The enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) is responsible for the formation of mannose 1-phosphate and glucose 1-phosphate in the human pathogenic bacterium Pseudomonas aeruginosa. ...Mannose 1-phosphate and glucose 1-phosphate are required for the biosynthesis of polysaccharides that contribute to the virulence of P. aeruginosa, so inhibitors of PMM/PGM may lead to clinically useful compounds. The V/K values for mannose 6-phosphate and glucose 6-phosphate show that they are equally good substrates for the enzyme. PMM/PGM overexpressed in Escherichia coli is isolated as a phosphoenzyme; surprisingly, mutation of serine 108 where phosphorylation occurs results in phosphorylation of a different residue so that activity is reduced only 20-fold from that of wild-type enzyme. In the reverse reaction glucose 1-phosphate exhibits substrate inhibition, which arises through its competition with the activator glucose 1,6-bisphosphate for binding to dephosphoenzyme. This phenomenon is consistent with a mechanism in which the enzyme phosphorylates the substrate to generate a bisphosphorylated intermediate that reorients in the active site to return its original phosphoryl group to the enzyme and generate the observed product. The pH dependence of the kinetic parameters suggests that the active site contains a residue that serves as a general base in the catalytic reaction and one that acts as a general acid. However, the pK of the general acid is 7.4 and that of the general base is 8.4 so these residues exist in a state of reverse protonation in the active enzyme.
Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are complex psychiatric conditions that commonly co-occur. No preferred, evidence-based treatments for PTSD/SUD comorbidity are ...presently available. Promising integrated treatments have combined prolonged exposure therapy with cognitive-behavioral relapse prevention therapy for SUD. We describe a case study that showcases a novel, integrated cognitive-behavioral treatment approach for PTSD/SUD, entitled Treatment of Integrated Posttraumatic Stress and Substance Use (TIPSS). The TIPSS program integrates cognitive processing therapy with cognitive-behavioral therapy for SUD for the treatment of co-occurring PTSD/SUD. The present case report, based upon a woman with PTSD comorbid with both cocaine and alcohol dependence, demonstrates that TIPSS has the potential to effectively reduce PTSD symptoms as well as substance use.
•This case study showcases a novel, integrated cognitive-behavioral treatment approach for posttraumatic stress and substance use disorders.•Novel approach is entitled Treatment of Integrated Posttraumatic Stress and Substance Use (TIPSS).•TIPSS integrates cognitive processing therapy with cognitive-behavioral therapy for substance use disorder.•The treatment is comprised of 12, 60-minute individual psychotherapy sessions.•The profiled case demonstrates significant reduction in PTSD symptoms and substance use.
The enzyme RhlI catalyzes the formation of N-butyrylhomoserine lactone from S-adenosylmethionine and N-butyrylacyl carrier protein. N-Butyrylhomoserine lactone serves as a quorum-sensing signal ...molecule in Pseudomonas aeruginosa, and is implicated in the regulation of many processes involved in bacterial virulence and infectivity. The P. aeruginosa genome contains three genes encoding acyl carrier proteins. We have cloned all three genes, expressed the acyl carrier proteins, and characterized each as a substrate for RhlI. A continuous, spectrophotometric assay was developed to facilitate kinetic and mechanistic studies of RhlI. Acp1, which has not been characterized previously, was a good substrate for RhlI, with a K m of 7 μM; the reaction proceeded with a k cat value of 0.35 s-1. AcpP, which supports fatty acid biosynthesis, was also a good substrate in the RhlI reaction, where k cat was 0.46 s-1, and the K m for AcpP was 6 μM. The third acyl carrier protein, Acp3, was a poor substrate for RhlI, with a K m of 280 μM; k cat was 0.03 s-1. Taken together with microarray data from the literature which show that expression of the gene encoding Acp1 is under the control of the quorum-sensing system, our data suggest that Acp1 is likely to be the substrate for RhlI in vivo. Isotope labeling studies were conducted to investigate the chemical mechanism of the RhlI-catalyzed lactonization reaction. Solvent deuterons were not incorporated into product, which implicates a direct attack mechanism in which the carboxylate oxygen of the presumptive N-butyryl-SAM intermediate attacks the methylene carbon adjacent to the sulfonium ion. Alternative mechanisms, in which N-butyrylvinylglycine is formed via elimination of methylthioadenosine, were ruled out on the basis of the observation that RhlI failed to convert authentic N-butyrylvinylglycine to N-butyryl-l-homoserine lactone.
A new generation of higher gain commercial buck converters built using advanced short channel CMOS processes has the potential to operate in the Atlas Inner Detector at the Super Large Hadron ...Collider (sLHC). This approach would inherently be more efficient than the existing practice of locating the power conversion external to the detector. The converters must operate in a large magnetic field and be able to survive both high doses of ionizing radiation and large neutron fluences. The presence of a large magnetic field necessitates the use of an air core inductor which is developed and discussed here. Noise measurements will be made to investigate the effect of the high frequency switching of the buck converter on the sensitive front end electronics. Radiation hardness of selected buck converters and mosfets will also be reported.
A combination of searches for a new resonance decaying into a Higgs boson pair is presented, using up to Formula Presented of Formula Presented collision data at Formula Presented recorded with the ...ATLAS detector at the LHC. The combination includes searches performed in three decay channels: Formula Presented, Formula Presented, and Formula Presented. No excess above the expected Standard Model background is observed and upper limits are set at the 95% confidence level on the production cross section of Higgs boson pairs originating from the decay of a narrow scalar resonance with mass in the range 251 GeV-5 TeV. The observed (expected) limits are in the range 0.96-600 fb (1.2-390 fb). The limits are interpreted in the type-I two-Higgs-doublet model and the minimal supersymmetric standard model, and constrain parameter space not previously excluded by other searches.
A search for the single production of a vectorlike top partner (Formula Presented) with mass greater than 1 TeV decaying into a Formula Presented boson and a top quark is presented, using the full ...Run 2 dataset corresponding to Formula Presented of Formula Presented collisions at Formula Presented, collected in 2015-2018 with the ATLAS detector at the Large Hadron Collider. The targeted final state is characterized by the presence of a pair of electrons or muons with opposite-sign charges which form a Formula Presented-boson candidate, as well as by the presence of Formula Presented-tagged jets and forward jets. Events with exactly two or at least three leptons are categorized into two independently optimized analysis channels. No significant excess above the background expectation is observed and the results from the two channels are statistically combined to set exclusion limits at 95% confidence level on the masses and couplings of Formula Presented. The results are interpreted in several benchmark scenarios to set limits on the mass and universal coupling strength (Formula Presented) of the vectorlike quark. For singlet Formula Presented quarks, Formula Presented values between 0.22 and 0.64 are excluded for masses between 1000 and 1975 GeV. For Formula Presented quarks in the doublet scenario, where the production cross section is much lower, Formula Presented values between 0.54 and 0.88 are excluded for masses between 1000 and 1425 GeV.
This paper presents a search for pair production of higgsinos, the supersymmetric partners of the Higgs bosons, in scenarios with gauge-mediated supersymmetry breaking. Each higgsino is assumed to ...decay into a Higgs boson and a nearly massless gravitino. The search targets events where each Higgs boson decays into Formula Presented, leading to a reconstructed final state with at least three energetic Formula Presented-jets and missing transverse momentum. Two complementary analysis channels are used, with each channel specifically targeting either low or high values of the higgsino mass. The low-mass (high-mass) channel exploits Formula Presented of Formula Presented data collected by the ATLAS detector during Run 2 of the Large Hadron Collider. No significant excess above the Standard Model prediction is found. At 95% confidence level, masses between 130 GeV and 940 GeV are excluded for higgsinos decaying exclusively into Higgs bosons and gravitinos. Exclusion limits as a function of the higgsino decay branching ratio to a Higgs boson are also reported.
A search for high-mass resonances decaying into a Formula Presented-lepton and a neutrino using proton-proton collisions at a center-of-mass energy of Formula Presented is presented. The full run 2 ...data sample corresponding to an integrated luminosity of Formula Presented recorded by the ATLAS experiment in the years 2015-2018 is analyzed. The Formula Presented-lepton is reconstructed in its hadronic decay modes and the total transverse momentum carried out by neutrinos is inferred from the reconstructed missing transverse momentum. The search for new physics is performed on the transverse mass between the Formula Presented-lepton and the missing transverse momentum. No excess of events above the Standard Model expectation is observed and upper exclusion limits are set on the Formula Presented production cross section. Heavy Formula Presented vector bosons with masses up to 5.0 TeV are excluded at 95% confidence level, assuming that they have the same couplings as the Standard Model Formula Presented boson. For nonuniversal couplings, Formula Presented bosons are excluded for masses less than 3.5-5.0 TeV, depending on the model parameters. In addition, model-independent limits on the visible cross section times branching ratio are determined as a function of the lower threshold on the transverse mass of the Formula Presented-lepton and missing transverse momentum.
Abstract
Yeast fermentation products (YFP) are thought to have a positive effect on response to heat stress in beef cattle, therefore an experiment was conducted to determine the effects of YFP on ...performance and serum metabolites in cattle exposed to a heat stressed environment. Twenty four Bos indicus/Bos taurus crossbred steers (BW = 274.3 ± 23.3 kg) were blocked according to initial body weight, then randomly assigned to treatment. Both treatments received 1% of their BW as a commercially available feed supplement, while grazing warm season bahiagrass pastures (n=8 pastures per treatment), during the summer months in southern Mississippi. Cattle fed YFP received 10 g per animal daily of Saccharomyces cerevisia blended in the supplement, while control (CON) simply received the supplement. On d 0, 28, and 56, cattle were weighed and blood samples were collected via jugular venipuncture for subsequent analysis of SUN and glucose. The addition of YFP did not affect BW (P > 0.05), ADG (P = 0.23) and total kg gained during grazing (P = 0.22). Nevertheless, feeding YFP tended to increase serum glucose at d 28 (P = 0.06; 41.2 vs 47.7 mg/dL for CON and YFP, respectively) and significantly increased serum glucose (P = 0.05) at d 56 (51.2 and 58.1 mg/dL for CON and YFP, respectively). No effects of YFP (P > 0.81) were noted with regards to SUN at any time during the study. Results suggest that YFP might have an effect on glucose metabolism, but did not affect performance.
A study was conducted to evaluate the effects of feeding graded concentrations of soybean hull pellets (SHP) on performance of weaned beef calves that were fed baleage. Sixty beef calves (216.2 ± 7.5 ...kg) were blocked by sex, stratified by BW and placed into 12 pens (five calves per pen), pens were randomly assigned treatments. Treatments were: 0.0%, 0.5% (0.5), or 1% (1.0) BW of soybean hull pellets fed daily while calves had ad libitum access to ryegrass baleage. Body weight and blood were collected on d 0, 28 and 47, for subsequent serum chemistry analyses. Baleage was weighed at offering and refusals were collected and weighed to calculate disappearance. Body weight tended to increase when either 0.5% or 1.0% SHP were fed (P < 0.1) at day 28; however increasing SHP increased BW at d 47 (P = 0.002). Increasing SHP resulted in greater ADG from d 0 to 28 (P < 0.003) and from d 0 to 47 (P < 0.003). Dry matter intake of baleage tended to be affected by SHP (P =0.06), with SHP decreasing baleage DMI; however no differences were noted between 0.5 and 1.0 SHP. From d 29 to 47 DMI of baleage decreased (P = 0.05) with SHP supplementation, but did not differ between supplement levels (P = 0.97). Similarly, total baleage DMI decreased with SHP (P = 0.01) but did not differ between supplement levels (P = 0.86). Results suggest that increasing SHP supplementation can improve performance without affecting baleage intake.
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