Study of FoxA Pioneer Factor at Silent Genes Reveals Rfx-Repressed Enhancer at Cdx2 and a Potential Indicator of Esophageal Adenocarcinoma Development

Understanding how silent genes can be competent for activation provides insight into development as well as cellular reprogramming and pathogenesis. We performed genomic location analysis of the pioneer transcription factor FoxA in the adult mouse liver and found that about one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. Virtually all of the FoxA-bound silent sites are within conserved sequences, suggesting possible function. Such sites are enriched in motifs for transcriptional repressors, including for Rfx1 and type II nuclear hormone receptors. We found one such target site at a cryptic “shadow” enhancer 7 kilobases (kb) downstream of the Cdx2 gene, where Rfx1 restricts transcriptional activation by FoxA. The Cdx2 shadow enhancer exhibits a subset of regulatory properties of the upstream Cdx2 promoter region. While Cdx2 is ectopically induced in the early metaplastic condition of Barrett's esophagus, its expression is not necessarily present in progressive Barrett's with dysplasia or adenocarcinoma. By contrast, we find that Rfx1 expression in the esophageal epithelium becomes gradually extinguished during progression to cancer, i.e, expression of Rfx1 decreased markedly in dysplasia and adenocarcinoma. We propose that this decreased expression of Rfx1 could be an indicator of progression from Barrett's esophagus to adenocarcinoma and that similar analyses of other transcription factors bound to silent genes can reveal unanticipated regulatory insights into oncogenic progression and cellular reprogramming

Estimates of new and total productivity in central Long Island Sound from in situ measurements of nitrate and dissolved oxygen

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Estuaries and Coasts 36 (2013): 74-97, doi:10.1007/s12237-012-9560-5.Biogeochemical cycles in estuaries are regulated by a diverse set of physical and biological variables that operate over a variety of time scales. Using in situ optical sensors, we conducted a high-frequency time-series study of several biogeochemical parameters at a mooring in central Long Island Sound from May to August 2010. During this period, we documented well-defined diel cycles in nitrate concentration that were correlated to dissolved oxygen, wind stress, tidal mixing, and irradiance. By filtering the data to separate the nitrate time series into various signal components, we estimated the amount of variation that could be ascribed to each process. Primary production and surface wind stress explained 59% and 19%, respectively, of the variation in nitrate concentrations. Less frequent physical forcings, including large-magnitude wind events and spring tides, served to decouple the relationship between oxygen, nitrate, and sunlight on about one-quarter of study days. Daytime nitrate minima and dissolved oxygen maxima occurred nearly simultaneously on the majority (> 80%) of days during the study period; both were strongly correlated with the daily peak in irradiance. Nighttime nitrate maxima reflected a pattern in which surface-layer stocks were depleted each afternoon and recharged the following night. Changes in nitrate concentrations were used to generate daily estimates of new primary production (182 ± 37 mg C m-2 d-1) and the f-ratio (0.25), i.e., the ratio of production based on nitrate to total production. These estimates, the first of their kind in Long Island Sound, were compared to values of community respiration, primary productivity, and net ecosystem metabolism, which were derived from in situ measurements of oxygen concentration. Daily averages of the three metabolic parameters were 1660 ± 431, 2080 ± 419, and 429 ± 203 mg C m-2 d-1, respectively. While the system remained weakly autotrophic over the duration of the study period, we observed very large day-to-day differences in the f-ratio and in the various metabolic parameters.This work was supported by the Yale Institute for Biospheric Studies, the Sounds Conservancy of the Quebec-Labrador Foundation, and the Yale School of Forestry and Environmental Studies Carpenter-Sperry Fund.2014-01-0

Stable isotopic evidence for nitrification and denitrification in a High Arctic glacial ecosystem

Solute chemistry and stable isotope tracers of NO3 − were used to assess bacterial NO3 − production and denitrification in a High Arctic glacial ecosystem during 2009. Changes in the NO3 − concentration and the δ18O–NO3 in all the proglacial streams revealed that up to 95 % of total NO3 − was most likely bacterially-derived during low flow conditions towards the end of the summer (day of year 250). However, overlapping ranges of δ15N values for snow NH4 +, soil organic matter, cryoconite debris and geological nitrogen in host rocks mean that neither the preferred substrate(s), nor the pathway (i.e. nitrification or simple mineralisation) can be discerned. The most plausible explanation for the bacterial production of NO3 − is nitrification in snowmelt-fed flowpaths through avalanche fans that flank the glacier and along subglacial drainage pathways at the glacier bed. Interestingly, there was no evidence for denitrification in subglacial outflow, which is contrary to earlier research at this site. Instead, increases in the δ15N–NO3 of up to 20 ‰ downstream of the glacier margin, suggests that denitrification in the glacier forefield and/or the sediments that flank it was most discernable during 2009. Our observations therefore suggest that poorly understood temporal variations in the mixing ratio of nitrifying and denitrifying flowpaths occur in this glacial ecosystem

The Effect of Parenting Style on Social Smiling in Infants at High and Low Risk for ASD

This study examined how parenting style at 9 months predicts growth in infant social engagement (i.e., social smiling) between 9 and 18 months during a free-play interaction in infants at high (HR-infants) and low (LR-infants) familial risk for Autism Spectrum Disorder (ASD). Results indicated that across all infants, higher levels of maternal responsiveness were concurrently associated with higher levels of social smiling, while higher levels of maternal directiveness predicted slower growth in social smiling. When accounting for maternal directiveness, which was higher in mothers of HR-infants, HR-infants exhibited greater growth in social smiling than LR-infants. Overall, each parenting style appears to make a unique contribution to the development of social engagement in infants at high- and low-risk for ASD

Wittgenstein's Method of Conceptual Investigation and Concept Formation in Psychology

Recent work in social robotics, which is aimed both at creating an artificial intelligence and providing a test-bed for psychological theories of human social development, involves building robots that can learn from ‘face-to-face’ interaction with human beings — as human infants do. The building-blocks of this interaction include the robot’s ‘expressive’ behaviours, for example, facial-expression and head-and-neck gesture. There is here an ideal opportunity to apply Wittgensteinian conceptual analysis to current theoretical and empirical work in the sciences. Wittgenstein’s philosophical psychology is sympathetic to embodied and situated Artificial Intelligence (see Proudfoot, 2002, 2004b), and his discussion of facial-expression is remarkably modern. In this chapter, I explore his approach to facial-expression, using smiling as a representative example, and apply it to the canonical interactive face robot, Cynthia Breazeal’s Kismet (see e.g. Breazeal, 2009, 2002). I assess the claim that Kismet has expressive behaviours, with the aim of generating philosophical insights for AI