Antigenic variation in <i>Trypanosoma brucei</i>: joining the DOTs

African trypanosomes, such as &lt;i&gt;Trypanosoma brucei&lt;/i&gt;, are protistan parasites that cause sleeping sickness. Though first described more than a century ago, trypanosomes remain a blight on the health of the human population and on the economy of sub-Saharan Africa. &lt;i&gt;T. brucei&lt;/i&gt; replicates in the bloodstream of infected mammals and traverses the blood-brain barrier to enter the central nervous system in the late, frequently fatal, stages of the disease. Because of its extracellular lifestyle, &lt;i&gt;T. brucei&lt;/i&gt; is continuously exposed to antibody challenge. To circumvent this, the parasite uses antigenic variation of a surface protein named the variant surface glycoprotein (VSG). Around 107 VSG molecules are expressed on the parasite's cell surface, creating a dense coat that prevents adaptive immunity from detecting or accessing invariant antigens. However, antibodies against the expressed VSG are generated, and periodic switches to an immunologically distinct VSG coat are necessary for parasite survival. Such switches are pre-emptive of the immune response and contribute to the pattern of trypanosome growth seen in an infected host (Figure 1): parasite numbers increase, but then drop as VSG-specific antibodies are raised by the host. Cells that have switched to another VSG coat survive this killing and seed the outgrowth of a subsequent peak of parasites, which is again decimated by anti-VSG immune killing. As a survival strategy, antigenic variation succeeds by prolonging the time that the parasite

Contributions of Histone H3 Nucleosome Core Surface Mutations to Chromatin Structures, Silencing and DNA Repair

Histone H3 mutations in residues that cluster in a discrete region on the nucleosome surface around lysine 79 of H3 affect H3-K79 methylation, impair transcriptional silencing in subtelomeric chromatin, and reveal distinct contributions of histone H3 to various DNA-damage response and repair pathways. These residues might act by recruitment of silencing and DNA-damage response factors. Alternatively, their location on the nucleosome surface suggests a possible involvement in nucleosome positioning, stability and nucleosome interactions. Here, we show that the yeast H3 mutants hht2-T80A, hht2-K79E, hht2-L70S, and hht2-E73D show normal nucleosome positioning and stability in minichromosomes. However, loss of silencing in a subtelomeric URA3 gene correlates with a shift of the promoter nucleosome, while nucleosome positions and stability in the coding region are maintained. Moreover, the H3 mutants show normal repair of UV lesions by photolyase and nucleotide excision repair in minichromosomes and slightly enhanced repair in the subtelomeric region. Thus, these results support a role of those residues in the recruitment of silencing proteins and argue against a general role in nucleosome organization

Genome-Wide Analysis of Factors Affecting Transcription Elongation and DNA Repair: A New Role for PAF and Ccr4-Not in Transcription-Coupled Repair

RNA polymerases frequently deal with a number of obstacles during transcription elongation that need to be removed for transcription resumption. One important type of hindrance consists of DNA lesions, which are removed by transcription-coupled repair (TC-NER), a specific sub-pathway of nucleotide excision repair. To improve our knowledge of transcription elongation and its coupling to TC-NER, we used the yeast library of non-essential knock-out mutations to screen for genes conferring resistance to the transcription-elongation inhibitor mycophenolic acid and the DNA-damaging agent 4-nitroquinoline-N-oxide. Our data provide evidence that subunits of the SAGA and Ccr4-Not complexes, Mediator, Bre1, Bur2, and Fun12 affect transcription elongation to different extents. Given the dependency of TC-NER on RNA Polymerase II transcription and the fact that the few proteins known to be involved in TC-NER are related to transcription, we performed an in-depth TC-NER analysis of a selection of mutants. We found that mutants of the PAF and Ccr4-Not complexes are impaired in TC-NER. This study provides evidence that PAF and Ccr4-Not are required for efficient TC-NER in yeast, unraveling a novel function for these transcription complexes and opening new perspectives for the understanding of TC-NER and its functional interconnection with transcription elongation

Modeling Performance Measurement of Mobile Manipulators

Mobile manipulators are being marketed around the world as single manufacturer systems (i.e., robot arm and vehicle manufactured by the same organization) and as independent robot arms, from a different manufacturer and integrated with automatic guided vehicles (AGVs) or mobile robots. Test methods for measuring safety and performance of either of these types of mobile manipulators have yet to be developed and therefore, potential users cannot compare one system to another to match to tasks. Similarly, the control of these systems can vary greatly from AGV control to more autonomous mobile robot control and further, to robot arm control methods. Systems Modeling Language (SysML) is a general-purpose modeling language for systems engineering applications that supports the specification, analysis, design, verification, and validation of simple through complex systems, such as mobile manipulators. This paper uses SysML to describe a method using an artifact for performance measurement of mobile manipulators performing assembly tasks. Uncertainty propagation, a key component in understanding the effects of mobile manipulator constraints, is also modeled and described. ? 2017 IEEE.IEEE Robotics and Automation Societ

Obstacle Detection using a TOF Range Camera for Indoor AGV Navigation

ABSTRACT — The performance evaluation of an obstacle detection and segmentation algorithm for Automated Guided Vehicle (AGV) navigation in factory-like environments using a 3D real-time range camera is the subject of this paper 1. Our approach has been tested successfully on British safety standard recommended object sizes and materials placed on the vehicle path. The segmented (mapped) obstacles are then verified using absolute measurements obtained using a relatively accurate 2D scanning laser rangefinder. Keywords: Automated Guided Vehicle, 3D range camera, 2