Sticky swinging arm dynamics: studies of an acyl carrier protein domain from the mycolactone polyketide synthase.

Type I modular polyketide synthases (PKSs) produce polyketide natural products by passing a growing acyl substrate chain between a series of enzyme domains housed within a gigantic multifunctional polypeptide assembly. Throughout each round of chain extension and modification reactions, the substrate stays covalently linked to an acyl carrier protein (ACP) domain. In the present study we report on the solution structure and dynamics of an ACP domain excised from MLSA2, module 9 of the PKS system that constructs the macrolactone ring of the toxin mycolactone, cause of the tropical disease Buruli ulcer. After modification of apo ACP with 4'-phosphopantetheine (Ppant) to create the holo form, (15)N nuclear spin relaxation and paramagnetic relaxation enhancement (PRE) experiments suggest that the prosthetic group swings freely. The minimal chemical shift perturbations displayed by Ppant-attached C3 and C4 acyl chains imply that these substrate-mimics remain exposed to solvent at the end of a flexible Ppant arm. By contrast, hexanoyl and octanoyl chains yield much larger chemical shift perturbations, indicating that they interact with the surface of the domain. The solution structure of octanoyl-ACP shows the Ppant arm bending to allow the acyl chain to nestle into a nonpolar pocket, whereas the prosthetic group itself remains largely solvent exposed. Although the highly reduced octanoyl group is not a natural substrate for the ACP from MLSA2, similar presentation modes would permit partner enzyme domains to recognize an acyl group while it is bound to the surface of its carrier protein, allowing simultaneous interactions with both the substrate and the ACP.This work was supported by the Wellcome Trust [grant number 094252/Z/10/Z]. The Yousef Jameel Academic Foundation and the Cambridge Trust are thanked for providing a studentship to M.B.This is the final version of the article. It first appeared from Portland Press via https://doi.org/10.1042/BCJ2016004

QCD Sum Rules for Masses of Excited Heavy Mesons

The masses of excited heavy mesons are studied with sum rules in the heavy quark effective theory. A set of interpolating currents creating (annihilating) excited heavy mesons with arbitrary spin and parity are proposed and their properties are discussed. Numerical results at the leading order of the {\cal O}(1/m_Q) expansion are obtained for the lowest doublets (0^+, 1^+) and (1^+, 2^+).Comment: LateX, 12 pages including 2 fig

Understanding the DsJ+(2317)D^+_{sJ}(2317) and DsJ+(2460)D^+_{sJ}(2460) with Sum Rules in HQET

In the framework of heavy quark effective theory we use QCD sum rules to calculate the masses of the $\bar c s$ $(0^+, 1^+)$ and $(1^+, 2^+)$ excited states. The results are consistent with that the states $D_{sJ}(2317)$ and $D_{sJ}(2460)$ observed by BABAR and CLEO are the $0^+$ and $1^+$ states in the $j_l={1\over 2}^+$ doublet

Semileptonic B decays into excited charmed mesons from QCD sum rules

Exclusive semileptonic $B$ decays into excited charmed mesons are studied with QCD sum rules in the leading order of heavy quark effective theory. Two universal Isgur-Wise functions \tau and \zeta for semileptonic B decays into four lowest lying excited $D$ mesons ($D_1$, $D_2^*$, $D'_0$, and $D'_1$) are determined. The decay rates and branching ratios for these processes are calculated.Comment: RevTeX, 17 pages including 2 figure

Analysis of the natively unstructured RNA/protein-recognition core in the Escherichia coli RNA degradosome and its interactions with regulatory RNA/Hfq complexes.

The RNA degradosome is a multi-enzyme assembly that plays a central role in the RNA metabolism of Escherichia coli and numerous other bacterial species including pathogens. At the core of the assembly is the endoribonuclease RNase E, one of the largest E. coli proteins and also one that bears the greatest region predicted to be natively unstructured. This extensive unstructured region, situated in the C-terminal half of RNase E, is punctuated with conserved short linear motifs that recruit partner proteins, direct RNA interactions, and enable association with the cytoplasmic membrane. We have structurally characterized a subassembly of the degradosome-comprising a 248-residue segment of the natively unstructured part of RNase E, the DEAD-box helicase RhlB and the glycolytic enzyme enolase, and provide evidence that it serves as a flexible recognition centre that can co-recruit small regulatory RNA and the RNA chaperone Hfq. Our results support a model in which the degradosome captures substrates and regulatory RNAs through the recognition centre, facilitates pairing to cognate transcripts and presents the target to the ribonuclease active sites of the greater assembly for cooperative degradation or processing

The masses and decay widths of heavy hybrid mesons

We first derive the mass sum rules for the heavy hybrid mesons to obtain the binding energy and decay constants in the leading order of HQET. The pionic couplings between the lightest $1^{-+}$ hybrid $(Q\bar q g)$ and the lowest three heavy meson doublets are calculated with the light cone QCD sum rules. With $SU_f (3)$ flavor symmetry we calculate the widths for all the possible two-body decay processes with a Goldstone boson in the final state. The total width of the $1^{-+}$ hybrid is estimated to be 300 MeV. We find the dominant decay mode of the $1^{-+}$ hybrid is $1^{-+}\to \pi + 1^+$ where the $1^+$ heavy meson belongs to the $(1^+,2^+)$ doublet. Its branching ratio is about 80% so this mode can be used for the experimental search of the lowest heavy hybrid meson.Comment: 20 pages + 12 PS figures, introduction revised, Fig 7 updated, to appear in Phys. Rev.

Maternal positions and mobility during first stage labour

Background: It is more common for women in both high- and low-income countries giving birth in health facilities, to labour in bed. There is no evidence that this is associated with any advantage for women or babies, although it may be more convenient for staff. Observational studies have suggested that if women lie on their backs during labour this may have adverse effects on uterine contractions and impede progress in labour, and in some women reduce placental blood flow. Objectives: To assess the effects of encouraging women to assume different upright positions (including walking, sitting, standing and kneeling) versus recumbent positions (supine, semi-recumbent and lateral) for women in the first stage of labour on duration of labour, type of birth and other important outcomes for mothers and babies. Search methods: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 January 2013). Selection criteria Randomised and quasi-randomised trials comparing women randomised to upright versus recumbent positions in the first stage of labour. Data collection and analysis: We used methods described in the Cochrane Handbook for Systematic Reviews of Interventions for carrying out data collection, assessing study quality and analysing results. Two review authors independently evaluated methodological quality and extracted data for each study. We sought additional information from trial authors as required. We used random-effects analysis for comparisons in which high heterogeneity was present. We reported results using the average risk ratio (RR) for categorical data and mean difference (MD) for continuous data. Main results: Results should be interpreted with caution as the methodological quality of the 25 included trials (5218 women) was variable. For Comparison 1: Upright and recumbent positions versus recumbent positions and bed care, the first stage of labour was approximately one hour and 22 minutes shorter for women randomised to upright as opposed to recumbent positions (average MD -1.36, 95% confidence interval (CI) -2.22 to -0.51; 15 studies, 2503 women; random-effects, T2 = 2.39, Chi2 = 203.55, df = 14, (P < 0.00001), I2 = 93%). Women who were upright were also less likely to have caesarean section (RR 0.71, 95% CI 0.54 to 0.94; 14 studies, 2682 women) and less likely to have an epidural (RR 0.81, 95% CI 0.66 to 0.99, nine studies, 2107 women; random-effects, T2 = 0.02, I2 = 61%). Babies of mothers who were upright were less likely to be admitted to the neonatal intensive care unit, however this was based on one trial (RR 0.20, 95% CI 0.04 to 0.89, one study, 200 women). There were no significant differences between groups for other outcomes including duration of the second stage of labour, or other outcomes related to the well being of mothers and babies. For Comparison 2: Upright and recumbent positions versus recumbent positions and bed care (with epidural: all women), there were no significant differences between groups for outcomes including duration of the second stage of labour, or other outcomes related to the well being of mothers and babies. Authors' conclusions: There is clear and important evidence that walking and upright positions in the first stage of labour reduces the duration of labour, the risk of caesarean birth, the need for epidural, and does not seem to be associated with increased intervention or negative effects on mothers' and babies' well being. Given the great heterogeneity and high performance bias of study situations, better quality trials are still required to confirm with any confidence the true risks and benefits of upright and mobile positions compared with recumbent positions for all women. Based on the current findings, we recommend that women in low-risk labour should be informed of the benefits of upright positions, and encouraged and assisted to assume whatever positions they choose