6,224 research outputs found

    Real Rigidity, Nominal Rigidity, and the Social Value of Information

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    Does welfare improve when firms are better informed about the state of the economy and can thus better coordinate their production and pricing decisions? We address this question in an elementary business-cycle model that highlights how the dispersion of information can impede both kinds of decisions and, in this sense, be the source of both real and nominal rigidity. Within this context we develop a taxonomy for how the social value of information depends on the two rigidities, on the sources of the business cycle, and on the conduct of monetary policy. (JEL D21, D82, D83, E32, E52

    Splenic Infarction: An Under-recognized Complication of Infectious Mononucleosis?

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    Splenic infarction is a rare complication of infectious mononucleosis. We describe 3 cases of splenic infarction attributed to infectious mononucleosis that we encountered within a 2-month period. We underscore the awareness of this potential complication of infectious mononucleosis and discuss the differential diagnosis of splenic infarction, including infectious etiologies. While symptomatic management is usually sufficient for infectious mononucleosis-associated splenic infarction, close monitoring for other complications, including splenic rupture, is mandated

    Unobscured Type 2 Active Galactic Nuclei

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    Type 2 active galactic nuclei (AGNs) with intrinsically weak broad emission lines (BELs) would be exceptions to the unified model. After examining a number of proposed candidates critically, we find that the sample is contaminated significantly by objects with BELs of strengths indicating that they actually contain intermediate-type AGNs, plus a few Compton-thick sources as revealed by extremely low ratios of X-ray to nuclear IR luminosities. We develop quantitative metrics that show two (NGC 3147 and NGC 4594) of the remaining candidates to have BELs 2-3 orders of magnitude weaker than those of typical type 1 AGNs. Several more galaxies remain as candidates to have anomalously weak BELs, but this status cannot be confirmed with the existing information. Although the parent sample is poorly defined, the two confirmed objects are well under 1% of its total number of members, showing that the absence of a BEL is possible, but very uncommon in AGN. We evaluate these two objects in detail using multi-wavelength measurements including new IR data obtained with Spitzer and ground-based optical spectropolarimeteric observations. They have little X-ray extinction with N_H < ~10^(21) cm^(–2). Their IR spectra show strong silicate emission (NGC 4594) or weak aromatic features on a generally power-law continuum with a suggestion of silicates in emission (NGC 3147). No polarized BEL is detected in NGC 3147. These results indicate that the two unobscured type 2 objects have circumnuclear tori that are approximately face-on. Combined with their X-ray and optical/UV properties, this behavior implies that we have an unobscured view of the nuclei and thus that they have intrinsically weak BELs. We compare their properties with those of the other less-extreme candidates. We then compare the distributions of bolometric luminosities and accretion rates of these objects with theoretical models that predict weak BELs

    RidA proteins prevent metabolic damage inflicted by PLP-dependent dehydratases in all domains of life

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    ABSTRACT Pyridoxal 5′-phosphate (PLP) is a coenzyme synthesized by all forms of life. Relevant to the work reported here is the mechanism of the PLP-dependent threonine/serine dehydratases, which generate reactive enamine/imine intermediates that are converted to keto acids by members of the RidA family of enzymes. The RidA protein of Salmonella enterica serovar Typhimurium LT2 is the founding member of this broadly conserved family of proteins (formerly known as YjgF/YER057c/UK114). RidA proteins were recently shown to be enamine deaminases. Here we demonstrate the damaging potential of enamines in the absence of RidA proteins. Notably, S. enterica strains lacking RidA have decreased activity of the PLP-dependent transaminase B enzyme IlvE, an enzyme involved in branched-chain amino acid biosynthesis. We reconstituted the threonine/serine dehydratase (IlvA)-dependent inhibition of IlvE in vitro, show that the in vitro system reflects the mechanism of RidA function in vivo, and show that IlvE inhibition is prevented by RidA proteins from all domains of life. We conclude that 2-aminoacrylate (2AA) inhibition represents a new type of metabolic damage, and this finding provides an important physiological context for the role of the ubiquitous RidA family of enamine deaminases in preventing damage by 2AA. IMPORTANCE External stresses that disrupt metabolic components can perturb cellular functions and affect growth. A similar consequence is expected if endogenously generated metabolites are reactive and persist in the cellular environment. Here we show that the metabolic intermediate 2-aminoacrylate (2AA) causes significant cellular damage if allowed to accumulate aberrantly. Furthermore, we show that the widely conserved protein RidA prevents this accumulation by facilitating conversion of 2AA to a stable metabolite. This work demonstrates that the reactive metabolite 2AA, previously considered innocuous in the cell due to a short half-life in aqueous solution, can survive in the cellular environment long enough to cause damage. This work provides insights into the roles and persistence of reactive metabolites in vivo and shows that the RidA family of proteins is able to prevent damage caused by a reactive intermediate that is created as a consequence of PLP-dependent chemistry

    Effects of exercise on depression in adults with arthritis: a systematic review with meta-analysis of randomized controlled trials

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    Introduction Previous randomized controlled trials have led to conflicting findings regarding the effects of exercise on depressive symptoms in adults with arthritis and other rheumatic conditions (AORC). The purpose of this study was to use the meta-analytic approach to resolve these discrepancies. Methods The inclusion criteria were: (1) randomized controlled trials, (2) exercise (aerobic, strength training, or both) ≥4 weeks, (3) comparative control group, (4) adults with osteoarthritis, rheumatoid arthritis, fibromyalgia or systemic lupus erythematosus, (5) published studies in any language since January 1, 1981 and (6) depressive symptoms assessed. Studies were located by searching 10 electronic databases, cross-referencing, hand searching and expert review. Dual-selection of studies and data abstraction was performed. Hedge’s standardized mean difference effect size (g) was calculated for each result and pooled using random-effects models, an approach that accounts for heterogeneity. Non-overlapping 95% confidence intervals (CI) were considered statistically significant. Heterogeneity based on fixed-effect models was estimated using Q and I 2 with alpha values ≤0.10 for Q considered statistically significant. Results Of the 500 citations reviewed, 2,449 participants (1,470 exercise, 979 control) nested within 29 studies were included. Length of training, reported as mean ± standard deviation (±SD) was 19 ± 16 weeks, frequency 4 ± 2 times per week and duration 34 ± 17 minutes per session. Overall, statistically significant exercise minus control group reductions were found for depressive symptoms (g = −0.42, 95% CI, −0.58, −0.26, Q = 126.9, P \u3c0.0001, I 2 = 73.2%). The number needed-to-treat was 7 (95% CI, 6 to 11) with an estimated 3.1 million (95% CI, 2.0 to 3.7) United States adults not currently meeting physical activity guidelines improving their depressive symptoms if they began and maintained a regular exercise program. Using Cohen’s U3 Index, the percentile reduction was 16.4% (95% CI, 10.4% to 21.9%). All studies were considered to be at high risk of bias with respect to blinding of participants and personnel to group assignment

    Invasion of the central nervous system by Cryptococcus neoformans requires a secreted fungal metalloprotease.

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    UnlabelledCryptococcus spp. cause life-threatening fungal infection of the central nervous system (CNS), predominantly in patients with a compromised immune system. Why Cryptococcus&nbsp;neoformans has this remarkable tropism for the CNS is not clear. Recent research on cerebral pathogenesis of C.&nbsp;neoformans revealed a predominantly transcellular migration of cryptococci across the brain endothelium; however, the identities of key fungal virulence factors that function specifically to invade the CNS remain unresolved. Here we found that a novel, secreted metalloprotease (Mpr1) that we identified in the extracellular proteome of C.&nbsp;neoformans (CnMpr1) is required for establishing fungal disease in the CNS. Mpr1 belongs to a poorly characterized M36 class of fungalysins that are expressed in only some fungal species. A strain of C.&nbsp;neoformans lacking the gene encoding Mpr1 (mpr1Δ) failed to breach the endothelium in an in vitro model of the human blood-brain barrier (BBB). A mammalian host infected with the mpr1Δ null strain demonstrated significant improvement in survival due to a reduced brain fungal burden and lacked the brain pathology commonly associated with cryptococcal disease. The in vivo studies further indicate that Mpr1 is not required for fungal dissemination and Mpr1 likely targets the brain endothelium specifically. Remarkably, the sole expression of CnMPR1 in Saccharomyces&nbsp;cerevisiae resulted in a robust migration of yeast cells across the brain endothelium, demonstrating Mpr1's specific activity in breaching the BBB and suggesting that Mpr1 may function independently of the hyaluronic acid-CD44 pathway. This distinct role for Mpr1 may develop into innovative treatment options and facilitate a brain-specific drug delivery platform.ImportanceCryptococcus neoformans is a medically relevant fungal pathogen causing significant morbidity and mortality, particularly in immunocompromised individuals. An intriguing feature is its strong neurotropism, and consequently the hallmark of cryptococcal disease is a brain infection, cryptococcal meningoencephalitis. For C.&nbsp;neoformans to penetrate the central nervous system (CNS), it first breaches the blood-brain barrier via a transcellular pathway; however, the identities of fungal factors required for this transmigration remain largely unknown. In an effort to identify extracellular fungal proteins that could mediate interactions with the brain endothelium, we undertook a proteomic analysis of the extracellular proteome and identified a secreted metalloprotease (Mpr1) belonging to the M36 class of fungalysins. Here we found that Mpr1 promotes migration of C.&nbsp;neoformans across the brain endothelium and into the CNS by facilitating attachment of cryptococci to the endothelium surface, thus underscoring the critical role of M36 proteases in fungal pathogenesis

    Examination of the Relationship between In-Store Environmental Factors and Fruit and Vegetable Purchasing among Hispanics.

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    Retail food environments have received attention for their influence on dietary behaviors and for their nutrition intervention potential. To improve diet-related behaviors, such as fruit and vegetable (FV) purchasing, it is important to examine its relationship with in-store environmental characteristics. This study used baseline data from the "El Valor de Nuestra Salud" study to examine how in-store environmental characteristics, such as product availability, placement and promotion, were associated with FV purchasing among Hispanic customers in San Diego County. Mixed linear regression models indicated that greater availability of fresh FVs was associated with a 0.36increaseinFVpurchasing(p=0.01).Placementvariables,specificallyeachadditionalsquarefootofdisplayspacededicatedtoFVs(p=0.01)andeachadditionalfreshFVdisplay(p=0.01),wereassociatedwitha0.36 increase in FV purchasing (p = 0.01). Placement variables, specifically each additional square foot of display space dedicated to FVs (p = 0.01) and each additional fresh FV display (p = 0.01), were associated with a 0.02 increase and 0.29decrease,respectively,inFVpurchasing.IntroducingFVpromotionsinthefinalmodelwasnotrelatedtoFVpurchasing.Exploratoryanalysesindicatedthatmenreportedspending0.29 decrease, respectively, in FV purchasing. Introducing FV promotions in the final model was not related to FV purchasing. Exploratory analyses indicated that men reported spending 3.69 fewer dollars on FVs compared to women, controlling for covariates (p = 0.02). These results can help inform interventions targeting in-store environmental characteristics to encourage FV purchasing among Hispanics

    A longitudinal study of muscle rehabilitation in the lower leg after cast removal using Magnetic Resonance Imaging and strength assessment

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    Acknowledgements We thank the A&E nurses and plaster technicians for identifying suitable patients, the MRI radiographers for performing the scanning, Dr Scott Semple for invaluable help in some of the pilot studies and Mr E. C. Stevenson for constructing the footrest used in the scanner. We are very grateful to the dedicated patients themselves who gave considerable amounts of time to come in for scanning, exercise and assessment during the course of this study.Peer reviewedPublisher PD
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