30 research outputs found
Geometry of Schroedinger Space-Times II: Particle and Field Probes of the Causal Structure
We continue our study of the global properties of the z=2 Schroedinger
space-time. In particular, we provide a codimension 2 isometric embedding which
naturally gives rise to the previously introduced global coordinates.
Furthermore, we study the causal structure by probing the space-time with point
particles as well as with scalar fields. We show that, even though there is no
global time function in the technical sense (Schroedinger space-time being
non-distinguishing), the time coordinate of the global Schroedinger coordinate
system is, in a precise way, the closest one can get to having such a time
function. In spite of this and the corresponding strongly Galilean and almost
pathological causal structure of this space-time, it is nevertheless possible
to define a Hilbert space of normalisable scalar modes with a well-defined
time-evolution. We also discuss how the Galilean causal structure is reflected
and encoded in the scalar Wightman functions and the bulk-to-bulk propagator.Comment: 32 page
Effectiveness of an implementation optimisation intervention aimed at increasing parent engagement in HENRY, a childhood obesity prevention programme - the Optimising Family Engagement in HENRY (OFTEN) trial: study protocol for a randomised controlled trial
Background: Family-based interventions to prevent childhood obesity depend upon parents’ taking action to improve diet and other lifestyle behaviours in their families. Programmes that attract and retain high numbers of parents provide an enhanced opportunity to improve public health and are also likely to be more cost-effective than those that do not. We have developed a theory-informed optimisation intervention to promote parent engagement within an existing childhood obesity prevention group programme, HENRY (Health Exercise Nutrition for the Really Young). Here, we describe a proposal to evaluate the effectiveness of this optimisation intervention in regard to the engagement of parents and cost-effectiveness. Methods/design: The Optimising Family Engagement in HENRY (OFTEN) trial is a cluster randomised controlled trial being conducted across 24 local authorities (approximately 144 children’s centres) which currently deliver HENRY programmes. The primary outcome will be parental enrolment and attendance at the HENRY programme, assessed using routinely collected process data. Cost-effectiveness will be presented in terms of primary outcomes using acceptability curves and through eliciting the willingness to pay for the optimisation from HENRY commissioners. Secondary outcomes include the longitudinal impact of the optimisation, parent-reported infant intake of fruits and vegetables (as a proxy to compliance) and other parent-reported family habits and lifestyle. Discussion: This innovative trial will provide evidence on the implementation of a theory-informed optimisation intervention to promote parent engagement in HENRY, a community-based childhood obesity prevention programme. The findings will be generalisable to other interventions delivered to parents in other community-based environments. This research meets the expressed needs of commissioners, children’s centres and parents to optimise the potential impact that HENRY has on obesity prevention. A subsequent cluster randomised controlled pilot trial is planned to determine the practicality of undertaking a definitive trial to robustly evaluate the effectiveness and cost-effectiveness of the optimised intervention on childhood obesity prevention
The F0F1-ATP Synthase Complex Contains Novel Subunits and Is Essential for Procyclic Trypanosoma brucei
The mitochondrial F0F1 ATP synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little is known about its composition and role in Trypanosoma brucei, an early diverged eukaryotic pathogen. We purified the F0F1 ATP synthase by a combination of affinity purification, immunoprecipitation and blue-native gel electrophoresis and characterized its composition and function. We identified 22 proteins of which five are related to F1 subunits, three to F0 subunits, and 14 which have no obvious homology to proteins outside the kinetoplastids. RNAi silencing of expression of the F1 α subunit or either of the two novel proteins showed that they are each essential for the viability of procyclic (insect stage) cells and are important for the structural integrity of the F0F1-ATP synthase complex. We also observed a dramatic decrease in ATP production by oxidative phosphorylation after silencing expression of each of these proteins while substrate phosphorylation was not severely affected. Our procyclic T. brucei cells were sensitive to the ATP synthase inhibitor oligomycin even in the presence of glucose contrary to earlier reports. Hence, the two novel proteins appear essential for the structural organization of the functional complex and regulation of mitochondrial energy generation in these organisms is more complicated than previously thought
Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves
Nerve impulses are propagated at nodes of Ranvier in the
myelinated nerves of vertebrates. Internodal distances have
been proposed to affect the velocity of nerve impulse conduction;
however, direct evidence is lacking, and the cellular mechanisms
that might regulate the length of the myelinated segments
are unknown. Ramon y Cajal described longitudinal and transverse
bands of cytoplasm or trabeculae in internodal Schwann
cells and suggested that they had a nutritive function. Here we
show that internodal growth in wild-type nerves is precisely
matched to nerve extension, but disruption of the cytoplasmic
bands in Periaxin-null mice impairs Schwann cell elongation during nerve growth. By contrast, myelination proceeds normally.
The capacity of wild-type and mutant Schwann cells to
elongate is cell-autonomous, indicating that passive stretching
can account for the lengthening of the internode during limb
growth. As predicted on theoretical grounds, decreased internodal
distances strikingly decrease conduction velocities and so
affect motor function.We propose that microtubule-based transport
in the longitudinal bands of Cajal permits internodal
Schwann cells to lengthen in response to axonal growth, thus
ensuring rapid nerve impulse transmission
Structure of the c(10) ring of the yeast mitochondrial ATP synthase in the open conformation
The proton pore of the F1Fo ATP synthase consists of a ring of c subunits, which rotates, driven by downhill proton diffusion across the membrane. An essential carboxylate side chain in each subunit provides a proton-binding site. In all the structures of c-rings reported to date, these sites are in a closed, ion-locked state. Structures are here presented of the c10 ring from Saccharomyces cerevisiae determined at pH 8.3, 6.1 and 5.5, at resolutions of 2.0 Ã…, 2.5 Ã… and 2.0 Ã…, respectively. The overall structure of this mitochondrial c-ring is similar to known homologs, except that the essential carboxylate, Glu59, adopts an open extended conformation. Molecular dynamics simulations reveal that opening of the essential carboxylate is a consequence of the amphiphilic nature of the crystallization buffer. We propose that this new structure represents the functionally open form of the c subunit, which facilitates proton loading and release
A role for the two-helix finger of the SecA ATPase in protein translocation
An important step in the biosynthesis of many proteins is their partial or complete translocation across the plasma membrane in prokaryotes or the endoplasmic reticulum membrane in eukaryotes1. In bacteria, secretory proteins are generally translocated after completion of their synthesis by the interaction of the cytoplasmic ATPase SecA and a protein-conducting channel formed by the SecY complex2. How SecA moves substrates through the SecY channel is unclear. However, a recent structure of a SecA–SecY complex raises the possibility that the polypeptide chain is moved by a two-helix finger domain of SecA that is inserted into the cytoplasmic opening of the SecY channel3. Here we have used disulphide-bridge crosslinking to show that the loop at the tip of the two-helix finger of Escherichia coli SecA interacts with a polypeptide chain right at the entrance into the SecY pore. Mutagenesis demonstrates that a tyrosine in the loop is particularly important for translocation, but can be replaced by some other bulky, hydrophobic residues. We propose that the two-helix finger of SecA moves a polypeptide chain into the SecY channel with the tyrosine providing the major contact with the substrate, a mechanism analogous to that suggested for hexameric, protein-translocating ATPases