High-Resolution Phenotypic Profiling Defines Genes Essential for Mycobacterial Growth and Cholesterol Catabolism

The pathways that comprise cellular metabolism are highly interconnected, and alterations in individual enzymes can have far-reaching effects. As a result, global profiling methods that measure gene expression are of limited value in predicting how the loss of an individual function will affect the cell. In this work, we employed a new method of global phenotypic profiling to directly define the genes required for the growth of Mycobacterium tuberculosis. A combination of high-density mutagenesis and deep-sequencing was used to characterize the composition of complex mutant libraries exposed to different conditions. This allowed the unambiguous identification of the genes that are essential for Mtb to grow in vitro, and proved to be a significant improvement over previous approaches. To further explore functions that are required for persistence in the host, we defined the pathways necessary for the utilization of cholesterol, a critical carbon source during infection. Few of the genes we identified had previously been implicated in this adaptation by transcriptional profiling, and only a fraction were encoded in the chromosomal region known to encode sterol catabolic functions. These genes comprise an unexpectedly large percentage of those previously shown to be required for bacterial growth in mouse tissue. Thus, this single nutritional change accounts for a significant fraction of the adaption to the host. This work provides the most comprehensive genetic characterization of a sterol catabolic pathway to date, suggests putative roles for uncharacterized virulence genes, and precisely maps genes encoding potential drug targets

The effect of normal load force and roughness on the dynamic traction developed at the shoe-surface interface in tennis

During tennis-specific movements, such as accelerating and side stepping, the dynamic traction provided by the shoe-surface combination plays an important role in the injury risk and performance of the player. Acrylic hard court tennis surfaces have been reported to have increased injury occurrence, partly caused by increased traction that developed at the shoe-surface interface. Often mechanical test methods used for the testing and categorisation of playing surfaces do not tend to simulate loads occurring during participation on the surface, and thus are unlikely to predict the human response to the surface. A traction testing device, discussed in this paper, has been used to mechanically measure the dynamic traction force between the shoe and the surface under a range of normal loading conditions that are relevant to real-life play. Acrylic hard court tennis surfaces generally have a rough surface topography, due to their sand and acrylic paint mixed top coating. Surface micro-roughness will influence the friction mechanisms present during viscoelastic contacts, as found in footwear-surface interactions. This paper aims to further understand the influence micro-roughness and normal force has on the dynamic traction that develops at the shoe-surface interface on acrylic hard court tennis surfaces. The micro-roughness and traction of a controlled set of acrylic hard court tennis surfaces have been measured. The relationships between micro-roughness, normal force, and traction force are discussed. © 2013 The Author(s)

Long-term droughts may drive drier tropical forests towards increased functional, taxonomic and phylogenetic homogeneity

Tropical ecosystems adapted to high water availability may be highly impacted by climatic changes that increase soil and atmospheric moisture deficits. Many tropical regions are experiencing significant changes in climatic conditions, which may induce strong shifts in taxonomic, functional and phylogenetic diversity of forest communities. However, it remains unclear if and to what extent tropical forests are shifting in these facets of diversity along climatic gradients in response to climate change. Here, we show that changes in climate affected all three facets of diversity in West Africa in recent decades. Taxonomic and functional diversity increased in wetter forests but tended to decrease in forests with drier climate. Phylogenetic diversity showed a large decrease along a wet-dry climatic gradient. Notably, we find that all three facets of diversity tended to be higher in wetter forests. Drier forests showed functional, taxonomic and phylogenetic homogenization. Understanding how different facets of diversity respond to a changing environment across climatic gradients is essential for effective long-term conservation of tropical forest ecosystems