Urease is an essential component of the acid response network of \u3ci\u3eStaphylococcus\u3c/i\u3e aureus and is required for a persistent murine kidney infection

Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic flux. In addition, it was determined that the endogenous urea derived from arginine is not a significant contributor to the intracellular nitrogen pool in non-acidic conditions. Furthermore, we found that during a murine chronic renal infection, urease facilitates S. aureus persistence by promoting bacterial fitness in the low-pH, urea-rich kidney. Overall, our study establishes that urease in S. aureus is not only a primary component of the acid response network but also an important factor required for persistent murine renal infections

Urease is an Essential Component of the Acid Response Network of Staphylococcus Aureus and is Required for a Persistent Murine Kidney Infection

Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic flux. In addition, it was determined that the endogenous urea derived from arginine is not a significant contributor to the intracellular nitrogen pool in non-acidic conditions. Furthermore, we found that during a murine chronic renal infection, urease facilitates S. aureus persistence by promoting bacterial fitness in the low-pH, urea-rich kidney. Overall, our study establishes that urease in S. aureus is not only a primary component of the acid response network but also an important factor required for persistent murine renal infections

Modified chitosan for effective renal delivery of siRNA to treat acute kidney injury.

Acute kidney injury (AKI) is characterized by a sudden decrease in renal function and impacts growing number of people worldwide. RNA interference (RNAi) showed potential to treat diseases with no or limited conventional therapies, including AKI. Suitable carriers are needed to protect and selectively deliver RNAi to target cells to fully explore this therapeutic modality. Here, we report on the synthesis of chitosan modified with α-cyclam-p-toluic acid (C-CS) as a novel siRNA carrier for targeted delivery to injured kidneys. We demonstrate that conjugation of the α-cyclam-p-toluic acid to chitosan imparts the C-CS polymer with targeting and antagonistic properties to cells overexpressing chemokine receptor CXCR4. In contrast, the parent α-cyclam-p-toluic acid showed no such properties. Self-assembled C-CS/siRNA nanoparticles rapidly accumulate in the injured kidneys and show long retention in renal tubules. Apoptosis and metabolic and inflammatory pathways induced by p53 are important pathological mechanisms in the development of AKI. Nanoparticles with siRNA against p53 (sip53) were formulated and intravenously injected for attenuation of IRI-AKI. Due to the favorable accumulation in injured kidneys, the treatment with C-CS/sip53 decreased renal injury, extent of renal apoptosis, macrophage and neutrophil infiltration, and improved renal function. Overall, our study suggests that C-CS/siRNA nanoparticles have the potential to effectively accumulate and deliver therapeutic siRNAs to injured kidneys through CXCR4 binding, providing a novel way for AKI therapy

Dense Cores in Perseus: The Influence of Stellar Content and Cluster Environment

We present the chemistry, temperature, and dynamical state of a sample of 193 dense cores or core candidates in the Perseus Molecular cloud and compare the properties of cores associated with young stars and clusters with those which are not. The combination of our NH3 and CCS observations with previous millimeter, sub-millimeter, and Spitzer data available for this cloud enable us both to determine core properties precisely and to accurately classify cores as starless or protostellar. The properties of cores in different cluster environments and before-and-after star formation provide important constraints on simulations of star-formation, particularly under the paradigm that the essence of star formation is set by the turbulent formation of prestellar cores. We separate the influence of stellar content from that of cluster environment and find that cores within clusters have (1) higher kinetic temperatures and (2) lower fractional abundances of CCS and NH3. Cores associated with protostars have (1) slightly higher kinetic temperatures (2) higher NH3 excitation temperatures), (3) are at higher column density, have (4) slightly more non-thermal/turbulent NH3 linewidths, have (5) higher masses and have (6) lower fractional abundance of CCS. We find that neither cluster environment nor protostellar content makes a significant difference to the dynamical state of cores as estimated by the virial parameter -- most cores in each category are gravitationally bound. Overall, cluster environment and protostellar content have a smaller influence on the properties of the cores than is typically assumed, and the variation within categories is larger than the differences between categories.Comment: 28 pages, 17 figures. Accepted to Ap

Comparing the statistics of interstellar turbulence in simulations and observations: Solenoidal versus compressive turbulence forcing

We study two limiting cases of turbulence forcing in numerical experiments: solenoidal (divergence-free) forcing, and compressive (curl-free) forcing, and compare our results to observations reported in the literature. We solve the equations of hydrodynamics on grids with up to 1024^3 cells for purely solenoidal and purely compressive forcing. Eleven lower-resolution models with mixtures of both forcings are also analysed. We find velocity dispersion--size relations consistent with observations and independent numerical simulations, irrespective of the type of forcing. However, compressive forcing yields stronger turbulent compression at the same RMS Mach number than solenoidal forcing, resulting in a three times larger standard deviation of volumetric and column density probability distributions (PDFs). We conclude that the strong dependence of the density PDF on the type of forcing must be taken into account in any theory using the PDF to predict properties of star formation. We supply a quantitative description of this dependence. We find that different observed regions show evidence of different mixtures of compressive and solenoidal forcing, with more compressive forcing occurring primarily in swept-up shells.Comment: 28 pages, 20 figures, published as Highlight Paper in A&A, 512, A81 (2010); simulation movies available at http://www.ita.uni-heidelberg.de/~chfeder/videos.shtml?lang=e

Measurement of the Strong Coupling Constant from Inclusive Jet Production at the Tevatron pˉp\bar pp Collider

We report a measurement of the strong coupling constant, $\alpha_s(M_Z)$, extracted from inclusive jet production in $p\bar{p}$ collisions at $\sqrt{s}=$1800 GeV. The QCD prediction for the evolution of $\alpha_s$ with jet transverse energy $E_T$ is tested over the range 40<$E_T$<450 GeV using $E_T$ for the renormalization scale. The data show good agreement with QCD in the region below 250 GeV. In the text we discuss the data-theory comparison in the region from 250 to 450 GeV. The value of $\alpha_s$ at the mass of the $Z^0$ boson averaged over the range 40<$E_T$<250 GeV is found to be $\alpha_s(M_{Z})= 0.1178 \pm 0.0001{(\rm stat)}^{+0.0081}_{-0.0095}{\rm (exp. syst)}$. The associated theoretical uncertainties are mainly due to the choice of renormalization scale (^{+6%}_{-4%}) and input parton distribution functions (5%).Comment: 7 pages, 3 figures, using RevTeX. Submitted to Physical Review Letter

Measurement of Rapidity Distribution for High Mass Drell-Yan ee Pairs at CDF

We report on the first measurement of the rapidity distribution dsigma/dy over nearly the entire kinematic region of rapidity for e^+e^- pairs in the Z-boson region of 66116 GeV/c^2. The data sample consists of 108 pb^{-1} of ppbar collisions at \sqrt{s}=1.8 TeV taken by the Collider Detector at Fermilab during 1992--1995. The total cross section in the $Z$-boson region is measured to be 252 +- 11 pb. The measured total cross section and d\sigma/dy are compared with quantum chromodynamics calculations in leading and higher orders.Comment: 7 pages, 3 figures. Submitted to Physical Review Letter

Search for a Fourth-Generation Quark More Massive than the Z0 Boson in ppbar Collisions at sqrt(s) = 1.8 TeV

We present the results of a search for pair production of a fourth-generation charge -1/3 quark (b') in sqrt(s)=1.8 TeV ppbar collisions using 88 pb^(-1) of data obtained with the Collider Detector at Fermilab. We assume that both quarks decay via the flavor-changing neutral current process b' -> bZ and that the b' mass is greater than m_Z + m_b. We studied the decay mode b'b'bar -> ZZ b bbar where one Z0 decays into e^+e^- or mu^+ mu^- and the other decays hadronically, giving a signature of two leptons plus jets. An upper limit on the cross section of ppbar -> b'b'bar times [BR (b' -> bZ)]^2 is established as a function of the b' mass. We exclude at 95% confidence level a b' quark with mass between 100 and 199 GeV/c^2 for BR(b' -> bZ) = 100%.Comment: 12 pages, 2 figures, submitted to Phys. Rev. Letters on 9/12/9

Search for the Supersymmetric Partner of the Top-Quark in ppˉp \bar{p} Collisions at s=1.8TeV\sqrt{s} = 1.8 {\rm TeV}

We report on a search for the supersymmetric partner of the top quark (stop) produced in $t \bar{t}$ events using $110 {\rm pb}^{-1}$ of $p \bar{p}$ collisions at $\sqrt{s} = 1.8 {\rm TeV}$ recorded with the Collider Detector at Fermilab. In the case of a light stop squark, the decay of the top quark into stop plus the lightest supersymmetric particle (LSP) could have a significant branching ratio. The observed events are consistent with Standard Model $t \bar{t}$ production and decay. Hence, we set limits on the branching ratio of the top quark decaying into stop plus LSP, excluding branching ratios above 45% for a LSP mass up to 40 {\rm GeV/c}$^{2}$.Comment: 11 pages, 4 figure

Measurement of the ttˉproductioncrosssectionint\bar{t} production cross section in p\bar{p}collisionsat collisions at \sqrt{s}$ = 1.8 TeV

We update the measurement of the top production cross section using the CDF detector at the Fermilab Tevatron. This measurement uses $t\bar{t}$ decays to the final states $e+\nu$+jets and $\mu+\nu$+jets. We search for $b$ quarks from $t$ decays via secondary-vertex identification or the identification of semileptonic decays of the $b$ and cascade $c$ quarks. The background to the $t\bar{t}$ production is determined primarily through a Monte Carlo simulation. However, we calibrate the simulation and evaluate its uncertainty using several independent data samples. For a top mass of 175 $GeV/c^2$, we measure $\sigma_{t\bar{t}}=5.1 \pm 1.5$ pb and $\sigma_{t\bar{t}}=9.2 \pm 4.3$ pb using the secondary vertex and the lepton tagging algorithms, respectively. Finally, we combine these results with those from other $t\bar{t}$ decay channels and obtain $\sigma_{t\bar{t}} = 6.5^{+1.7}_{-1.4}$ pb.Comment: The manuscript consists of 130 pages, 35 figures and 42 tables in RevTex. The manuscript is submitted to Physical Review D. Fixed typo in author lis