Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: From treatment to prevention

The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being

Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation

A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilitated a rapid growth of their use and resulted in their ubiquity in complex organisms. The ease of motif acquisition simplifies access to basal housekeeping functions, facilitates the co-regulation of multiple biomolecules allowing them to respond in a coordinated manner to changes in the cell state, and supports the integration of multiple signals for combinatorial decision-making. Consequently, motifs are indispensable for temporal, spatial, conditional and basal regulation at the transcriptional, post-transcriptional and post-translational level. In this review, we highlight that many of the key regulatory pathways of the cell are recruited by motifs and that the ease of motif acquisition has resulted in large networks of co-regulated biomolecules. We discuss how co-operativity allows simple static motifs to perform the conditional regulation that underlies decision-making in higher eukaryotic biological systems. We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules

Chemical flushing from an urban-fringe watershed: Hydrologic and riparian soil dynamics

The goal of the current study is to better understand the role of storm dynamics on stream water chemical variability in a highly polluted urban-fringe watershed. The study was conducted in the upper reach of the Arroyo Seco watershed located on the eastern edge of the densely urbanized Los Angeles basin in California. During the 2008-2009 study period, high-frequency stream water observations of chloride, fluoride, sulfate, and nitrate were monitored through a series of storm events and were compared to pre- and post-winter storm season geochemical soil profiles. Of the four solutes measured, nitrate demonstrated hydrologically enhanced behavior. Chloride, fluoride, and sulfate exhibited enhanced behavior initially (first flush), but transitioned to dilution behavior as the season progressed. Soil chemistry analyses in the riparian zone confirmed the abundance of nitrate on the soil surface, serving as a source for stream water nitrate. Observations and analyses collectively suggest that the chemical variability observed during the storms is dependent not only on discharge, but also on the magnitude and intensity of rainfall, the length of the antecedent dry period, and riparian soil composition. A further understanding of these factors will ultimately improve geochemical models for prediction of downstream chemical loads from regional urban-fringe watersheds. © 2013 Springer-Verlag Berlin Heidelberg

Trends in surface water chemistry in acidified areas in Europe and North America from 1990 to 2008

Acidification of lakes and rivers is still an environmental concern despite reduced emissions of acidifying compounds. We analysed trends in surface water chemistry of 173 acid-sensitive sites from 12 regions in Europe and North America. In 11 of 12 regions, non-marine sulphate (SO4*) declined significantly between 1990 and 2008 (−15 to −59 %). In contrast, regional and temporal trends in nitrate were smaller and less uniform. In 11 of 12 regions, chemical recovery was demonstrated in the form of positive trends in pH and/or alkalinity and/or acid neutralising capacity (ANC). The positive trends in these indicators of chemical recovery were regionally and temporally less distinct than the decline in SO4* and tended to flatten after 1999. From an ecological perspective, the chemical quality of surface waters in acid-sensitive areas in these regions has clearly improved as a consequence of emission abatement strategies, paving the way for some biological recovery