University of Medicine and Dentistry of New Jersey

About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Pregnancy. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.

Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation

Abstract: Polyadenylation is an essential step for the maturation of almost all cellular mRNAs in eukaryotes. In human cells, most poly(A) sites are flanked by the upstream AAUAAA hexamer or a close variant, and downstream U/GU-rich elements. In yeast and plants, additional cis elements have been found to be located upstream of the poly(A) site, including UGUA, UAUA, and U-rich elements. In this study, we have developed a computer program named PROBE (Polyadenylation-Related Oligonucleotide Bidimensional Enrichment) to identify cis elements that may play regulatory roles in mRNA polyadenylation. By comparing human genomic sequences surrounding frequently used poly(A) sites with those surrounding less frequently used ones, we found that cis elements occurring in yeast and plants also exist in human poly(A) regions, including the upstream U-rich elements, and UAUA and UGUA elements. In addition, several novel elements were found to be associated with human poly(A) sites, including several G-rich elements. Thus, we suggest that many cis elements are evolutionarily conserved among eukaryotes, and human poly(A) sites have an additional set of cis elements that may be involved in the regulation of mRNA polyadenylation.

Inhaled corticosteroids: past lessons and future issues

Abstract: Inhaled corticosteroids play a pivotal role in the treatment of asthma. Inhalation permits effective delivery of the corticosteroid in high concentration to target sites within the lung while minimizing systemic exposure. Consequently, the safety profile of inhaled corticosteroids is markedly better than that of oral corticosteroid therapy. However, although it was first thought that direct delivery might eliminate systemic adverse effects, this has not been confirmed by clinical trials and experience. Inhaled corticosteroids are absorbed from the lungs into the systemic circulation, in which they can acutely decrease growth velocity in children, an effect that fortunately appears to be temporary and might have no effect on final adult height. In sufficient dosages, they also produce bone mineral loss leading to osteoporosis and might increase the risk of cataracts, glaucoma, skin atrophy, and vascular changes that increase the risk of ecchymoses. Effective evaluation of the severity and significance of these complications is challenging because highly sensitive tests do not reliably predict clinically significant events, and short-term observations do not predict long-term consequences. Also, compliance wanes with long-term treatment, and susceptibility to a particular adverse event can vary over time, even in the same individual, because of developmental or hormonal changes. This journal supplement will review what has been learned about the safety of inhaled cortico-steroids during the past decade, discussing some of the questions that remain and considering the characteristics of an "ideal" inhaled corticosteroid: one with high local activity in the lung and minimal or no adverse systemic effects.