The 21 cm Signature of Shock Heated and Diffuse Cosmic String Wakes

The analysis of the 21 cm signature of cosmic string wakes is extended in several ways. First we consider the constraints on $G\mu$ from the absorption signal of shock heated wakes laid down much later than matter radiation equality. Secondly we analyze the signal of diffuse wake, that is those wakes in which there is a baryon overdensity but which have not shock heated. Finally we compare the size of these signals compared to the expected thermal noise per pixel which dominates over the background cosmic gas brightness temperature and find that the cosmic string signal will exceed the thermal noise of an individual pixel in the Square Kilometre Array for string tensions $G\mu > 2.5 \times 10^{-8}$.Comment: 10 pages, 4 figures, Appendix added, version published in JCA

Structural mechanism for regulation of the AAA-ATPases RUVBL1-RUVBL2 in the R2TP co-chaperone revealed by cryo-EM

The human R2TP complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) is an HSP90 co-chaperone required for the maturation of several essential multiprotein complexes, including RNA polymerase II, small nucleolar ribonucleoproteins, and PIKK complexes such as mTORC1 and ATR-ATRIP. RUVBL1-RUVBL2 AAA-ATPases are also primary components of other essential complexes such as INO80 and Tip60 remodelers. Despite recent efforts, the molecular mechanisms regulating RUVBL1-RUVBL2 in these complexes remain elusive. Here, we report cryo-EM structures of R2TP and show how access to the nucleotide-binding site of RUVBL2 is coupled to binding of the client recruitment component of R2TP (PIH1D1) to its DII domain. This interaction induces conformational rearrangements that lead to the destabilization of an N-terminal segment of RUVBL2 that acts as a gatekeeper to nucleotide exchange. This mechanism couples protein-induced motions of the DII domains with accessibility of the nucleotide-binding site in RUVBL1-RUVBL2, and it is likely a general mechanism shared with other RUVBL1-RUVBL2-containing complexes

Broken SU(3) Symmetry in Two-Body B Decays

The decays of $B$ mesons to two-body hadronic final states are analyzed within the context of broken flavor SU(3) symmetry, extending a previous analysis involving pairs of light pseudoscalars to decays involving one or two charmed quarks in the final state. A systematic program is described for learning information {}from decay rates regarding (i) SU(3)-violating contributions, (ii) the magnitude of exchange and annihilation diagrams (effects involving the spectator quark), and (iii) strong final-state interactions. The implication of SU(3)-breaking effects for the extraction of weak phases is also examined. The present status of data on these questions is reviewed and suggestions for further experimental study are made.Comment: 38 pages, 8 figures, LaTeX file. The full postscript manuscript is available by anon ftp at ftp://lpsvsh.lps.umontreal.ca/theorie/hep-ph/SU3break.ps (a VAX so use the format theorie.hep-ph if you change by more than one directory at a time

The structure of the R2TP complex defines a platform for recruiting diverse client proteins to the HSP90 molecular chaperone system

The R2TP complex, comprising the Rvb1p-Rvb2p AAA-ATPases, Tah1p, and Pih1p in yeast, is a special- ized Hsp90 co-chaperone required for the assembly and maturation of multi-subunit complexes. These include the small nucleolar ribonucleoproteins, RNA polymerase II, and complexes containing phosphati- dylinositol-3-kinase-like kinases. The structure and stoichiometry of yeast R2TP and how it couples to Hsp90 are currently unknown. Here, we determine the 3D organization of yeast R2TP using sedimenta- tion velocity analysis and cryo-electron microscopy. The 359-kDa complex comprises one Rvb1p/Rvb2p hetero-hexamer with domains II (DIIs) forming an open basket that accommodates a single copy of Tah1p-Pih1p. Tah1p-Pih1p binding to multiple DII do- mains regulates Rvb1p/Rvb2p ATPase activity. Using domain dissection and cross-linking mass spectro- metry, we identified a unique region of Pih1p that is essential for interaction with Rvb1p/Rvb2p. These data provide a structural basis for understanding how R2TP couples an Hsp90 dimer to a diverse set of client proteins and complexes

RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex

The R2TP/Prefoldin-like co-chaperone, in concert with HSP90, facilitates assembly and cellular stability of RNA polymerase II, and complexes of PI3-kinase-like kinases such as mTOR. However, the mechanism by which this occurs is poorly understood. Here we use cryo-EM and biochemical studies on the human R2TP core (RUVBL1–RUVBL2–RPAP3–PIH1D1) which reveal the distinctive role of RPAP3, distinguishing metazoan R2TP from the smaller yeast equivalent. RPAP3 spans both faces of a single RUVBL ring, providing an extended scaffold that recruits clients and provides a flexible tether for HSP90. A 3.6 Å cryo-EM structure reveals direct interaction of a C-terminal domain of RPAP3 and the ATPase domain of RUVBL2, necessary for human R2TP assembly but absent from yeast. The mobile TPR domains of RPAP3 map to the opposite face of the ring, associating with PIH1D1, which mediates client protein recruitment. Thus, RPAP3 provides a flexible platform for bringing HSP90 into proximity with diverse client proteins