Evidence for additive and synergistic action of mammalian enhancers during cell fate determination

Enhancer activity drives cell differentiation and cell fate determination, but it remains unclear how enhancers cooperate during these processes. Here we investigate enhancer cooperation during transdifferentiation of human leukemia B-cells to macrophages. Putative enhancers are established by binding of the pioneer factor C/EBPα followed by chromatin opening and enhancer RNA (eRNA) synthesis from H3K4-monomethylated regions. Using eRNA synthesis as a proxy for enhancer activity, we find that most putative enhancers cooperate in an additive way to regulate transcription of assigned target genes. However, transcription from 136 target genes depends exponentially on the summed activity of its putative paired enhancers, indicating that these enhancers cooperate synergistically. The target genes are cell type-specific, suggesting that enhancer synergy can contribute to cell fate determination. Enhancer synergy appears to depend on cell type-specific transcription factors, and such interacting enhancers are not predicted from occupancy or accessibility data that are used to detect superenhancers

Radial and latitudinal dependencies of discontinuities in the solar wind between 0.3 and 19 AU and ?80° and +10°

International audienceDirectional discontinuities (DD) from 5 missions at 7 different locations between 0.3 and 19 AU and ?80° and +10° in the 3D heliosphere are investigated during minimum solar activity. The data are surveyed using the identification criteria of Burlaga (1969) (B) and Tsurutani and Smith (1979) (TS). The rate of occurrence depends linearly on the solar wind velocity caused by the geometric effect of investigating a larger plasma volume if the solar wind velocity ?sw increases. The radial dependence is proportional to r?0.78 (TS criterion) and r?1.28 (B criterion), respectively. This dependence is not only due to an increasing miss rate with increasing distance. The DDs must be unstable or some other physical effect must exist. After normalization of the daily rates to 400 km/s and 1 AU, no dependence on heliographic latitude or on solar wind structures is observable. This means that the DDs are uniformly distributed on a spherical shell. Normalized 64 DD per day are identified with both criteria. But large variations of the daily rate still occur, indicating that other influences must exist. The ratio of the rates of rotational (RDs) and tangential discontinuities (TDs) depends on the solar wind structures. In high speed streams, relatively more RDs exist than in low speed streams. In the inner heliosphere (r r ? over the transition evolves to an increase of smaller ? with increasing distance from the sun. The evolution is yielded by the anisotropic RDs with small ?. The spatial thickness dkm in kilometers increases with distance. The thickness drg normalized to the proton gyro radius decreases by a factor of 50 between 0.3 and 19 AU, from 201.3 rg down to 4.3 rg. In the middle heliosphere, the orientation of the normals relative to the local magnetic field is essentially uniform except for the parallel direction where no DDs occur. This indicates that RDs propagating parallel to B play a special role. In addition, in only a few cases is [?] parallel to [B / ?], which is required by the MHD theory for RDs. The DDs have strongly enhanced values of proton gyro radius rg for ? ~ 90°. In contrast, in the inner heliosphere, only a small increase in rg with ? is observed

Vortex lattices in a stirred Bose-Einstein condensate

We stir with a focused laser beam a Bose-Einstein condensate of $^{87}$Rb atoms confined in a magnetic trap. We observe the formation of a single vortex for a stirring frequency exceeding a critical value. At larger rotation frequencies we produce states of the condensate for which up to eleven vortices are simultaneously present. We present measurements of the decay of a vortex array once the stirring laser beam is removed

AbrB-like transcription factors assume a swapped hairpin fold that is evolutionarily related to double-psi beta barrels.

AbrB is a key transition-state regulator of Bacillus subtilis. Based on the conservation of a βαβ structural unit, we proposed a β barrel fold for its DNA binding domain, similar to, but topologically distinct from, double-psi β barrels. However, the NMR structure revealed a novel fold, the “looped-hinge helix.” To understand this discrepancy, we undertook a bioinformatics study of AbrB and its homologs; these form a large superfamily, which includes SpoVT, PrlF, MraZ, addiction module antidotes (PemI, MazE), plasmid maintenance proteins (VagC, VapB), and archaeal PhoU homologs. MazE and MraZ form swapped-hairpin β barrels. We therefore reexamined the fold of AbrB by NMR spectroscopy and found that it also forms a swapped-hairpin barrel. The conservation of the core βαβ element supports a common evolutionary origin for swapped-hairpin and double-psi barrels, which we group into a higher-order class, the cradle-loop barrels, based on the peculiar shape of their ligand binding site

Weakly bound atomic trimers in ultracold traps

The experimental three-atom recombination coefficients of the atomic states $^{23}$Na$|F=1,m_F=-1>$, $^{87}$Rb$|F=1,m_F=-1>$ and $^{85}$Rb$|F=2,m_F=-2>$, together with the corresponding two-body scattering lengths, allow predictions of the trimer bound state energies for such systems in a trap. The recombination parameter is given as a function of the weakly bound trimer energies, which are in the interval $1<m(a/\hbar)^2 E_3< 6.9$ for large positive scattering lengths, $a$. The contribution of a deep-bound state to our prediction, in the case of $^{85}$Rb$|F=2,m_F=-2>$, for a particular trap, is shown to be relatively small.Comment: 5 pages, 1 figur

Optimized production of a cesium Bose-Einstein condensate

We report on the optimized production of a Bose-Einstein condensate of cesium atoms using an optical trapping approach. Based on an improved trap loading and evaporation scheme we obtain more than $10^5$ atoms in the condensed phase. To test the tunability of the interaction in the condensate we study the expansion of the condensate as a function of scattering length. We further excite strong oscillations of the trapped condensate by rapidly varying the interaction strength.Comment: 9 pages, 7 figures, submitted to Appl. Phys.

Excitation-assisted inelastic processes in trapped Bose-Einstein condensates

We find that inelastic collisional processes in Bose-Einstein condensates induce local variations of the mean-field interparticle interaction and are accompanied by the creation/annihilation of elementary excitation. The physical picture is demonstrated for the case of three body recombination in a trapped condensate. For a high trap barrier the production of high energy trapped single particle excitations results in a strong increase of the loss rate of atoms from the condensate.Comment: 4 pages, no figure

Lysine/RNA-interactions drive and regulate biomolecular condensation.

Cells form and use biomolecular condensates to execute biochemical reactions. The molecular properties of non-membrane-bound condensates are directly connected to the amino acid content of disordered protein regions. Lysine plays an important role in cellular function, but little is known about its role in biomolecular condensation. Here we show that protein disorder is abundant in protein/RNA granules and lysine is enriched in disordered regions of proteins in P-bodies compared to the entire human disordered proteome. Lysine-rich polypeptides phase separate into lysine/RNA-coacervates that are more dynamic and differ at the molecular level from arginine/RNA-coacervates. Consistent with the ability of lysine to drive phase separation, lysine-rich variants of the Alzheimer's disease-linked protein tau undergo coacervation with RNA in vitro and bind to stress granules in cells. Acetylation of lysine reverses liquid-liquid phase separation and reduces colocalization of tau with stress granules. Our study establishes lysine as an important regulator of cellular condensation

Phase-fluctuating 3D condensates in elongated traps

We find that in very elongated 3D trapped Bose gases, even at temperatures far below the BEC transition temperature Tc, the equilibrium state will be a 3D condensate with fluctuating phase (quasicondensate). At sufficiently low temperatures the phase fluctuations are suppressed and the quasicondensate turns into a true condensate. The presence of the phase fluctuations allows for extending thermometry of Bose-condensed gases well below those established in current experiments.Comment: 5 pages REVTeX, 3 figures, misprints correcte

Involvement of a Natural Fusion of a Cytochrome P450 and a Hydrolase in Mycophenolic Acid Biosynthesis

Mycophenolic acid (MPA) is a fungal secondary metabolite and the active component in several immunosuppressive pharmaceuticals. The gene cluster coding for the MPA biosynthetic pathway has recently been discovered in Penicillium brevicompactum, demonstrating that the first step is catalyzed by MpaC, a polyketide synthase producing 5-methylorsellinic acid (5-MOA). However, the biochemical role of the enzymes encoded by the remaining genes in the MPA gene cluster is still unknown. Based on bioinformatic analysis of the MPA gene cluster, we hypothesized that the step following 5-MOA production in the pathway is carried out by a natural fusion enzyme MpaDE, consisting of a cytochrome P450 (MpaD) in the N-terminal region and a hydrolase (MpaE) in the C-terminal region. We verified that the fusion gene is indeed expressed in P. brevicompactum by obtaining full-length sequence of the mpaDE cDNA prepared from the extracted RNA. Heterologous coexpression of mpaC and the fusion gene mpaDE in the MPA-nonproducer Aspergillus nidulans resulted in the production of 5,7-dihydroxy-4-methylphthalide (DHMP), the second intermediate in MPA biosynthesis. Analysis of the strain coexpressing mpaC and the mpaD part of mpaDE shows that the P450 catalyzes hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB). DHMB is then converted to DHMP, and our results suggest that the hydrolase domain aids this second step by acting as a lactone synthase that catalyzes the ring closure. Overall, the chimeric enzyme MpaDE provides insight into the genetic organization of the MPA biosynthesis pathway