Discovery of a Novel Bromodomain and Extra Terminal Domain (BET) Protein Inhibitor, I-BET282E, Suitable for Clinical Progression.

The functions of the bromodomain and extra terminal (BET) family of proteins have been implicated in a wide range of diseases, particularly in the oncology and immuno-inflammatory areas, and several inhibitors are under investigation in the clinic. To mitigate the risk of attrition of these compounds due to structurally related toxicity findings, additional molecules from distinct chemical series were required. Here we describe the structure- and property-based optimization of the tool molecule I-BET151 toward I-BET282E, a molecule with properties suitable for progression into clinical studies.

Assessing Cumulative Effects of Climate Change Manipulations on Phosphorus Limitation in a Californian Grassland.

Grasslands throughout the world are responding in diverse ways to changing climate and environmental conditions. In this study we analyze indicators of phosphorus limitation including phosphorus concentrations, phosphorus to nitrogen, and carbon ratios, oxygen isotope ratios of phosphate in vegetation, and phosphatase enzyme activity in soil to shed light on potential effects of climate change on phosphorus availability to grassland vegetation. The study was conducted at the Jasper Ridge Global Change Experiment (JRGCE), California where manipulations mimicking increases in temperature, water, nitrogen and carbon-dioxide have been maintained for over 15 years.

Using Continuous Underway Isotope Measurements To Map Water Residence Time in Hydrodynamically Complex Tidal Environments.

Stable isotopes present in water (δH, δO) have been used extensively to evaluate hydrological processes on the basis of parameters such as evaporation, precipitation, mixing, and residence time. In estuarine aquatic habitats, residence time (τ) is a major driver of biogeochemical processes, affecting trophic subsidies and conditions in fish-spawning habitats. But τ is highly variable in estuaries, owing to constant changes in river inflows, tides, wind, and water height, all of which combine to affect τ in unpredictable ways.

Isotope-ratio infrared spectroscopy: a reliable tool for the investigation of plant-water sources?

Stable isotopes are extensively used as tracers for the study of plant-water sources. Isotope-ratio infrared spectroscopy (IRIS) offers a cheaper alternative to isotope-ratio mass spectroscopy (IRMS), but its use in studying plant and soil water is limited by the spectral interference caused by organic contaminants. Here, we examine two approaches to cope with contaminated samples in IRIS: on-line oxidation of organic compounds (MCM) and post-processing correction.