The Secreted Acid Phosphatase Domain-Containing GRA44 from Toxoplasma gondii Is Required for c-Myc Induction in Infected Cells.

During host cell invasion, the eukaryotic pathogen Toxoplasma gondii forms a parasitophorous vacuole to safely reside within the cell, while it is partitioned from host cell defense mechanisms. From within this safe niche, parasites sabotage multiple host cell systems, including gene expression, apoptosis, and intracellular immune recognition, by secreting a large arsenal of effector proteins. Many parasite proteins studied for active host cell manipulative interactions have been kinases. The translocation of effectors from the parasitophorous vacuole into the host cell is mediated by a putative translocon complex, which includes the proteins MYR1, MYR2, and MYR3. Whether other proteins are involved in the structure or regulation of this putative translocon is not known. We have discovered that the secreted protein GRA44, which contains a putative acid phosphatase domain, interacts with members of this complex and is required for host cell effects downstream of effector secretion. We have determined that GRA44 is processed in a region with homology to sequences targeted by protozoan proteases of the secretory pathway and that both major cleavage fragments are secreted into the parasitophorous vacuole. Immunoprecipitation experiments showed that GRA44 interacts with a large number of secreted proteins, including MYR1. Importantly, conditional knockdown of GRA44 resulted in a lack of host cell c-Myc upregulation, which mimics the phenotype seen when members of the translocon complex are genetically disrupted. Thus, the putative acid phosphatase GRA44 is crucial for host cell alterations during Toxoplasma infection and is associated with the translocon complex which Toxoplasma relies upon for success as an intracellular pathogen.IMPORTANCE Approximately one-third of humans are infected with the parasite Toxoplasma gondii Toxoplasma infections can lead to severe disease in those with a compromised or suppressed immune system. Additionally, infections during pregnancy present a significant health risk to the developing fetus. Drugs that target this parasite are limited, have significant side effects, and do not target all disease stages. Thus, a thorough understanding of how the parasite propagates within a host is critical in the discovery of novel therapeutic targets. Toxoplasma replication requires that it enter the cells of the infected organism. In order to survive the environment inside a cell, Toxoplasma secretes a large repertoire of proteins, which hijack a number of important cellular functions. How these Toxoplasma proteins move from the parasite into the host cell is not well understood. Our work shows that the putative phosphatase GRA44 is part of a protein complex responsible for this process

When does cheating pay? worker reproductive parasitism in honeybees

In all societies, cooperation between members is necessary to allow the society to function smoothly. However, as the interests of individuals rarely overlap completely, all societies contain members that act selfishly at the expense of the greater entity. Thus, policing mechanisms are generally required in order to maintain cohesion within the society. In social insects, conflict between individuals and the society are often reproductive in nature. Kin selection theory predicts that in haplo-diploid, polyandrous species such as honeybees, workers should largely refrain from producing their own offspring, as the workers collectively have higher inclusive fitness if they rear the sons of their mother, the queen. However, opportunities for personal reproduction at the expense of colony-level fitness are often exploited by individual workers, a phenomenon known as worker reproductive parasitism (WRP). This has led to the evolution of worker ‘policing’, in which workers selectively destroy worker-laid eggs that would otherwise be reared at the colony’s expense. In my PhD, I have investigated WRP in both the Western honeybee Apis mellifera, and the Asian hive bee A. cerana. The major theme of my research has been to elucidate the circumstances that afford opportunities for potential reproductive parasites to evade worker policing. This research is significant, as it yields insights into the conflicting selective forces that lead to the formation of societies, the selfish behaviour of the individuals that comprise them and how this behaviour is controlled. These insights are applicable to all social species, including humans

Vapor-Liquid Equilibrium of Hydro-Treated Anthracene Oil (HAO61)

This thesis reports the equilibrium characteristics of the vapor and liquid phases of hydro-treated anthracene oil under conditions commonly used in coal liquefaction. These data should be useful in coal liquefaction studies and pro cess designs. The experiments were performed using the UND EERC\u27s Hot Charge, Time Sample, Batch Autoclave System. Samples could be taken at desired temperatures and pressures with minimal disturbance to the system. The automated system allowed samples to be taken in a consistent manner. Tests were conducted in temperature and pressure ranges of 300 to 440 °C and 2000 to 4000 psia, respectively. Sam pling intervals were 20 °C for temperature and 500 psi for pressure. Samples were analyzed to determine the fraction of the solvent present in the vapor state. The fraction of sol vent in the vapor phase increased with increasing tempera ture. This is the expected effect of temperature, since increased temperature typically increases the vapor pres sure of a solvent. The fraction of solvent in the vapor phase remained nearly constant as pressure was increased through the addition of nitrogen gas. The solvent behaved as could be expected, since changing the total pressure in this manner should have very little effect on the vapor pressure of a solvent. The percentages of light, middle, and heavy oils pres ent in the samples were also determined. The data show that the percentage of heavy oils in the liquid phase was nearly constant over the range of conditions tested. These data did not follow the expected trend for an increase in temperature and therefore vapor fraction. The liquid phase of the system would be expected to become richer in heavy oils as the vapor fraction increases, since the lighter, more volatile oils are the first to vaporize. The results suggest, instead, that thermal cracking of the heavier organics may have occurred, since an increase in the percent heavy oils in the liquid phase did not coin cide with increased vapor fraction. Additional analyses showed that for all of the autoclave runs, the mass per centage of heavy oils in the solvent decreased during test ing. This provides further evidence that cracking of the solvent occurred

Development of Knife-Edge Ridges on Ion-Bombarded Surfaces

We demonstrate in both laboratory and numerical experiments that ion bombardment of a modestly sloped surface can create knife-edge like ridges with extremely high slopes. Small pre-fabricated pits expand under ion bombardment, and the collision of two such pits creates knife-edge ridges. Both laboratory and numerical experiments show that the pit propagation speed and the precise shape of the knife edge ridges are universal, independent of initial conditions, as has been predicted theoretically. These observations suggest a novel method of fabrication in which a surface is pre-patterned so that it dynamically evolves to a desired target pattern made of knife-edge ridges.Comment: 5 pages, 4 figure

A model of meta-population dynamics for North Sea and West of Scotland cod - the dynamic consequences of natal fidelity

It is clear from a variety of data that cod (Gadus morhua) in the North Sea do not constitute a homogeneous population that will rapidly redistribute in response to local variability in exploitation. Hence, local exploitation has the potential to deplete local populations, perhaps to the extent that depensation occurs and recovery is impossible without recolonisation from other areas, with consequent loss of genetic diversity. The oceanographic, biological and behavioural processes which maintain the spatial population structures are only partly understood, and one of the key unknown factors is the extent to which codexhibit homing migrations to natal spawning areas. Here, we describe a model comprising 10 interlinked demes of cod in European waters, each representing groups of fish with a common natal origin. The spawning locations of fish in each deme are governed by a variety of rules concerning oceanographic dispersal, migration behaviour and straying. We describe numerical experiments with the model and comparisons with observations, which lead us to conclude that active homing is probably not necessary to explain some of the population structures of European cod. Separation of some sub-populations is possible through distance and oceanographic processes affecting the dispersal of eggs and larvae. However, other evidence suggests that homing may be a necessary behaviour to explain the structure of other sub-populations. Theconsequences for fisheries management of taking into account spatial population structuring are complicated. For example, recovery or recolonisation strategies require consideration not only of mortality rates in the target area for restoration, but also in the source areas for the recruits which may be far removed depending on the oceanography. The model has an inbuilt capability to address issues concerning the effects of climate change, including temperature change, on spatial patterns of recruitment, development and population structure in cod