723 research outputs found
Bacillus anthracis requires siderophore biosynthesis for growth in macrophages and mouse virulence
Systemic anthrax infections can be characterized as proceeding in stages, beginning with an early intracellular establishment stage within phagocytes that is followed by extracelluar stages involving massive bacteraemia, sepsis and death. Because most bacteria require iron, and the host limits iron availability through homeostatic mechanisms, we hypothesized that B. anthracis requires a high-affinity mechanism of iron acquisition during its growth stages. Two putative types of siderophore synthesis operons, named B acillus a nthracis c atechol, bac (anthrabactin), and a nthrax s iderophore b iosynthesis, asb (anthrachelin), were identified. Directed gene deletions in both anthrabactin and anthrachelin pathways were generated in a B. anthracis (Sterne) 34F2 background resulting in mutations in asbA and bacCEBF . A decrease in siderophore production was observed during iron-depleted growth in both the δ asbA and δ bacCEBF strains, but only the δ asbA strain was attenuated for growth under these conditions. In addition, the δ asbA strain was severely attenuated both for growth in macrophages (Mφ) and for virulence in mice. In contrast, the δ bacCEBF strain did not differ phenotypically from the parental strain. These findings support a requirement for anthrachelin but not anthrabactin in iron assimilation during the intracellular stage of anthrax.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72033/1/j.1365-2958.2003.03861.x.pd
Systemic criticality
With high certainty, extreme weather events will intensify in their impact within the next 10 years due to climate change-induced increases in hazard probability of occurrence and simultaneous increases in socio-economic vulnerability. Data from previous mega-disasters show that losses from disruptions of critical services surpass the value of direct damages in the exposed areas because critical infrastructures [CI] are increasingly (inter-) dependent. Local events may have global impacts. Systemic criticality, which describes the relevance of a critical infrastructure due to its positioning within the system, needs to be addressed to reduce the likelihood of cascading effects. This paper presents novel approaches to operationalise and assess systemic criticality. Firstly, the paper introduces systemic cascade potential as a measurement of systemic criticality. It takes the relevance of a sector and the relevance of its interdependencies into account to generate a relative value of systemic importance for a CI sector. Secondly, an exemplary sectoral assessment of the road network allows reflecting the spatial manifestation of the first level of cascading effects. It analyses the impact of traffic interruptions on the accessibility of critical facilities to point out the systemically most critical segments of the municipal road network. To further operationalise the spatial dimension of criticality, a normative assertion determining the worthiness of protection of system components is required. A nationwide spatial flood protection plan incorporates this aspect in Germany for the first time. Its formal approval process was initiated in February 2020
Role of the gerP Operon in Germination and Outgrowth of Bacillus anthracis Spores
Germination of Bacillus anthracis spores occurs when nutrients such as amino acids or purine nucleosides stimulate specific germinant receptors located in the spore inner membrane. The gerPABCDEF operon has been suggested to play a role in facilitating the interaction between germinants and their receptors in spores of Bacillus subtilis and Bacillus cereus. B. anthracis mutants containing deletions in each of the six genes belonging to the orthologue of the gerPABCDEF operon, or deletion of the entire operon, were tested for their ability to germinate. Deletion of the entire gerP operon resulted in a significant delay in germination in response to nutrient germinants. These spores eventually germinated to levels equivalent to wild-type, suggesting that an additional entry point for nutrient germinants may exist. Deletions of each individual gene resulted in a similar phenotype, with the exception of ΔgerPF, which showed no obvious defect. The removal of two additional gerPF-like orthologues was necessary to achieve the germination defect observed for the other mutants. Upon physical removal of the spore coat, the mutant lacking the full gerP operon no longer exhibited a germination defect, suggesting that the GerP proteins play a role in spore coat permeability. Additionally, each of the gerP mutants exhibited a severe defect in calcium-dipicolinic acid (Ca-DPA)–dependent germination, suggesting a role for the GerP proteins in this process. Collectively, these data implicate all GerP proteins in the early stages of spore germination
Crystal structure of the anthrax lethal factor
Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax(1-3). It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways(4-6). Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62772/1/414229a0.pd
The negative footprint illusion is exacerbated by the numerosity of environment-friendly additions: unveiling the underpinning mechanisms
The addition of environmentally friendly items to conventional items sometimes leads people to believe that the carbon footprint of the entire set decreases rather than increases. This negative footprint illusion is supposedly underpinned by an averaging bias: people base environmental impact estimates not on the total impact of items but on their average. Here, we found that the illusion’s magnitude increased with the addition of a greater number of “green” items when the number of conventional items remained constant (Studies 1 and 2), supporting the averaging-bias account. We challenged this account by testing what happens when the number of items in the conventional and “green” categories vary while holding the ratio between the two categories constant (Study 3). At odds with the averaging-bias account, the magnitude of the illusion increased as the category size increased, revealing a category-size bias, and raising questions about the interplay between these biases in the illusion
Planning for Sustainability in Small Municipalities: The Influence of Interest Groups, Growth Patterns, and Institutional Characteristics
How and why small municipalities promote sustainability through planning efforts is poorly understood. We analyzed ordinances in 451 Maine municipalities and tested theories of policy adoption using regression analysis.We found that smaller communities do adopt programs that contribute to sustainability relevant to their scale and context. In line with the political market theory, we found that municipalities with strong environmental interests, higher growth, and more formal governments were more likely to adopt these policies. Consideration of context and capacity in planning for sustainability will help planners better identify and benefit from collaboration, training, and outreach opportunities
Reaction time performance in ADHD: improvement under fast-incentive condition and familial effects
ABSTRACT Background Reaction time (RT) variability is one of the strongest findings to emerge in cognitive-experimental research of attention deficit hyperactivity disorder (ADHD). We set out to confirm the association between ADHD and slow and variable RTs and investigate the degree to which RT performance improves under fast event rate and incentives. Using a group familial correlation approach, we tested the hypothesis that there are shared familial effects on RT performance and ADHD. Method A total of 144 ADHD combined-type probands, 125 siblings of the ADHD probands and 60 control participants, ages 6-18, performed a four-choice RT task with baseline and fast-incentive conditions. Results ADHD was associated with slow and variable RTs, and with greater improvement in speed and RT variability from baseline to fast-incentive condition. RT performance showed shared familial influences with ADHD. Under the assumption that the familial effects represent genetic influences, the proportion of the phenotypic correlation due to shared familial influences was estimated as 60-70%. Conclusions The data are inconsistent with models that consider RT variability as reflecting a stable cognitive deficit in ADHD, but instead emphasize the extent to which energetic or motivational factors can have a greater effect on RT performance in ADHD. The findings support the role of RT variability as an endophenotype mediating the link between genes and ADH
Multi-Messenger Astronomy with Extremely Large Telescopes
The field of time-domain astrophysics has entered the era of Multi-messenger
Astronomy (MMA). One key science goal for the next decade (and beyond) will be
to characterize gravitational wave (GW) and neutrino sources using the next
generation of Extremely Large Telescopes (ELTs). These studies will have a
broad impact across astrophysics, informing our knowledge of the production and
enrichment history of the heaviest chemical elements, constrain the dense
matter equation of state, provide independent constraints on cosmology,
increase our understanding of particle acceleration in shocks and jets, and
study the lives of black holes in the universe. Future GW detectors will
greatly improve their sensitivity during the coming decade, as will
near-infrared telescopes capable of independently finding kilonovae from
neutron star mergers. However, the electromagnetic counterparts to
high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus
demand ELT capabilities for characterization. ELTs will be important and
necessary contributors to an advanced and complete multi-messenger network.Comment: White paper submitted to the Astro2020 Decadal Surve
The state of the Martian climate
60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
Transcriptional Profiling of Bacillus anthracis Sterne (34F2) during Iron Starvation
Lack of available iron is one of many environmental challenges that a bacterium encounters during infection and adaptation to iron starvation is important for the pathogen to efficiently replicate within the host. Here we define the transcriptional response of B. anthracis Sterne (34F2) to iron depleted conditions. Genome-wide transcript analysis showed that B. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known and candidate virulence factors. Two genes encoding putative internalin proteins were chosen for further study. Deletion of either gene (GBAA0552 or GBAA1340) resulted in attenuation in a murine model of infection. This attenuation was amplified in a double mutant strain. These data define the transcriptional changes induced during growth in low iron conditions and illustrate the potential of this dataset in the identification of putative virulence determinants for future study
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