High-Pressure Amorphous Nitrogen

The phase diagram and stability limits of diatomic solid nitrogen have been explored in a wide pressure--temperature range by several optical spectroscopic techniques. A newly characterized narrow-gap semiconducting phase $\eta$ has been found to exist in a range of 80--270 GPa and 10--510 K. The vibrational and optical properties of the $\eta$ phase produced under these conditions indicate that it is largely amorphous and back transforms to a new molecular phase. The band gap of the $\eta$ phase is found to decrease with pressure indicating possible metallization by band overlap above 280 GPa.Comment: 5 pages, 4 figure

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

Boolean network simulations for life scientists

Modern life sciences research increasingly relies on computational solutions, from large scale data analyses to theoretical modeling. Within the theoretical models Boolean networks occupy an increasing role as they are eminently suited at mapping biological observations and hypotheses into a mathematical formalism. The conceptual underpinnings of Boolean modeling are very accessible even without a background in quantitative sciences, yet it allows life scientists to describe and explore a wide range of surprisingly complex phenomena. In this paper we provide a clear overview of the concepts used in Boolean simulations, present a software library that can perform these simulations based on simple text inputs and give three case studies. The large scale simulations in these case studies demonstrate the Boolean paradigms and their applicability as well as the advanced features and complex use cases that our software package allows. Our software is distributed via a liberal Open Source license and is freely accessible fro

O Antigen Allows B. parapertussis to Evade B. pertussis Vaccine–Induced Immunity by Blocking Binding and Functions of Cross-Reactive Antibodies

Although the prevalence of Bordetella parapertussis varies dramatically among studies in different populations with different vaccination regimens, there is broad agreement that whooping cough vaccines, composed only of B. pertussis antigens, provide little if any protection against B. parapertussis. In C57BL/6 mice, a B. pertussis whole-cell vaccine (wP) provided modest protection against B. parapertussis, which was dependent on IFN-γ. The wP was much more protective against an isogenic B. parapertussis strain lacking O-antigen than its wild-type counterpart. O-antigen inhibited binding of wP–induced antibodies to B. parapertussis, as well as antibody-mediated opsonophagocytosis in vitro and clearance in vivo. aP–induced antibodies also bound better in vitro to the O-antigen mutant than to wild-type B. parapertussis, but aP failed to confer protection against wild-type or O antigen–deficient B. parapertussis in mice. Interestingly, B. parapertussis–specific antibodies provided in addition to either wP or aP were sufficient to very rapidly reduce B. parapertussis numbers in mouse lungs. This study identifies a mechanism by which one pathogen escapes immunity induced by vaccination against a closely related pathogen and may explain why B. parapertussis prevalence varies substantially between populations with different vaccination strategies

A Novel Sensor Kinase Is Required for Bordetella bronchiseptica To Colonize the Lower Respiratory Tract▿

Bacterial virulence is influenced by the activity of two-component regulator systems (TCSs), which consist of membrane-bound sensor kinases that allow bacteria to sense the external environment and cytoplasmic, DNA-binding response regulator proteins that control appropriate gene expression. Respiratory pathogens of the Bordetella genus require the well-studied TCS BvgAS to control the expression of many genes required for colonization of the mammalian respiratory tract. Here we describe the identification of a novel gene in Bordetella bronchiseptica, plrS, the product of which shares sequence homology to several NtrY-family sensor kinases and is required for B. bronchiseptica to colonize and persist in the lower, but not upper, respiratory tract in rats and mice. The plrS gene is located immediately 5′ to and presumably cotranscribed with a gene encoding a putative response regulator, supporting the idea that PlrS and the product of the downstream gene may compose a TCS. Consistent with this hypothesis, the PlrS-dependent colonization phenotype requires a conserved histidine that serves as the site of autophosphorylation in other sensor kinases, and in strains lacking plrS, the production and/or cellular localization of several immune-recognized proteins is altered in comparison to that in the wild-type strain. Because plrS is required for colonization and persistence only in the lower respiratory tract, a site where innate and adaptive immune mechanisms actively target infectious agents, we hypothesize that its role may be to allow Bordetella to resist the host immune response