A novel autotransporter of uropathogenic Proteus mirabilis is both a cytotoxin and an agglutinin

One of the six predicted Proteus mirabilis autotransporters (ATs), ORF c2341, is predicted to contain a serine protease motif and was earlier identified as an immunogenic outer membrane protein in P. mirabilis . The 3.2 kb gene encodes a 117 kDa protein with a 58-amino-acid-long signal peptide, a 75-kDa-long N-terminal passenger domain and a 30-kDa-long C-terminal translocator. Affinity-purified 110 kDa AT exhibited chymotrypsin-like activity and hydrolysed N -Suc–Ala–Ala–Pro–Phe– p Na and N -Suc–Ala–Ala–Pro–Leu– p Na with a K M of 22 μM and 31 μM, respectively, under optimal pH of 8.5–9.0 in a Ca 2+ -dependent manner. Activity was inhibited by subtilase-specific inhibitors leupeptin and chymostatin. Both the cell-associated and purified form elicited cytopathic effects on cultured kidney and bladder epithelial cells. Substrate hydrolysis as well as cytotoxicity was associated with the passenger domain and was compromised upon mutation of any of the catalytic residues (Ser366, His147 and Asp533). At alkaline pH and optimal cell density, the AT also promoted autoaggregation of P. mirabilis and this function was independent of its protease activity. Cytotoxicity, autoaggregation and virulence were significantly reduced in an isogenic pta mutant of P. mirabilis . Proteus toxic agglutinin (Pta) represents a novel autotransported cytotoxin with no bacterial homologues that works optimally in the alkalinized urinary tract, a characteristic of urease-mediated urea hydrolysis during P. mirabilis infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73221/1/j.1365-2958.2008.06199.x.pd

Movement of cerebrospinal fluid tracer into brain parenchyma and outflow to nasal mucosa is reduced at 24 h but not 2 weeks post-stroke in mice

Background Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24 h after experimental stroke and that this reduces blood flow to ischaemic tissue. CSF outflow resistance is increased at this time point. We hypothesised that reduced transit of CSF through brain parenchyma and reduced outflow of CSF via the cribriform plate at 24 h after stroke may contribute to the previously identified post-stroke intracranial pressure elevation. Methods Using a photothrombotic permanent occlusion model of stroke in C57BL/6 adult male mice, we examined the movement of an intracisternally infused 0.5% Texas Red dextran throughout the brain and measured tracer efflux into the nasal mucosa via the cribriform plate at 24 h or two weeks after stroke. Brain tissue and nasal mucosa were collected ex vivo and imaged using fluorescent microscopy to determine the change in CSF tracer intensity in these tissues. Results At 24 h after stroke, we found that CSF tracer load was significantly reduced in brain tissue from stroke animals in both the ipsilateral and contralateral hemispheres when compared to sham. CSF tracer load was also reduced in the lateral region of the ipsilateral hemisphere when compared to the contralateral hemisphere in stroke brains. In addition, we identified an 81% reduction in CSF tracer load in the nasal mucosa in stroke animals compared to sham. These alterations to the movement of CSF-borne tracer were not present at two weeks after stroke. Conclusions Our data indicates that influx of CSF into the brain tissue and efflux via the cribriform plate are reduced 24 h after stroke. This may contribute to reported increases in intracranial pressure at 24 h after stroke and thus worsen stroke outcomes.K. E. Warren, K. G. Coupland, R. J. Hood, L. Kang, F. R. Walker, and N. J. Sprat

Astrobiologically Interesting Stars within 10 parsecs of the Sun

The existence of life based on carbon chemistry and water oceans relies upon planetary properties, chiefly climate stability, and stellar properties, such as mass, age, metallicity and Galactic orbits. The latter can be well constrained with present knowledge. We present a detailed, up-to-date compilation of the atmospheric parameters, chemical composition, multiplicity and degree of chromospheric activity for the astrobiologically interesting solar-type stars within 10 parsecs of the Sun. We determine their state of evolution, masses, ages and space velocities, and produce an optimized list of candidates that merit serious scientific consideration by the future space-based interferometry probes aimed at directly detecting Earth-sized extrasolar planets and seeking spectroscopic infrared biomarkers as evidence of photosynthetic life. The initially selected stars number 33 solar-type within the population of 182 stars (excluding late M-dwarfs) closer than 10 pc. A comprehensive and detailed data compilation for these objects is still essentially lacking: a considerable amount of recent data has so far gone unexplored in this context. We present 13 objects as the nearest "biostars", after eliminating multiple stars, young, chromospherically active, hard X-ray emitting stars, and low metallicity objects. Three of these "biostars", HD 1581, 109358 and 115617, closely reproduce most of the solar properties and are considered as premier targets. We show that approximately 7% of the nearby stars are optimally interesting targets for exobiology.Comment: 36 pages, recommended for publication in Astrobiolog

South Atlantic Interbasin Exchanges of Mass, Heat, Salt and Anthropogenic Carbon

The exchange of mass, heat, salt and anthropogenic carbon (Cant) between the South Atlantic, south of 24°S, and adjacent ocean basins is estimated from hydrographic data obtained during 2008-2009 using an inverse method. Transports of anthropogenic carbon are calculated across the western (Drake Passage), eastern (30°E) and northern (24°S) boundaries. The freshwater overturning transport of 0.09 Sv is southward, consistent with an overturning circulation that exports freshwater from the North Atlantic, and consistent with a bistable Meridional Overturning Circulation (MOC), under conditions of excess freshwater perturbation. At 30°E, net eastward Antarctic Circumpolar Current (ACC) transport, south of the Subtropical Front, is compensated by a 15.9±2.3 Sv westward flow along the Antarctic boundary. The region as a whole is a substantial sink for atmospheric anthropogenic carbon of 0.51±0.37 PgC yr-1, of which 0.18±0.12 PgC yr-1 accumulates and is stored within the water column. At 24°S, a 20.2 Sv meridional overturning is associated with a 0.11 PgC yr-1 Cant overturning. The remainder is transported into the Atlantic Ocean north of 24°S (0.28±0.16 PgC yr-1) and Indian sector of Southern Ocean (1.12±0.43 PgC yr-1), having been enhanced by inflow through Drake Passage (1.07±0.44 PgC yr-1). This underlines the importance of the South Atlantic as a crucial element of the anthropogenic carbon sink in the global oceans

An Observational Overview of Solar Flares

We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

A 680,000-person megastudy of nudges to encourage vaccination in pharmacies

Encouraging vaccination is a pressing policy problem. To assess whether text-based reminders can encourage pharmacy vaccination and what kinds of messages work best, we conducted a megastudy. We randomly assigned 689,693 Walmart pharmacy patients to receive one of 22 different text reminders using a variety of different behavioral science principles to nudge flu vaccination or to a business-as-usual control condition that received no messages. We found that the reminder texts that we tested increased pharmacy vaccination rates by an average of 2.0 percentage points, or 6.8%, over a 3-mo follow-up period. The most-effective messages reminded patients that a flu shot was waiting for them and delivered reminders on multiple days. The top-performing intervention included two texts delivered 3 d apart and communicated to patients that a vaccine was “waiting for you.” Neither experts nor lay people anticipated that this would be the best-performing treatment, underscoring the value of simultaneously testing many different nudges in a highly powered megastudy.https://www.pnas.org/content/pnas/119/6/e2115126119.full.pd