Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macriphages

Clinical, but not experimental evidence has suggested that air pollution particulate matter (PM) aggravates myocardial infarction (MI). Here, we aimed to describe mechanisms and consequences of PM exposure in an experimental model of MI. C57BL/6J mice were challenged with a PM surrogate (Residual Oil Fly Ash, ROFA) by intranasal installation before MI was induced by permanent ligation of the left anterior descending coronary artery. Histological analysis of the myocardium 7 days after MI demonstrated an increase in infarct area and enhanced inflammatory cell recruitment in ROFA-exposed mice. Mechanistically, ROFA exposure increased levels of the circulating pro-inflammatory cytokines TNF-α, IL-6, and MCP-1, activated myeloid and endothelial cells, and enhanced leukocyte recruitment to the peritoneal cavity and the vascular endothelium. Notably, these effects on endothelial cells and circulating leukocytes could be reversed by neutralizing anti-TNF-α treatment. We identified alveolar macrophages as the primary source of elevated cytokine production after PM exposure. Accordingly, in vivo depletion of alveolar macrophages by intranasal clodronate attenuated inflammation and cell recruitment to infarcted tissue of ROFA-exposed mice. Taken together, our data demonstrate that exposure to environmental PM induces the release of inflammatory cytokines from alveolar macrophages which directly worsens the course of MI in mice. These findings uncover a novel link between air pollution PM exposure and inflammatory pathways, highlighting the importance of environmental factors in cardiovascular disease.Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Wolf, Dennis. University Of Freiburg; AlemaniaFil: Anto Michel, Nathaly. University Of Freiburg; AlemaniaFil: Mauler, Maximilian. University Of Freiburg; AlemaniaFil: Dufner, Bianca. University Of Freiburg; AlemaniaFil: Hoppe, Natalie. University Of Freiburg; AlemaniaFil: Beckert, Jessica. University Of Freiburg; AlemaniaFil: Jäekel, Markus. University Of Freiburg; AlemaniaFil: Magnani, Natalia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Duerschmied, Daniel. University Of Freiburg; AlemaniaFil: Tasat, Deborah Ruth. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; ArgentinaFil: Alvarez, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Reinöhl, Jochen. University Of Freiburg; AlemaniaFil: von zur Muhlen, Constantin. University Of Freiburg; AlemaniaFil: Idzko, Marco. University Of Freiburg; AlemaniaFil: Bode, Christoph. University Of Freiburg; AlemaniaFil: Hilgendorf, Ingo. University Of Freiburg; AlemaniaFil: Evelson, Pablo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Zirlik, Andreas. University Of Freiburg; Alemani

Bureaucracy as a Lens for Analyzing and Designing Algorithmic Systems

Scholarship on algorithms has drawn on the analogy between algorithmic systems and bureaucracies to diagnose shortcomings in algorithmic decision-making. We extend the analogy further by drawing on Michel Crozier’s theory of bureaucratic organizations to analyze the relationship between algorithmic and human decision-making power. We present algorithms as analogous to impartial bureaucratic rules for controlling action, and argue that discretionary decision-making power in algorithmic systems accumulates at locations where uncertainty about the operation of algorithms persists. This key point of our essay connects with Alkhatib and Bernstein’s theory of ’street-level algorithms’, and highlights that the role of human discretion in algorithmic systems is to accommodate uncertain situations which inflexible algorithms cannot handle. We conclude by discussing how the analysis and design of algorithmic systems could seek to identify and cultivate important sources of uncertainty, to enable the human discretionary work that enhances systemic resilience in the face of algorithmic errors.Peer reviewe

Molecular modelling of the GIR1 branching ribozyme gives new insight into evolution of structurally related ribozymes

Twin-ribozyme introns contain a branching ribozyme (GIR1) followed by a homing endonuclease (HE) encoding sequence embedded in a peripheral domain of a group I splicing ribozyme (GIR2). GIR1 catalyses the formation of a lariat with 3 nt in the loop, which caps the HE mRNA. GIR1 is structurally related to group I ribozymes raising the question about how two closely related ribozymes can carry out very different reactions. Modelling of GIR1 based on new biochemical and mutational data shows an extended substrate domain containing a GoU pair distinct from the nucleophilic residue that dock onto a catalytic core showing a different topology from that of group I ribozymes. The differences include a core J8/7 region that has been reduced and is complemented by residues from the pre-lariat fold. These findings provide the basis for an evolutionary mechanism that accounts for the change from group I splicing ribozyme to the branching GIR1 architecture. Such an evolutionary mechanism can be applied to other large RNAs such as the ribonuclease P

Rôle du scutellum dans l’obtention de plantes néoformées in vitro chez le maïs

Les expériences décrites ont visé à mieux connaître les aptitudes à la régénération chez le maïs (Zea mays L.) à partir de scutellums de jeunes embryons. Pour deux critères, le pourcentage de régénération et la productivité en jeunes plantes, les rôles respectifs de l’embryon et de la plante mère support des explants sont discutés.Regeneration from the scutellum of young maize embryos of inbred genotype A 188 was studied. The relative importance of the embryo and mother plant is discussed for two criteria, the percentage of regenerating siacutel and their productivity (number of young plantlets which can be potted up following regeneration from calluses obtained from one or a class of scutella). We did not find any « mother plant » effect on the probability of regeneration from the scutellum but we showed a strong « mother plant » effect on the productivity of embryos in a particular length class

Rôle du scutellum dans l'obtention de plantes néoformées in vitro chez le maïs

Les expériences décrites ont visé à mieux connaître les aptitudes à la régénération chez le maïs (Zea mays L.) à partir de scutellums de jeunes embryons. Pour deux critères, le pourcentage de régénération et la productivité en jeunes plantes, les rôles respectifs de l'embryon et de la plante mère support des explants sont discutés