De-Novo Discovery of Differentially Abundant Transcription Factor Binding Sites Including Their Positional Preference

Transcription factors are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in promoters. The de-novo discovery of transcription factor binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational biology, which has not been fully solved yet. Here, we present a de-novo motif discovery tool called Dispom for finding differentially abundant transcription factor binding sites that models existing positional preferences of binding sites and adjusts the length of the motif in the learning process. Evaluating Dispom, we find that its prediction performance is superior to existing tools for de-novo motif discovery for 18 benchmark data sets with planted binding sites, and for a metazoan compendium based on experimental data from micro-array, ChIP-chip, ChIP-DSL, and DamID as well as Gene Ontology data. Finally, we apply Dispom to find binding sites differentially abundant in promoters of auxin-responsive genes extracted from Arabidopsis thaliana microarray data, and we find a motif that can be interpreted as a refined auxin responsive element predominately positioned in the 250-bp region upstream of the transcription start site. Using an independent data set of auxin-responsive genes, we find in genome-wide predictions that the refined motif is more specific for auxin-responsive genes than the canonical auxin-responsive element. In general, Dispom can be used to find differentially abundant motifs in sequences of any origin. However, the positional distribution learned by Dispom is especially beneficial if all sequences are aligned to some anchor point like the transcription start site in case of promoter sequences. We demonstrate that the combination of searching for differentially abundant motifs and inferring a position distribution from the data is beneficial for de-novo motif discovery. Hence, we make the tool freely available as a component of the open-source Java framework Jstacs and as a stand-alone application at http://www.jstacs.de/index.php/Dispom

One foot in the rave: Ageing ravers’ transitions to adulthood and their participation in rave culture

Challenging adolescence limited life-course theory, this article presents the results of an online survey (2016) that aimed to establish if, how and to what extent ageing ravers continue to participate in rave culture. The survey collected data from members of the original rave generation. We explored the ravers’ transitions to adulthood, and how these influenced their participation in club culture. We found that our ravers continued to participate in rave culture; their persistence is related to the frequency of their engagement at a younger age. Adopting interdisciplinarity, we apply theories from both life course research and youth culture studies and argue that the persistence of leisure practices, such as raving, can be understood in the same way as persistence of drug use: frequent behavior in adolescence determines persistence in older adulthood. Consequently, we are able to recognize patterns of leisure beyond adolescence, thus making leisure choices more predictable

Preparation of Intravenous Stealthy Acyclovir Nanoparticles with Increased Mean Residence Time

A major cause of thromboplebitis, during acyclovir (ACV) parenteral administration is the high pH of its reconstituted solution (pH 11). Its plasma half life is 2.5 h, requiring repeated administration which may result in excess of drug solubility leading to possible renal damage and acute renal failure. The present study reports the efficiency of stealthy ACV nanoparticles (NPs) to increase the mean residence time of the drug 29 times. It caused a marked decrease in thrombophlebitis when injected into rabbit’s ear vein. The polymers used were (Poly lactic acid, polylactic-co-glycolic (PLGA) 85/15, PLGA 75/25, PLGA 50/50). Particles were evaluated for their encapsulation efficiency, morphology, particle size and size distribution, zeta potential, and in vitro drug release. Small NPs (280–300 nm) with 60% drug release after 48 h were obtained. Among the block copolymer used, poloxamer 407 was of superior coating properties with a coat thickness in the range of 1.5–8.3 nm and a decreased surface charge