Brain Oxygenation and Metabolism during Repetitive Apnea with Resuscitation of 21% and 100% Oxygen in Newborn Piglets

The oxygen distribution in the microcirculation of the piglet’s brain and striatal extracellular dopamine were determined during repetitive apnea and resuscitation with 21% or 100% oxygen. Pre-apnea cortical oxygen was 49.5 ± 10.4 mm Hg and during each apnea decreased to 8 ± 0.9 mm Hg. After ten apneic episodes followed by resuscitation with 21% or 100% oxygen, 7.48 ± 1.6% or 2.6 ± 0.5% of the tissue volume was below 10 mm Hg, respectively. Extracellular dopamine increased progressively with an increase in the number of apneas with resuscitation of 21% oxygen and at the end of ten apneic episodes it was up to 59,500 ± 11,320% of control. There was no increase in extracellular dopamine during apnea resuscitated with 100% oxygen. Repetitive apnea caused progressive increase in fraction of hypoxic brain tissue in newborn. The magnitude of the increase is dependent on whether the animals were resuscitated with room air or 100% oxygen.     

Three-dimensional structure of a macromolecular assembly that regulates type III secretion in Yersinia pestis

Yersinia pestis, the causative agent of plague, utilizes a type III secretion system (T3SS) to inject effector proteins directly into the cytosol of mammalian cells where they interfere with signal transduction pathways that regulate actin cytoskeleton dynamics and inflammation, thereby enabling the bacterium to avoid engulfment and destruction by macrophages. Type III secretion normally does not occur in the absence of close contact with eukaryotic cells. Negative regulation is mediated in part by a multiprotein complex that has been proposed to act as a physical impediment to type III secretion by blocking the entrance to the secretion apparatus prior to contact with mammalian cells. This complex is composed of YopN, its heterodimeric secretion chaperone SycN-YscB, and TyeA. Here, we report two crystal structures of YopN in complex with its heterodimeric secretion chaperone SycN-YscB and the co-regulatory protein TyeA, respectively. By merging these two overlapping structures, it was possible to construct a credible theoretical model of the YopN-SycN-YscB-TyeA complex. The modeled assembly features the secretion signaling elements of YopN at one end of an elongated structure and the secretion regulating TyeA binding site at the other. A patch of highly conserved residues on the surface of the C-terminal alpha-helix of TyeA may mediate its interaction with structural components of the secretion apparatus. Conserved arginine residues that reside inside a prominent cavity at the dimer interface of SycN-YscB were mutated in order to investigate whether they play a role in targeting the YopN-chaperone complex to the type III secretion apparatus. One of the mutants exhibited a phenotype that is consistent with this hypothesis.     

The effect of rate of distraction osteogenesis on structure and function of anterior digastric muscle fibers

The authors hypothesized that distraction at a rate of 3 mm/day, compared with mandibular distraction at a rate of 1 mm/day, would produce a maladaptive response in adjacent muscles of mastication. The authors further hypothesized that the maladaptive response would manifest at the single fiber level by means of increased sarcomeric heterogeneity, decreased maximum force output, and increased susceptibility to stretch-induced injury. In an ovine model, distraction osteogenesis of the right hemimandible was performed at either 1 mm/day for 21 days (n = 2) or 3 mm/day for 7 days (n = 2) to achieve a total distraction distance of 21 mm. The left hemimandibles served as controls. After a consolidation period of 2 days, the anterior digastric muscles were harvested; in six randomly selected single fibers from each muscle, maximum calcium-activated force (Po) was measured at optimal sarcomere length. The amount of damage to the sarcomeres in each fiber was assessed microscopically. To test susceptibility to contraction-induced injury, each fiber was given an activated stretch of 20 percent. Compared with control fibers and fibers distracted at 1 mm/day, maximum tetanic force (Po) was significantly lower in fibers distracted at 3 mm/day. Compared with control fibers, specific Po (Po/cross-sectional area) was lower in fibers distracted at 3 mm/day. The number of sarcomeres appearing damaged in fibers distracted at 3 mm/day was significantly higher than in control fibers or in fibers distracted at 1 mm/day. A greater deficit in Po was observed after a single activated stretch in fibers distracted at 3 mm/day than in control fibers or in fibers distracted at 1 mm/day. The authors conclude that distraction of the anterior digastric muscle in sheep at 3 mm/day produces a maladaptive response in the muscle fibers but a rate of 1 mm/day is tolerated by the muscle fibers. These data are consistent with the hypothesis that distraction of skeletal muscle at high rates results in increased heterogeneity of sarcomere lengths and that this increase in heterogeneity is the most likely potential mechanism resulting in whole muscle force deficits and in increased susceptibility to stretch-induced injury in distracted muscles.