Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer

We have used retrovirus-mediated gene transfer to demonstrate complementation of the cystic fibrosis (CF) defect in vitro. Amphotropic retroviruses were used to transduce a functional cystic fibrosis transmembrane conductance regulator (CFTR) cDNA into CFPAC-1, a pancreatic adenocarcinoma cell line derived from a patient with CF that stably expresses the chloride transport abnormalities characteristic of CF. CFPAC-1 cells were exposed to control virus (PLJ) and CFTR-expressing virus (PLJ-CFTR); viral-transduced clones were isolated and subjected to molecular and physiologic analysis. RNA analysis detected a viral-derived CFTR transcript in all of the PLJ-CFTR clones that contained unrearranged proviral sequences. Agents that increase intracellular cAMP stimulated 125I efflux in PLJ-CFTR clones but not PLJ clones. Whole-cell patch-clamp performed on three responding clones showed that the anion efflux responses were due to cAMP stimulation of Cl conductance. Our findings indicate that expression of the normal CFTR gene confers cAMP-dependent Cl channel regulation on CF epithelial cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28383/1/0000156.pd

Transcriptional Response of Zebrafish Embryos Exposed to Neurotoxic Compounds Reveals a Muscle Activity Dependent hspb11 Expression

Acetylcholinesterase (AChE) inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM), in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB) and 2,4-dinitrophenol (DNP). A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sopfixe mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR) activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds

Nutrient intakes and nutritional biomarkers in pregnant adolescents: a systematic review of studies in developed countries

Background: Babies born to adolescent mothers have been shown to have poorer outcomes compared to those born to adults. Nutritional status may have an important role to play in improving the health of pregnant adolescents; however there is a lack of evidence regarding the adequacy of adolescent diets during pregnancy. This systematic review aims to examine what is known about the nutritional status of adolescent pregnant women. Methods: A systematic search of the literature identified 21 studies which met the inclusion criteria for the review. Primary research papers using any methods were included where they were published in English between January 1995 and May 2015 and included measurements of nutrient intakes or biological markers of nutritional status in pregnant women aged 11-19 years. Individual study data was first summarised narratively before study means were pooled to give an estimate of nutritional status in the population. Results: The results show that individual studies reported intakes of energy, fibre and a number of key micronutrients which were below recommended levels. Biological markers of iron and selenium status also showed cause for concern. Pooled analysis of individual means as a percentage of UK Dietary Reference Intakes showed intakes of vitamin D (34.8 % CI 0-83.1) to be significantly below recommendations (p=0.05). Serum selenium levels were also found to be low (61.8 μg/L, CI 39-84). Conclusions: This review has identified a number of areas where the nutritional status of pregnant adolescents is sub-optimal, which may have implications for the health of adolescent mothers and their babies. It was not however possible to examine the impact of supplement use or socio-demographic characteristics which limits the interpretation these results. Further work is needed to establish the characteristics of those most at risk within this population, how this differs from adult pregnant women and the role of supplementation in achieving adequate nutrition

Competition and Combative Advertising: An Historical Analysis

Fred K. Beard (PhD, University of Oklahoma) is a professor of advertising in the Gaylord College of Journalism and Mass Communication, University of Oklahoma. His research interests include comparative advertising, advertising humor, and advertising history. His work has appeared in the Journal of Advertising, the Journal of Advertising Research, the Journal of Business Ethics, the Journal of Business Research, Journalism History, the Journal of Historical Research in Marketing, the Journal of Macromarketing, and the Journal of Marketing Communications, among others.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The Anchor Bible : V.15.: Job

New Yorklxxxix, 409 p.; 24 cm

The Anchor Bible : Job

New Yorklxxxiv , 406 p. ; 24 c