Analysis of Six tonB Gene Homologs in Bacteroides Fragilis Revealed That tonB3 is Essential for Survival in Experimental Intestinal Colonization and Intra-Abdominal Infection

The opportunistic, anaerobic pathogen and commensal of the human large intestinal tract, Bacteroides fragilis strain 638R, contains six predicted TonB proteins, termed TonB1-6, four ExbBs orthologs, ExbB1-4, and five ExbDs orthologs, ExbD1-5. The inner membrane TonB/ExbB/ExbD complex harvests energy from the proton motive force (Δp), and the TonB C-terminal domain interacts with and transduces energy to outer membrane TonB-dependent transporters (TBDTs). However, TonB’s role in activating nearly one hundred TBDTs for nutrient acquisition in B. fragilis during intestinal colonization and extraintestinal infection has not been established. In this study, we show that growth was abolished in the ΔtonB3 mutant when heme, vitamin B(12), Fe(III)-ferrichrome, starch, mucin-glycans, or N-linked glycans were used as a substrate for growth in vitro. Genetic complementation of the ΔtonB3 mutant with the tonB3 gene restored growth on these substrates. The ΔtonB1, ΔtonB2, ΔtonB4, ΔtonB5, and ΔtonB6 single mutants did not show a growth defect. This indicates that there was no functional compensation for the lack of TonB3, and it demonstrates that TonB3, alone, drives the TBDTs involved in the transport of essential nutrients. The ΔtonB3 mutant had a severe growth defect in a mouse model of intestinal colonization compared to the parent strain. This intestinal growth defect was enhanced in the ΔtonB3 ΔtonB6 double mutant strain, which completely lost its ability to colonize the mouse intestinal tract compared to the parent strain. The ΔtonB1, ΔtonB2, ΔtonB4, and ΔtonB5 mutants did not significantly affect intestinal colonization. Moreover, the survival of the ΔtonB3 mutant strain was completely eradicated in a rat model of intra-abdominal infection. Taken together, these findings show that TonB3 was essential for survival in vivo. The genetic organization of tonB1, tonB2, tonB4, tonB5, and tonB6 gene orthologs indicates that they may interact with periplasmic and nonreceptor outer membrane proteins, but the physiological relevance of this has not been defined. Because anaerobic fermentation metabolism yields a lower Δp than aerobic respiration and B. fragilis has a reduced redox state in its periplasmic space—in contrast to an oxidative environment in aerobes—it remains to be determined if the diverse system of TonB/ExbB/ExbD orthologs encoded by B. fragilis have an increased sensitivity to PMF (relative to aerobic bacteria) to allow for the harvesting of energy under anaerobic conditions

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

We tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD (+) intermediate, increases arterial SIRT1 activity and reverses age‐associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid artery endothelium‐dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)‐mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age‐associated impairment in EDD was restored in OC by the superoxide ([Formula: see text]) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s(−1) vs. 337 ± 3 cm s(−1)) and elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large elastic artery stiffness, compared with YC. OC had greater aortic [Formula: see text] production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen‐I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO‐mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s(−1)) and EM (3694 ± 315 kPa), normalized [Formula: see text] production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen‐I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD (+) threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age‐related arterial dysfunction by decreasing oxidative stress

Energy dependence of elliptic flow over a large pseudorapidity range in Au+Au collisions at RHIC

This paper describes the measurement of the energy dependence of elliptic flow for charged particles in Au+Au collisions using the PHOBOS detector at the Relativistic Heavy Ion Collider (RHIC). Data taken at collision energies of $\sqrt{s_{_{NN}}} =$ 19.6, 62.4, 130 and 200 GeV are shown over a wide range in pseudorapidity. These results, when plotted as a function of $\eta'=|\eta|-y_{beam}$, scale with approximate linearity throughout $\eta'$, implying no sharp changes in the dynamics of particle production as a function of pseudorapidity or increasing beam energy.Comment: 5 pages, 4 figure

Transverse Momentum and Rapidity Dependence of HBT Correlations in Au+Au Collisions at sqrt(s_NN) = 62.4 and 200 GeV

Two-particle correlations of identical charged pion pairs from Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV were measured by the PHOBOS experiment at RHIC. Data for the 15% most central events were analyzed with Bertsch-Pratt and Yano-Koonin-Podgoretskii parameterizations using pairs with rapidities of 0.4 < y_{\pi\pi} < 1.3 and transverse momenta 0.1 < k_T < 1.4 GeV/c. The Bertsch-Pratt radii R_o and R_l decrease as a function of pair transverse momentum, while R_s is consistent with a weaker dependence. R_o and R_s are independent of collision energy, while R_l shows a slight increase. The source rapidity y_{ykp} scales roughly with the pair rapidity y_{\pi\pi}, indicating strong dynamical correlations.Comment: 5 pages, 4 figures, 2 tables, submitted to Phys. Rev.

Forward-Backward Multiplicity Correlations in sqrt(s_NN) = 200 GeV Gold-Gold Collisions

Forward-backward correlations of charged-particle multiplicities in symmetric bins in pseudorapidity are studied in order to gain insight into the underlying correlation structure of particle production in Au+Au collisions. The PHOBOS detector is used to measure integrated multiplicities in bins centered at eta, defined within |eta|<3, and covering intervals Delta-eta. The variance sigma^2_C of a suitably defined forward-backward asymmetry variable C is calculated as a function of eta, Delta-eta, and centrality. It is found to be sensitive to short range correlations, and the concept of "clustering'' is used to interpret comparisons to phenomenological models.Comment: 5 Pages, 5 Figures, submitted to Physical Review C -- Rapid Communication

Event-by-event fluctuations of azimuthal particle anisotropy in Au+Au collisions at sqrt(s_NN) = 200 GeV

This paper presents the first measurement of event-by-event fluctuations of the elliptic flow parameter v_2 in Au+Au collisions at sqrt(s_NN) = 200GeV as a function of collision centrality. The relative non-statistical fluctuations of the v_2 parameter are found to be approximately 40%. The results, including contributions from event-by-event elliptic flow fluctuations and from azimuthal correlations that are unrelated to the reaction plane (non-flow correlations), establish an upper limit on the magnitude of underlying elliptic flow fluctuations. This limit is consistent with predictions based on spatial fluctuations of the participating nucleons in the initial nuclear overlap region. These results provide important constraints on models of the initial state and hydrodynamic evolution of relativistic heavy ion collisions.Comment: 5 pages, 2 figures, Published in Phys. Rev. Lett

Non-flow correlations and elliptic flow fluctuations in gold-gold collisions at sqrt(s_NN)= 200 GeV

This paper presents results on event-by-event elliptic flow fluctuations in Au+Au collisions at sqrt(s_NN)=200Gev, where the contribution from non-flow correlations has been subtracted. An analysis method is introduced to measure non-flow correlations, relying on the assumption that non-flow correlations are most prominent at short ranges (Delta eta < 2). Assuming that non-flow correlations are of the order that is observed in p+p collisions for long range correlations (Delta eta > 2), relative elliptic flow fluctuations of approximately 30-40% are observed. These results are consistent with predictions based on spatial fluctuations of the participating nucleons in the initial nuclear overlap region. It is found that the long range non-flow correlations in Au+Au collisions would have to be more than an order of magnitude stronger compared to the p+p data to lead to the observed azimuthal anisotropy fluctuations with no intrinsic elliptic flow fluctuations.Comment: 9 pages, 7 figures, Published in Phys. Rev.

Charged-Particle Pseudorapidity Distributions in Au+Au Collisions at sqrt(s_NN)=62.4 GeV

The charged-particle pseudorapidity density for Au+Au collisions at sqrt(s_NN)=62.4 GeV has been measured over a wide range of impact parameters and compared to results obtained at other energies. As a function of collision energy, the pseudorapidity distribution grows systematically both in height and width. The mid-rapidity density is found to grow approximately logarithmically between AGS energies and the top RHIC energy. As a function of centrality, there is an approximate factorization of the centrality dependence of the mid-rapidity yields and the overall multiplicity scale. The new results at sqrt(s_NN)=62.4 GeV confirm the previously observed phenomenon of ``extended longitudinal scaling'' in the pseudorapidity distributions when viewed in the rest frame of one of the colliding nuclei. It is also found that the evolution of the shape of the distribution with centrality is energy independent, when viewed in this reference frame. As a function of centrality, the total charged particle multiplicity scales linearly with the number of participant pairs as it was observed at other energies.Comment: 6 pages, 7 figures, submitted to Phys. Rev. C - Rapid Communication

System Size, Energy, Pseudorapidity, and Centrality Dependence of Elliptic Flow

This paper presents measurements of the elliptic flow of charged particles as a function of pseudorapidity and centrality from Cu-Cu collisions at 62.4 and 200 GeV using the PHOBOS detector at the Relativistic Heavy Ion Collider (RHIC). The elliptic flow in Cu-Cu collisions is found to be significant even for the most central events. For comparison with the Au-Au results, it is found that the detailed way in which the collision geometry (eccentricity) is estimated is of critical importance when scaling out system-size effects. A new form of eccentricity, called the participant eccentricity, is introduced which yields a scaled elliptic flow in the Cu-Cu system that has the same relative magnitude and qualitative features as that in the Au-Au system

Latest Results from PHOBOS

This manuscript contains a summary of the latest physics results from PHOBOS, as reported at Quark Matter 2006. Highlights include the first measurement from PHOBOS of dynamical elliptic flow fluctuations as well as an explanation of their possible origin, two-particle correlations, identified particle ratios, identified particle spectra and the latest results in global charged particle production.Comment: 9 pages, 7 figures, PHOBOS plenary proceedings for Quark Matter 200