Pulsed Feedback Defers Cellular Differentiation

Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable “polyphasic” positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a “timer” that operates over timescales much longer than a cell cycle

Star forming dwarf galaxies

Star forming dwarf galaxies (SFDGs) have a high gas content and low metallicities, reminiscent of the basic entities in hierarchical galaxy formation scenarios. In the young universe they probably also played a major role in the cosmic reionization. Their abundant presence in the local volume and their youthful character make them ideal objects for detailed studies of the initial stellar mass function (IMF), fundamental star formation processes and its feedback to the interstellar medium. Occasionally we witness SFDGs involved in extreme starbursts, giving rise to strongly elevated production of super star clusters and global superwinds, mechanisms yet to be explored in more detail. SFDGs is the initial state of all dwarf galaxies and the relation to the environment provides us with a key to how different types of dwarf galaxies are emerging. In this review we will put the emphasis on the exotic starburst phase, as it seems less important for present day galaxy evolution but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres

Speckle Interferometry of Nearby Multiple Stars. IV. Measurements in 2004 and New Orbits

The results of speckle interferometric observations of 104 binary and 6 triple stars performed at the BTA 6 m telescope in 2004 October are presented. Nearby low-mass stars are mostly observed for the program, among which 59 there are new binaries recently discovered by the Hipparcos astrometric satellite. Concurrently with the diffraction-limited position measurements we obtained 154 brightness ratio measurements of binary and multiple star components in different bands of the visible spectrum. New, first-resolved binaries are the symbiotic star CH Cyg with a weak companion at 0.043'' separation and the pair of red dwarfs, GJ 913 = HIP 118212. In addition, we derived the orbital parameters for two interferometric systems: the CN-giant pair HD 210211 = HIP 109281 (P=10.7 yr) and the G2V-K2V binary GJ 9830 = HIP 116259 (P=15.7 yr).Comment: 11 pages, 2 figures, accepted to Astrophysical Bulleti

The role of thermal energy accommodation and atomic recombination probabilities in low pressure oxygen plasmas

International audienceSurface interaction probabilities are critical parameters that determine the behaviour of low pressure plasmas and so are crucial input parameters for plasma simulations that play a key role in determining their accuracy. However, these parameters are difficult to estimate without in situ measurements. In this work, the role of two prominent surface interaction probabilities, the atomic oxygen recombination coefficient ? O and the thermal energy accommodation coefficient ? E in determining the plasma properties of low pressure inductively coupled oxygen plasmas are investigated using two-dimensional fluid-kinetic simulations. These plasmas are the type used for semiconductor processing. It was found that ? E plays a crucial role in determining the neutral gas temperature and neutral gas density. Through this dependency, the value of ? E also determines a range of other plasma properties such as the atomic oxygen density, the plasma potential, the electron temperature, and ion bombardment energy and neutral-to-ion flux ratio at the wafer holder. The main role of ? O is in determining the atomic oxygen density and flux to the wafer holder along with the neutral-to-ion flux ratio. It was found that the plasma properties are most sensitive to each coefficient when the value of the coefficient is small causing the losses of atomic oxygen and thermal energy to be surface interaction limited rather than transport limited

3D Bioprinted Human Skeletal Muscle Constructs for Muscle Function Restoration

A bioengineered skeletal muscle tissue as an alternative for autologous tissue flaps, which mimics the structural and functional characteristics of the native tissue, is needed for reconstructive surgery. Rapid progress in the cell-based tissue engineering principle has enabled in vitro creation of cellularized muscle-like constructs; however, the current fabrication methods are still limited to build a three-dimensional (3D) muscle construct with a highly viable, organized cellular structure with the potential for a future human trial. Here, we applied 3D bioprinting strategy to fabricate an implantable, bioengineered skeletal muscle tissue composed of human primary muscle progenitor cells (hMPCs). The bioprinted skeletal muscle tissue showed a highly organized multi-layered muscle bundle made by viable, densely packed, and aligned myofiber-like structures. Our in vivo study presented that the bioprinted muscle constructs reached 82% of functional recovery in a rodent model of tibialis anterior (TA) muscle defect at 8 weeks of post-implantation. In addition, histological and immunohistological examinations indicated that the bioprinted muscle constructs were well integrated with host vascular and neural networks. We demonstrated the potential of the use of the 3D bioprinted skeletal muscle with a spatially organized structure that can reconstruct the extensive muscle defects

Target Site Recognition by a Diversity-Generating Retroelement

Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that are widely distributed in bacterial, phage, and plasmid genomes. They function to introduce vast amounts of targeted diversity into protein-encoding DNA sequences via mutagenic homing. Adenine residues are converted to random nucleotides in a retrotransposition process from a donor template repeat (TR) to a recipient variable repeat (VR). Using the Bordetella bacteriophage BPP-1 element as a prototype, we have characterized requirements for DGR target site function. Although sequences upstream of VR are dispensable, a 24 bp sequence immediately downstream of VR, which contains short inverted repeats, is required for efficient retrohoming. The inverted repeats form a hairpin or cruciform structure and mutational analysis demonstrated that, while the structure of the stem is important, its sequence can vary. In contrast, the loop has a sequence-dependent function. Structure-specific nuclease digestion confirmed the existence of a DNA hairpin/cruciform, and marker coconversion assays demonstrated that it influences the efficiency, but not the site of cDNA integration. Comparisons with other phage DGRs suggested that similar structures are a conserved feature of target sequences. Using a kanamycin resistance determinant as a reporter, we found that transplantation of the IMH and hairpin/cruciform-forming region was sufficient to target the DGR diversification machinery to a heterologous gene. In addition to furthering our understanding of DGR retrohoming, our results suggest that DGRs may provide unique tools for directed protein evolution via in vivo DNA diversification

Asymmetric Kelvin-Helmholtz Instability at Jupiter's Magnetopause Boundary: Implications for Corotation-Dominated Systems

©2018. American Geophysical Union. The multifluid Lyon-Fedder-Mobarry (MFLFM) global magnetosphere model is used to study the interactions between solar wind and rapidly rotating, internally driven Jupiter magnetosphere. The MFLFM model is the first global simulation of Jupiter magnetosphere that captures the Kelvin-Helmholtz instability (KHI) in the critically important subsolar region. Observations indicate that Kelvin-Helmholtz vortices are found predominantly in the dusk sector. Our simulations explain that this distribution is driven by the growth of KHI modes in the prenoon and subsolar region (e.g., > 10 local time) that are advected by magnetospheric flows to the dusk sector. The period of density fluctuations at the dusk terminator flank (18 magnetic local time, MLT) is roughly 1.4 h compared with 7.2 h at the dawn flank (6 MLT). Although the simulations are only performed using parameters of the Jupiter's magnetosphere, the results may also have implications for solar wind-magnetosphere interactions at other corotation-dominated systems such as Saturn. For instance, the simulated average azimuthal speed of magnetosheath flows exhibit significant dawn-dusk asymmetry, consistent with recent observations at Saturn. The results are particularly relevant for the ongoing Juno mission and the analysis of dawnside magnetopause boundary crossings for other planetary missions.Link_to_subscribed_fulltex