Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate

Type 1 pili are the archetypal representative of a widespread class of adhesive multisubunit fibres in Gram-negative bacteria. During pilus assembly, subunits dock as chaperone-bound complexes to an usher, which catalyses their polymerization and mediates pilus translocation across the outer membrane. Here we report the crystal structure of the full-length FimD usher bound to the FimC-FimH chaperone-adhesin complex and that of the unbound form of the FimD translocation domain. The FimD-FimC-FimH structure shows FimH inserted inside the FimD 24-stranded β-barrel translocation channel. FimC-FimH is held in place through interactions with the two carboxy-terminal periplasmic domains of FimD, a binding mode confirmed in solution by electron paramagnetic resonance spectroscopy. To accommodate FimH, the usher plug domain is displaced from the barrel lumen to the periplasm, concomitant with a marked conformational change in the β-barrel. The amino-terminal domain of FimD is observed in an ideal position to catalyse incorporation of a newly recruited chaperone-subunit complex. The FimD-FimC-FimH structure provides unique insights into the pilus subunit incorporation cycle, and captures the first view of a protein transporter in the act of secreting its cognate substrate.     

Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking

The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours, but our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural-circuit elements of this pathway selectively during behaviour. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibres from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. Here we show that optical stimulation of the pathway from the BLA to the NAc in mice reinforces behavioural responding to earn additional optical stimulation of these synaptic inputs. Optical stimulation of these glutamatergic fibres required intra-NAc dopamine D1-type receptor signalling, but not D2-type receptor signalling. Brief optical inhibition of fibres from the BLA to the NAc reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behaviour. Moreover, although optical stimulation of glutamatergic fibres from the medial prefrontal cortex to the NAc also elicited reliable excitatory synaptic responses, optical self-stimulation behaviour was not observed by activation of this pathway. These data indicate that whereas the BLA is important for processing both positive and negative affect, the glutamatergic pathway from the BLA to the NAc, in conjunction with dopamine signalling in the NAc, promotes motivated behavioural responding. Thus, optogenetic manipulation of anatomically distinct synaptic inputs to the NAc reveals functionally distinct properties of these inputs in controlling reward-seeking behaviours.     

Real-time quantum feedback prepares and stabilizes photon number states

Feedback loops are central to most classical control procedures. A controller compares the signal measured by a sensor (system output) with the target value or set-point. It then adjusts an actuator (system input) to stabilize the signal around the target value. Generalizing this scheme to stabilize a micro-system's quantum state relies on quantum feedback, which must overcome a fundamental difficulty: the sensor measurements cause a random back-action on the system. An optimal compromise uses weak measurements, providing partial information with minimal perturbation. The controller should include the effect of this perturbation in the computation of the actuator's operation, which brings the incrementally perturbed state closer to the target. Although some aspects of this scenario have been experimentally demonstrated for the control of quantum or classical micro-system variables, continuous feedback loop operations that permanently stabilize quantum systems around a target state have not yet been realized. Here we have implemented such a real-time stabilizing quantum feedback scheme following a method inspired by ref. 13. It prepares on demand photon number states (Fock states) of a microwave field in a superconducting cavity, and subsequently reverses the effects of decoherence-induced field quantum jumps. The sensor is a beam of atoms crossing the cavity, which repeatedly performs weak quantum non-demolition measurements of the photon number. The controller is implemented in a real-time computer commanding the actuator, which injects adjusted small classical fields into the cavity between measurements. The microwave field is a quantum oscillator usable as a quantum memory or as a quantum bus swapping information between atoms. Our experiment demonstrates that active control can generate non-classical states of this oscillator and combat their decoherence, and is a significant step towards the implementation of complex quantum information operations.     

Flood frequency and the assemblage of dispersal types in hanging gardens of the Narrows, Zion National Park, Utah

Hanging gardens of the Narrows, Zion National Park, Utah, are plant communities growing at permanent seeps on the canyon walls. The gardens are isolated from each other and from other plant communities by vertical expanses of sandstone. Gardens consist mostly of herbaceous species less than 1 m tall. Though not individually species-rich, the hanging gardens are diverse as a group, and very dissimilar. This study considers two explanations of the heterogeneous distribution of species in hanging gardens. The assemblages of dispersal types in gardens of different spatial attributes and disturbance frequencies are examined. The G H statistic, a log likelihood ratio test, analyzes the incidence of dispersal types among classes of three spatial and two disturbance variables. The disturbance variables of expected flood frequency and soil depth segregate dispersal types; and the spatial variables of area, distance to possible seed sources, and relative isolation do not. Ferns and mosses, dispersing through spores, dominate a heterogeneous fugitive guild in the flood-prone gardens. Infrequently flooded gardens support more large-seeded species.     

Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts

Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts, but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Here we use a guinea-pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo, we transplanted hESC-CMs expressing the genetically encoded calcium sensor, GCaMP3 (refs 4, 5). By correlating the GCaMP3 fluorescent signal with the host ECG, we found that grafts in uninjured hearts have consistent 1:1 host–graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. Thus, human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair.     

Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition

Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.