrett's esophagus, and progression to esophageal adenocarcinoma.

Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esophageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellular processes, and the role of miRNAs in disease development is becoming increasingly evident. Understanding altered miRNA expression is likely to help unravel the molecular mechanisms that underpin the development of Barrett's esophagus and its progression to cancer.