Pathologic changes in mice induced by subtilase cytotoxin, a potent new Escherichia coli AB(5) toxin that targets the endoplasmic reticulum

Subtilase cytotoxin (SubAB) is the prototype of a recently discovered AB₅ cytotoxin family produced by certain strains of Shiga toxigenic Escherichia coli (STEC). The catalytic A subunit is a highly specific subtilase-like serine protease that cleaves the endoplasmic reticulum chaperone BiP. The toxin is lethal for mice, but the pathology it induces is poorly understood. Here, we show that intraperitoneal injection of SubAB causes microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment in mice-characteristics typical of Shiga toxin-induced hemolytic uremic syndrome. SubAB caused extensive microvascular thrombosis and other histologic damage in the brain, kidneys, and liver, as well as dramatic splenic atrophy. Peripheral blood leukocyte levels were increased at 24 h; there was also significant neutrophil infiltration in the liver, kidneys, and spleen and toxin-induced apoptosis at these sites. These findings raise the possibility that SubAB directly contributes to pathology in humans infected with strains of STEC that produce both Shiga toxin and SubAB.Hui Wang, James C. Paton, and Adrienne W. Pato

The abortion-crime link: evidence from England and Wales

We use panel data from 1983 to 1997 for the 42 police force areas in England and Wales to test the hypothesis that legalizing abortion contributes to lower crime rates. We provide an advance on previous work by focusing on the impact of possible endogeneity of effective abortion rates with respect to crime. Our use of U.K. data allows us to exploit regional differences in the provision of free abortions to identify abortion rates. When we use a similar model and estimation methodology, we are able to replicate the negative association between abortion rates and reported crime found by Donohue and Levitt for the U.S. However, when we allow for the potential endogeneity of effective abortion rates with respect to crime, we find no clear connection between the two.

The Paton-Williams Debate on Universal Salvation and the Destiny of the Wicked

https://digitalcommons.acu.edu/crs_books/1540/thumbnail.jp

Computational Aspects of Protein Functionality

The purpose of this short article is to examine certain aspects of protein functionality with relation to some key organizing ideas. This is important from a computational viewpoint in order to take account of modelling both biological systems and knowledge of these systems. We look at some of the lexical dimensions of the function and how certain constructs can be related to underlying ideas. The pervasive computational metaphor is then discussed in relation to protein multifunctionality, and the specific case of von Willebrand factor as a ‘smart’ multifunctional protein is briefly considered. Some diagrammatic techniques are then introduced to better articulate protein function

Measurement of Martian boundary layer winds by the displacement of jettisoned lander hardware

Abstract Martian boundary layer wind speed and direction measurements, from a variety of locations, seasons and times, are provided. For each lander sent to Mars over the last four decades a unique record of the winds blowing during their descent is preserved at each landing site. By comparing images acquired from orbiting spacecraft of the impact points of jettisoned hardware, such as heat shields and parachutes, to a trajectory model the winds can be measured. We start our investigations with the Viking lander 1 mission and end with Schiaparelli. In-between we extract wind measurements based on observations of the Beagle 2, Spirit, Opportunity, Phoenix and Curiosity landing sites. With one exception the wind at each site during the lander’s descent were found to be   20 m s − 1 ), blowing from the north-west was required at a high altitude ( > 2 km) together with a gust close to the surface ( < 500 m altitude) originating from the north. All in all our investigations yielded a total of ten unique wind measurements in the PBL. One each from the Viking landers and one each from Beagle 2, Spirit, Opportunity and Schiaparelli. Two wind measurements, one above about 1 km altitude and one below, were possible from observations of the Curiosity and Phoenix landing site. Our findings are consistent with a turbulent PBL in the afternoon and calm PBL in the morning. When comparing our results to a GCM we found a good match in wind direction but not for wind speed. The information provided here makes available wind measurements previously unavailable to Mars atmosphere modellers and investigators.Peer reviewe

Autoinducer 2 signalling via the phosphotransferase FruA drives galactose utilization by Streptococcus pneumoniae resulting in hypervirulence

Communication between bacterial cells is crucial for the coordination of diverse cellular processes that facilitate environmental adaptation and, in the case of pathogenic species, virulence. This is achieved by the secretion and detection of small signaling molecules called autoinducers, a process termed quorum sensing. To date, the only signaling molecule recognized by both Gram-positive and Gramnegative bacteria is autoinducer 2 (AI-2), synthesized by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase) as a by-product of the activated methyl cycle. Homologues of LuxS are ubiquitous in bacteria, suggesting a key role in interspecies, as well as intraspecies, communication. Gram-negative bacteria sense and respond to AI-2 via the Lsr ABC transporter system or by the LuxP/LuxQ phosphorelay system. However, homologues of these systems are absent from Gram-positive bacteria and the AI-2 receptor is unknown. Here we show that in the major human pathogen Streptococcus pneumoniae, sensing of exogenous AI-2 is dependent on FruA, a fructose-specific phosphoenolpyruvate-phosphotransferase system that is highly conserved in Gram-positive pathogens. Importantly, AI-2 signaling via FruA enables the bacterium to utilize galactose as a carbon source and upregulates the Leloir pathway, thereby leading to increased production of capsular polysaccharide and a hypervirulent phenotype

Chandra X-Ray Spectroscopy Of The Very Early O Supergiant HD 93129A: Constraints On Wind Shocks And The Mass-Loss Rate

We present an analysis of both the resolved X-ray emission-line profiles and the broad-band X-ray spectrum of the O-2 If* star HD 93129A, measured with the Chandra High Energy Transmission Grating Spectrometer ( HETGS). This star is among the earliest and most massive stars in the Galaxy, and provides a test of the embedded wind-shock scenario in a very dense and powerful wind. A major new result is that continuum absorption by the dense wind is the primary cause of the hardness of the observed X-ray spectrum, while intrinsically hard emission from colliding wind shocks contributes less than 10 per cent of the X-ray flux. We find results consistent with the predictions of numerical simulations of the line-driving instability, including line broadening indicating an onset radius of X-ray emission of several tenths of R-*. Helium-like forbidden-to-intercombination line ratios are consistent with this onset radius, and inconsistent with being formed in a wind-collision interface with the star\u27s closest visual companion at a distance of 100 au. The broad-band X-ray spectrum is fitted with a dominant emission temperature of just kT = 0.6 keV along with significant wind absorption. The broad-band wind absorption and the line profiles provide two independent measurements of the wind mass-loss rate:. M = 5.2(-1.5)(+1.8) x 10(-6) and 6.8(-2.2)(+2.8) x 10(-6) M-circle dot yr(-1), respectively. This is the first consistent modelling of the X-ray line-profile shapes and broad-band X-ray spectral energy distribution in a massive star, and represents a reduction of a factor of 3-4 compared to the standard H alpha mass-loss rate that assumes a smooth wind