Complete genome sequence of the hemotrophic Mycoplasma suis strain KI3806

Mycoplasma suis, a member of the hemotrophic mycoplasma (HM) group, parasitize erythrocytes of pigs. Increasing evidence suggests that M. suis is also a zoonotic agent. Highly pathogenic strains of M. suis (e.g., M. suis KI3806) have been demonstrated to invade erythrocytes. This complete sequenced and manually annotated genome of M. suis KI3806 is the first available from this species and from the HM group. The DNA was isolated from blood samples of experimentally infected pigs due to the lack of an in vitro cultivation system. The small circular chromosome of 709,270 bp, encoding an unexpectedly high number of hypothetical proteins and limited transport and metabolic capacities, could reflect the unique lifestyle of HM on the surface of erythrocytes

Dependability engineering of silent self-stabilizing systems

Abstract. Self-stabilization is an elegant way of realizing non-masking fault-tolerant systems. Sustained research over last decades has produced multiple self-stabilizing algorithms for many problems in distributed computing. In this paper, we present a framework to evaluate multiple selfstabilizing solutions under a fault model that allows intermittent transient faults. To that end, metrics to quantify the dependability of selfstabilizing systems are defined. It is also shown how to derive models that are suitable for probabilistic model checking in order to determine those dependability metrics. A heuristics-based method is presented to analyze counterexamples returned by a probabilistic model checker in case the system under investigation does not exhibit the desired degree of dependability. Based on the analysis, the self-stabilizing algorithm is subsequently refined.

Proving stabilization of biological systems

Abstract. We describe an efficient procedure for proving stabilization of biological systems modeled as qualitative networks or genetic regulatory networks. For scalability, our procedure uses modular proof techniques, where state-space exploration is applied only locally to small pieces of the system rather than the entire system as a whole. Our procedure exploits the observation that, in practice, the form of modular proofs can be restricted to a very limited set. For completeness, our technique falls back on a non-compositional counterexample search. Using our new procedure, we have solved a number of challenging published examples, including: a 3-D model of the mammalian epidermis; a model of metabolic networks operating in type-2 diabetes; a model of fate determination of vulval precursor cells in the C. elegans worm; and a model of pair-rule regulation during segmentation in the Drosophila embryo. Our results show many orders of magnitude speedup in cases where previous stabilization proving techniques were known to succeed, and new results in cases where tools had previously failed.

Hemotrophic mycoplasmas induce programmed cell death in red blood cells

Hemotrophic mycoplasmas (HM) are uncultivable bacteria found on and in the red blood cells (RBCs). The main clinical sign of HM infections is the hemolytic anemia. However, anemia-inducing pathogenesis has not been totally clarified. In this work we used the splenectomized pig as animal model and Mycoplasma suis as a representative for hemotrophic mycoplasmas to study anemia pathogenesis. Eryptosis, i.e. programmed cell death of RBCs, is characterized by cell shrinkage, microvesiculation and phosphatidylserine (PS) exposure on the outer membrane. The eryptosis occurrence and its influence on anemia pathogenesis was observed over the time-course of M. suis infections in pigs using 3 M. suis isolates of differing virulence. All 3 isolates induced eryptosis, but with different characteristics. The occurrence of eryptosis could as well be confirmed in vitro: serum and plasma of an acutely ill pig induced PS exposure on erythrocytes drawn from healthy pigs. Since M. suis is able to induce eryptotic processes it is concluded that eryptosis is one anemia-inducing factor during M. suis infections and, therefore, plays a significant role in the pathogenesis of infectious anemia due to HM infection