New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection

PublishedArticleThe specific and rapid detection of Enterobacteriaceae, the most frequent cause of gram-negative bacterial infections in humans, remains a major challenge. We developed a non-invasive method to rapidly detect systemic Yersinia enterocolitica infections using immunoPET (antibody-targeted positron emission tomography) with [64Cu]NODAGA-labeled Yersinia-specific polyclonal antibodies targeting the outer membrane protein YadA. In contrast to the tracer [18F]FDG, [64Cu]NODAGA-YadA uptake co-localized in a dose dependent manner with bacterial lesions of Yersinia-infected mice, as detected by magnetic resonance (MR) imaging. This was accompanied by elevated uptake of [64Cu]NODAGA-YadA in infected tissues, in ex vivo biodistribution studies, whereas reduced uptake was observed following blocking with unlabeled anti-YadA antibody. We show, for the first time, a bacteria-specific, antibody-based, in vivo imaging method for the diagnosis of a Gram-negative enterobacterial infection as a proof of concept, which may provide new insights into pathogen-host interactions.The research leading to these results has received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement n°602820, from the European Social Fund Baden-Württemberg (to SEA), and from the Deutsche Forschungsgemeinschaft (grant WI 3777/1-2; to SW)

Potential of measured relative shifts in collision cross section values for biotransformation studies.

Ion mobility spectrometry-mass spectrometry (IMS-MS) separates gas phase ions due to differences in drift time from which reproducible and analyte-specific collision cross section (CCS) values can be derived. Internally conducted in vitro and in vivo metabolism (biotransformation) studies indicated repetitive shifts in measured CCS values (CCSmeas) between parent drugs and their metabolites. Hence, the purpose of the present article was (i) to investigate if such relative shifts in CCSmeas were biotransformation-specific and (ii) to highlight their potential benefits for biotransformation studies. First, mean CCSmeas values of 165 compounds were determined (up to n = 3) using a travelling wave IMS-MS device with nitrogen as drift gas (TWCCSN2, meas). Further comparison with their predicted values (TWCCSN2, pred, Waters CCSonDemand) resulted in a mean absolute error of 5.1%. Second, a reduced data set (n = 139) was utilized to create compound pairs (n = 86) covering eight common types of phase I and II biotransformations. Constant, discriminative, and almost non-overlapping relative shifts in mean TWCCSN2, meas were obtained for demethylation (- 6.5 ± 2.1 Å2), oxygenation (hydroxylation + 3.8 ± 1.4 Å2, N-oxidation + 3.4 ± 3.3 Å2), acetylation (+ 13.5 ± 1.9 Å2), sulfation (+ 17.9 ± 4.4 Å2), glucuronidation (N-linked: + 41.7 ± 7.5 Å2, O-linked: + 38.1 ± 8.9 Å2), and glutathione conjugation (+ 49.2 ± 13.2 Å2). Consequently, we propose to consider such relative shifts in TWCCSN2, meas (rather than absolute values) as well for metabolite assignment/confirmation complementing the conventional approach to associate changes in mass-to-charge (m/z) values between a parent drug and its metabolite(s). Moreover, the comparison of relative shifts in TWCCSN2, meas significantly simplifies the mapping of metabolites into metabolic pathways as demonstrated

Data from: Mammal-induced trophic cascades in invertebrate food webs are modulated by grazing intensity in subalpine grassland

1. Even though mammalian herbivores can exert strong indirect effects on other animals by altering the vegetation, the study of trophic cascades retains a focus on apex predators and their top-down forces. Bottom-up trophic interaction chains induced by mammalian herbivores, particularly in invertebrate food webs, remain largely unexplored. 2. We tested whether effects of mammalian herbivores on the vegetation ricochet back up several trophic levels of the invertebrate food web. We further tested two alternative hypotheses: the strength of herbivore-induced indirect interactions either increases with plant productivity because of a concurrent higher grazing intensity, or it decreases because of a higher plant tolerance to grazing. 3. We progressively excluded large, medium, and small herbivorous mammals from replicated plots of 6 m2 in productive, intensively grazed short-grass vegetation and less productive, less intensively grazed tall-grass vegetation of subalpine grasslands. We measured vegetation quantity, quality, structure, and composition, and determined the abundance of invertebrate herbivores, detritivores, omnivores, and predators. We used Structural Equation Modelling to test vegetation-mediated cascading effects of the different mammalian herbivores across different trophic groups of invertebrates. 4. In the short-grass vegetation, mammals caused changes in vegetation quantity and thickness. These changes directly affected detritivorous and predatory invertebrate abundance, yet indirectly affected predatory and omnivorous invertebrates through a bottom-up trophic cascade via changes in herbivorous invertebrate abundance. In the tall-grass vegetation, mammal-induced changes in vegetation quality and composition affected detritivorous invertebrates and in turn omnivorous invertebrates, but these cascading effects were weaker than those in the short-grass vegetation. Smaller mammals were at least as important as large mammals in structuring the invertebrate food web. 5. Our results demonstrate that differently sized mammalian herbivores can trigger trophic cascades in the local invertebrate food web. Our findings further support the hypothesis that herbivore-induced indirect interactions are stronger in more productive systems because of higher foraging intensity, as opposed to the hypothesis that a higher grazing tolerance of plants should dampen herbivore-induced indirect interactions in productive systems

Data from: Mammal-induced trophic cascades in invertebrate food webs are modulated by grazing intensity in subalpine grassland

1. Even though mammalian herbivores can exert strong indirect effects on other animals by altering the vegetation, the study of trophic cascades retains a focus on apex predators and their top-down forces. Bottom-up trophic interaction chains induced by mammalian herbivores, particularly in invertebrate food webs, remain largely unexplored. 2. We tested whether effects of mammalian herbivores on the vegetation ricochet back up several trophic levels of the invertebrate food web. We further tested two alternative hypotheses: the strength of herbivore-induced indirect interactions either increases with plant productivity because of a concurrent higher grazing intensity, or it decreases because of a higher plant tolerance to grazing. 3. We progressively excluded large, medium, and small herbivorous mammals from replicated plots of 6 m2 in productive, intensively grazed short-grass vegetation and less productive, less intensively grazed tall-grass vegetation of subalpine grasslands. We measured vegetation quantity, quality, structure, and composition, and determined the abundance of invertebrate herbivores, detritivores, omnivores, and predators. We used Structural Equation Modelling to test vegetation-mediated cascading effects of the different mammalian herbivores across different trophic groups of invertebrates. 4. In the short-grass vegetation, mammals caused changes in vegetation quantity and thickness. These changes directly affected detritivorous and predatory invertebrate abundance, yet indirectly affected predatory and omnivorous invertebrates through a bottom-up trophic cascade via changes in herbivorous invertebrate abundance. In the tall-grass vegetation, mammal-induced changes in vegetation quality and composition affected detritivorous invertebrates and in turn omnivorous invertebrates, but these cascading effects were weaker than those in the short-grass vegetation. Smaller mammals were at least as important as large mammals in structuring the invertebrate food web. 5. Our results demonstrate that differently sized mammalian herbivores can trigger trophic cascades in the local invertebrate food web. Our findings further support the hypothesis that herbivore-induced indirect interactions are stronger in more productive systems because of higher foraging intensity, as opposed to the hypothesis that a higher grazing tolerance of plants should dampen herbivore-induced indirect interactions in productive systems

Regional Economic Policy in Europe: new challenges for theory, empirics and normative interventions

Regional Economic Policy in Europe presents a tightly focused selection of policy, empirical and theoretical perspectives on contemporary dimensions of regional economic policy in the EU. It concentrates on three areas; the dissimilarities and resulting convergence of disparate regions within the EU; the localisation of economic activities and how regions can understand and manage them and, finally, the experiences and lessons that can be drawn from European regional policy. While exploring EU cohesion and regional development more widely, the book also examines Spanish, Belgian and Eastern European experiences on growth, human capital, foreign investment and technological spillovers.\ud \ud This up-to-date and thoroughly researched study is one that will be appreciated by academics and researchers of European studies and regional economics in Europe. Policymakers will also find the conclusions reached within the pages of this book invaluable

New challenges in regional economics: an overview

[Extract] Since its beginnings, regional economics has tried to explain the uneven economic development across the spatial landscape, and the different behaviour of regions in response to local and global changes. The main challenges for this discipline are, thus, the identification of the sources of varying regional performances, and the provision of assistance to policy makers for dealing with social and economic problems arising from regional disparities.\ud \ud Especially with the accession of twelve new Member States between 2004 and 2007, the disparities within the EU in economic, social and territorial terms have increased tremendously. For instance the GDP per capita in Luxembourg in purchasing power parities was, in 2006, more than 280 percent of the EU27 average, while Bulgaria and Romania were both about 60 percent below that average (Eurostat 2007). But also within single Member States, growth performance is concentrated in the most dynamic regions as, for example, capital regions and urban centres, and lagging behind in, above all, rural and peripheral areas

Data from: Mammalian herbivores affect leafhoppers associated with specific plant functional types at different timescales

1. Theory predicts that mammalian herbivores affect the quantity and quality of plants on which they preferentially feed in the short term. In the longer term, they can promote either preferred or less preferred plants, depending on whether preferred plants are adapted or sensitive to grazing. Less clear are the short- and long-term responses of herbivorous insects to mammalian herbivory, and how these responses depend on the specific plants or plant functional types on which the insects feed. 2. We progressively excluded large, medium, and small mammals for five growing seasons in two subalpine vegetation types with long-term differences in mammalian grazing intensity. Short-grass vegetation has a history of intensive grazing, while tall-grass vegetation has been grazed less intensively. We tested whether mammals altered the abundance and body size of leafhoppers specialized on specific plant functional types (grasses, sedges, forbs, or legumes/forbs), distinguishing between short-term (exclosures) and long-term (vegetation types) differences in mammalian grazing pressure. Furthermore, we assessed whether leafhoppers’ responses were explained by changes in biomass or quality of the plant functional types on which they feed. 3. In the short term, mammal exclosures increased the abundance of grass- and forb-feeding leafhoppers via increases in the biomass of grasses and forbs, regardless of vegetation type. Both grasses and forbs are preferred food plants of mammals. In the long term, the biomass of sedges, which are less preferred by mammals, increased in the less intensively grazed tall-grass vegetation. This resulted in a higher abundance of sedge-feeding leafhoppers. The small size of these sedge feeders lowered the average leafhopper body size in the tall-grass vegetation. Plant nutritional quality did not explain any effects of exclusions or vegetation types. 4. Our results demonstrate that both short- and long-term effects of mammalian herbivores on the biomass of specific plant functional types caused concurrent changes in the abundance of specialized herbivorous insects, which scaled up to community-wide shifts in insect body size, a key life-history trait. A plant-functional-type approach can thus help to predict how overabundance or extinction of mammalian herbivores impacts on other components of the food web at various timescales

Data_JAE-2016-00436.R4

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