Bisubstrate-Type Chemical Probes Identify GRP94 as a Potential Target of Cytosine-Containing Adenosine Analogs.

We synthesized affinity-based chemical probes of cytosine-adenosine bisubstrate analogs and identified several potential targets by proteomic analysis. The validation of the proteomic analysis identified the chemical probe as a specific inhibitor of glucose-regulated protein 94 (GRP94), a potential drug target for several types of cancers. Therefore, as a result of the use of bisubstrate-type chemical probes and a chemical-biology methodology, this work opens the way to the development of a new family of GRP94 inhibitors that could potentially be of therapeutic interest.

Quantum Rabi Oscillations in Coherent and in Mesoscopic Cat Field States.

The simple resonant Rabi oscillation of a two-level system in a single-mode coherent field reveals complex features at the mesoscopic scale, with oscillation collapses and revivals. Using slow circular Rydberg atoms interacting with a superconducting microwave cavity, we explore this phenomenon in an unprecedented range of interaction times and photon numbers. We demonstrate the efficient production of cat states, which are the quantum superposition of coherent components with nearly opposite phases and sizes in the range of few tens of photons.

DNA Methylation Analysis of ChIP Products at Single Nucleotide Resolution by Pyrosequencing®.

Interaction and co-occurrence of protein and DNA-based epigenetic modifications have become a topic of interest for many fundamental and biomedical questions. We describe within this chapter a protocol that combines two techniques in order to determine the methylation status of the DNA specifically associated with a protein of interest. First, DNA that directly interacts with the selected protein (such as a specific histone modification, a transcription factor, or any other DNA-associated protein) is purified by standard chromatin immunoprecipitation (ChIP).

Synergistic chromatin repression of the tumor suppressor gene RARB in human prostate cancers.

DNA methylation and polycomb proteins are well-known mediators of epigenetic silencing in mammalian cells. Usually described as mutually exclusive, this statement is today controversial and recent in vitro studies suggest the co-existence of both repressor systems. We addressed this issue in the study of Retinoic Acid Receptor β (RARβ), a tumor suppressor gene frequently silenced in prostate cancer.

Aquatic hyphomycete species are screened by the hyporheic zone of woodland streams.

Aquatic hyphomycetes strongly contribute to organic matter dynamics in streams, but their abilities to colonize leaf litter buried in streambed sediments remain unexplored. Here, we conducted field and laboratory experiments (slow-filtration columns and stream-simulating microcosms) to test the following hypotheses: (i) that the hyporheic habitat acting as a physical sieve for spores filters out unsuccessful strategists from a potential species pool, (ii) that decreased pore size in sediments reduces species dispersal efficiency in the interstitial water, and (iii) that the physicochemical conditions prevailing in the hyporheic habitat will influence fungal community structure. Our field study showed that spore abundance and species diversity were consistently reduced in the interstitial water compared with surface water within three differing streams.