The Role of Response Elements Organization in Transcription Factor Selectivity: The IFN-β Enhanceosome Example

What is the mechanism through which transcription factors (TFs) assemble specifically along the enhancer DNA? The IFN-β enhanceosome provides a good model system: it is small; its components' crystal structures are available; and there are biochemical and cellular data. In the IFN-β enhanceosome, there are few protein-protein interactions even though consecutive DNA response elements (REs) overlap. Our molecular dynamics (MD) simulations on different motif combinations from the enhanceosome illustrate that cooperativity is achieved via unique organization of the REs: specific binding of one TF can enhance the binding of another TF to a neighboring RE and restrict others, through overlap of REs; the order of the REs can determine which complexes will form; and the alternation of consensus and non-consensus REs can regulate binding specificity by optimizing the interactions among partners. Our observations offer an explanation of how specificity and cooperativity can be attained despite the limited interactions between neighboring TFs on the enhancer DNA. To date, when addressing selective TF binding, attention has largely focused on RE sequences. Yet, the order of the REs on the DNA and the length of the spacers between them can be a key factor in specific combinatorial assembly of the TFs on the enhancer and thus in function. Our results emphasize cooperativity via RE binding sites organization

Prox1 Regulates the Notch1-Mediated Inhibition of Neurogenesis

During development of the spinal cord, Prox1 controls the balance between proliferation and differentiation of neural progenitor cells via suppression of Notch1 gene expression

Ca(BH4)2 + MgH2: Desorption Reaction and Role of Mg on Its Reversibility

The Ca(BH4)2–MgH2 composite system represents a promising candidate for mobile hydrogen storage due to a 10.5 wt % theoretical hydrogen storage capacity and an estimated equilibrium temperature lower than 160 °C. For this system, the reversibility was achieved without further addition of additives. In this study, the decomposition path of the Ca(BH4)2 + MgH2 composite system is investigated in detail by in situ synchrotron radiation powder X-ray diffraction and differential scanning calorimetry combined with thermogravimetry. The sorption properties are analyzed by volumetric measurements. 11B{1H} solid state magic angle spinning–nuclear magnetic resonance was employed for the characterization of the final amorphous or nanocrystalline boron-based decomposition products. This study shows that the intermediate formation of Ca4Mg3H14 upon dehydrogenation of the Ca(BH4)2–MgH2 composite system is not a necessary step, and its presence can be adjusted modifying the preparation procedure. Moreover, the d-value mismatch calculated for the {111}CaB6/{1011}Mg plane pair is the lowest among the other plane pairs considered in the system. The mismatch in the third direction between CaB6 and Mg is also extremely good. These findings propose Mg as a supporter of the heterogeneous nucleation of CaB6 during decomposition of the Ca(BH4)2 + MgH2 composite system

A hydride composite featuring mutual destabilisation and reversible boron exchange: Ca(BH4)2–Mg2NiH4Ca(BH_{4})_{2} –Mg_{2}NiH_{4}

The system $Ca(BH_{4})_{2} –Mg_{2}NiH_{4}$ is used as a model to prove the unique possibility to fully reverse the borohydride decomposition process even in cases where the decomposition reaction leads to undesired stable boron containing species (boron sinks). The formation of $MgNi_{2.5}B_2$ directly from $Ca(BH_4)_2$ or from $CaB_{12}H_{12}$ and amorphous boron allows an unexpectedly easy transfer of the boron atoms to reversibly form $Ca(BH_4)_2$ during rehydrogenation. In addition, to the best of our knowledge, the mutual destabilisation of the starting reactants is observed for the first time in $Ca(BH_4)_2$ based Reactive Hydride Composite (RHC) systems. A detailed account of dehydrogenation and rehydrogenation reaction mechanisms as the function of applied experimental conditions is given

Dissimilar catalytic behavior of molecular or colloidal palladium systems with a new NHC ligand

International audienceIn this work, we describe the synthesis of a new N-heterocyclic carbene (NHC) ligand, derived from a hybrid pyrazole-imidazolium scaffold, namely 1-[2-(3,5-dimethylpyrazol-1-yl)ethyl]-3-((S)-1-phenylethyl)-3H-imidazol-2-ylidene (L). This ligand has been used as a stabilizer for the organometallic synthesis of palladium(0) nanoparticles (Pd NPs). L presents a better stabilizing effect than its pre-carbenic HLCl counterpart, allowing the formation of isolated Pd NPs while HLCl yields aggregated ones. Additionally, molecular Pd(ii) coordination compounds of L and HLCl were synthesized and characterized to better understand the coordination modes of these ligands. Both molecular and colloidal Pd systems have been further tested in catalytic C-C coupling processes. Three different types of reactions have been observed depending on the catalytic system: (i) the Suzuki-Miyaura reaction takes place with Pd molecular complexes; (ii) a secondary reaction, the dehalogenation of the substrate, is always detected and (iii) the C-C homocoupling between two molecules of bromoarenes is observed with colloidal catalysts

Chemical State, Distribution, and Role of Ti- and Nb-Based Additives on the Ca(BH4)2 System

Light metal tetrahydroborates are regarded as promising materials for solid state hydrogen storage. Due to both a high gravimetric hydrogen capacity of 11.5 wt % and an ideal dehydrogenation enthalpy of 32 kJ mol–1 H2, Ca(BH4)2 is considered to be one of the most interesting compounds in this class of materials. In this work, a comprehensive investigation of the effect of different selected additives (TiF4, NbF5, Ti-isopropoxide, and CaF2) on the reversible hydrogenation reaction of calcium borohydride is presented combining different investigation techniques. The chemical state of the Nb- and Ti-based additives is studied by X-ray absorption spectroscopy (e.g., XANES). Transmission electron microscopy (TEM) coupled with selected area electron diffraction (SAED) and energy-dispersive X-ray spectroscopy (EDX) was used to show the local structure, size, and distribution of the additive/catalyst. 11B{1H} solid state magic angle spinning-nuclear magnetic resonance (MAS NMR) was carried out to detect possible amorphous phases. The formation of TiB2 and NbB2 nanoparticles was observed after milling or upon sorption reactions of the Nb- and Ti-based Ca(BH4)2 doped systems. The formation of transition-metal boride nanoparticles is proposed to support the heterogeneous nucleation of CaB6. The {111}CaB6/{1011}NbB2, {111}CaB6/{1010}NbB2, as well as {111}CaB6/{1011}TiB2 plane pairs have the potential to be the matching planes because the d-value mismatch is well below the d-critical mismatch value (6%). Transition-metal boride nanoparticles act as heterogeneous nucleation sites for CaB6, refine the microstructure thus improving the sorption kinetics, and, as a consequence, lead to the reversible formation of Ca(BH4)2

Effect of a partial replacement of CaH2 by CaF2 in the mixed system CaH2 + MgB2

In the last years, borohydrides have been extensively studied as possible candidates for hydrogen storage. Due to its high gravimetric and volumetric hydrogen capacity coupled with a calculated decomposition enthalpy in the range 30-40 kJ/mol H2, calcium borohydride represents an ideal candidate for storing hydrogen. Unfortunely, during to the formation of stable products during desorption, the pristine compound does not show a significant reversibility. A maximum reversibility of about 60 % was reported as possible only after addition of selected halogenated additives. It was shown that the complete formation of Ca(BH4)2 and MgH2 is possible by hydrogenation of the system CaH2 + MgB2. This system has still a high hydrogen gravimetric capacity, however the reversible hydrogenation of the system is still hindered by the formation of stable side products. In this work, the effect of a partial replacement of CaH2 by CaF2 on the sorption properties of the CaH2 + MgB2 system is studied. It was observed that already during the mixing of the reactants, the formation of a non stoichiometric CaH2-CaF2 solid solution takes place. The formation of this new phase affect sensibly the sorption reactions of the CaH2 + MgB2 system