DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia

Mammalian spermatogenesis is sustained by mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Maintenance of undifferentiated spermatogonia and spermatogenesis is dependent on tightly co-ordinated transcriptional and post-transcriptional mechanisms. The RNA helicase DDX5 is expressed by spermatogonia but roles in spermatogenesis are unexplored. Using an inducible knockout mouse model, we characterise an essential role for DDX5 in spermatogonial maintenance and show that Ddx5 is indispensable for male fertility. We demonstrate that DDX5 regulates appropriate splicing of key genes necessary for spermatogenesis. Moreover, DDX5 regulates expression of cell cycle genes in undifferentiated spermatogonia post-transcriptionally and is required for cell proliferation and survival. DDX5 can also act as a transcriptional co-activator and we demonstrate that DDX5 interacts with PLZF, a transcription factor required for germline maintenance, to co-regulate select target genes. Combined, our data reveal a critical multifunctional role for DDX5 in regulating gene expression programmes and activity of undifferentiated spermatogonia

Real-Time High Resolution 3D Imaging of the Lyme Disease Spirochete Adhering to and Escaping from the Vasculature of a Living Host

Pathogenic spirochetes are bacteria that cause a number of emerging and re-emerging diseases worldwide, including syphilis, leptospirosis, relapsing fever, and Lyme borreliosis. They navigate efficiently through dense extracellular matrix and cross the blood–brain barrier by unknown mechanisms. Due to their slender morphology, spirochetes are difficult to visualize by standard light microscopy, impeding studies of their behavior in situ. We engineered a fluorescent infectious strain of Borrelia burgdorferi, the Lyme disease pathogen, which expressed green fluorescent protein (GFP). Real-time 3D and 4D quantitative analysis of fluorescent spirochete dissemination from the microvasculature of living mice at high resolution revealed that dissemination was a multi-stage process that included transient tethering-type associations, short-term dragging interactions, and stationary adhesion. Stationary adhesions and extravasating spirochetes were most commonly observed at endothelial junctions, and translational motility of spirochetes appeared to play an integral role in transendothelial migration. To our knowledge, this is the first report of high resolution 3D and 4D visualization of dissemination of a bacterial pathogen in a living mammalian host, and provides the first direct insight into spirochete dissemination in vivo

Bistable helices.

We extend elasticity theory of filaments to encompass systems, such as bacterial flagella, that display competition between two helical structures of opposite chirality. A general, fully intrinsic formulation of the dynamics of bend and twist degrees of freedom is developed using the natural frame of space curves, spanning from the inviscid limit to the viscously overdamped regime applicable to cellular biology. Aspects of front propagation found in flagella are discussed

Large variability in the motility of spiroplasmas in media of different viscosities

Spiroplasmas are bacteria that do not possess flagella and their motility is linked to kink propagation coupled to changes in the cell body helicity. While the motility of bacteria with flagellar motion has been studied extensively, less work has been devoted to the motility of spiroplasmas. We first show that the motility of such bacteria has large variability from individual to individual as well as large fluctuations in time. The Brownian motion of such bacteria both in orientation and translation is also highlighted. We propose a simple model to disentangle the different components of this motility by examining trajectories of single bacteria in different viscosity solvents. The mean velocity of the bacteria turns out to depend on the viscosity of the medium as it increases with viscosity. Further, the temporal fluctuations of the bacteria motility turn out to be very strong with a direct link to tumbling events particular to this bacteria