Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2

Towards understanding the traits contributing to performance of pearl millet open-pollinated varieties in phosphorus-limited environments of West Africa

Aims Pearl millet [Pennisetum glaucum (L.) R. Br.] open-pollinated varieties, which are the predominant cultivars, have never been systematically evaluated for adaptation to low-soil phosphorus (P), a major constraint on pearl millet production in West Africa (WA). Methods We evaluated grain yield (GY), flowering time (FLO), harvest index (HI), and residual grain yields (RGY) of 102 open-pollinated varieties from WA under low-P (−P) and high-P (+P) field conditions in six environments of WA. In addition, PE-related traits of the varieties were evaluated at early growth stage in a pot experiment. Results Significant genetic variation was observed for GY, FLO, HI and PE-related traits. P-efficient varieties had higher yield under −P conditions. Varietal performance under −P varied across environments depending on FLO, relative flowering delay under −P (FD) and RGY measured in the field. Low-P-susceptible varieties had higher FLO, lower HI than low-P-tolerant varieties. Response to direct selection under −P field conditions was 20.1 g m−2, whereas indirect selection response under +P was 16.3 g m−2. Conclusions Selection under −P field conditions while taking into account seasonal variations for FLO, FD and PE is expected to be important for improving GY specifically targeting −P environments in WA

Spectroscopy of short-lived radioactive molecules

Molecular spectroscopy offers opportunities for the exploration of the fundamental laws of nature and the search for new particle physics beyond the standard model1-4. Radioactive molecules-in which one or more of the atoms possesses a radioactive nucleus-can contain heavy and deformed nuclei, offering high sensitivity for investigating parity- and time-reversal-violation effects5,6. Radium monofluoride, RaF, is of particular interest because it is predicted to have an electronic structure appropriate for laser cooling6, thus paving the way for its use in high-precision spectroscopic studies. Furthermore, the effects of symmetry-violating nuclear moments are strongly enhanced5,7-9 in molecules containing octupole-deformed radium isotopes10,11. However, the study of RaF has been impeded by the lack of stable isotopes of radium. Here we present an experimental approach to studying short-lived radioactive molecules, which allows us to measure molecules with lifetimes of just tens of milliseconds. Energetically low-lying electronic states were measured for different isotopically pure RaF molecules using collinear resonance ionisation at the ISOLDE ion-beam facility at CERN. Our results provide evidence of the existence of a suitable laser-cooling scheme for these molecules and represent a key step towards high-precision studies in these systems. Our findings will enable further studies of short-lived radioactive molecules for fundamental physics research.status: publishe

Spectroscopy of short-lived radioactive molecules

© 2020, The Author(s). Molecular spectroscopy offers opportunities for the exploration of the fundamental laws of nature and the search for new particle physics beyond the standard model1–4. Radioactive molecules—in which one or more of the atoms possesses a radioactive nucleus—can contain heavy and deformed nuclei, offering high sensitivity for investigating parity- and time-reversal-violation effects5,6. Radium monofluoride, RaF, is of particular interest because it is predicted to have an electronic structure appropriate for laser cooling6, thus paving the way for its use in high-precision spectroscopic studies. Furthermore, the effects of symmetry-violating nuclear moments are strongly enhanced5,7–9 in molecules containing octupole-deformed radium isotopes10,11. However, the study of RaF has been impeded by the lack of stable isotopes of radium. Here we present an experimental approach to studying short-lived radioactive molecules, which allows us to measure molecules with lifetimes of just tens of milliseconds. Energetically low-lying electronic states were measured for different isotopically pure RaF molecules using collinear resonance ionisation at the ISOLDE ion-beam facility at CERN. Our results provide evidence of the existence of a suitable laser-cooling scheme for these molecules and represent a key step towards high-precision studies in these systems. Our findings will enable further studies of short-lived radioactive molecules for fundamental physics research