Dynamic changes in the brain protein interaction network correlates with progression of Aβ42 pathology in Drosophila

Alzheimer’s disease (AD), the most prevalent form of dementia, is a progressive and devastating neurodegenerative condition for which there are no effective treatments. Understanding the molecular pathology of AD during disease progression may identify new ways to reduce neuronal damage. Here, we present a longitudinal study tracking dynamic proteomic alterations in the brains of an inducible Drosophila melanogaster model of AD expressing the Arctic mutant Aβ42 gene. We identified 3093 proteins from flies that were induced to express Aβ42 and age-matched healthy controls using label-free quantitative ion-mobility data independent analysis mass spectrometry. Of these, 228 proteins were significantly altered by Aβ42 accumulation and were enriched for AD-associated processes. Network analyses further revealed that these proteins have distinct hub and bottleneck properties in the brain protein interaction network, suggesting that several may have significant effects on brain function. Our unbiased analysis provides useful insights into the key processes governing the progression of amyloid toxicity and forms a basis for further functional analyses in model organisms and translation to mammalian systems

Direct Observation of the Superfluid Phase Transition in Ultracold Fermi Gases

Water freezes into ice, atomic spins spontaneously align in a magnet, liquid helium becomes superfluid: Phase transitions are dramatic phenomena. However, despite the drastic change in the system's behaviour, observing the transition can sometimes be subtle. The hallmark of Bose-Einstein condensation (BEC) and superfluidity in trapped, weakly interacting Bose gases is the sudden appearance of a dense central core inside a thermal cloud. In strongly interacting gases, such as the recently observed fermionic superfluids, this clear separation between the superfluid and the normal parts of the cloud is no longer given. Condensates of fermion pairs could be detected only using magnetic field sweeps into the weakly interacting regime. The quantitative description of these sweeps presents a major theoretical challenge. Here we demonstrate that the superfluid phase transition can be directly observed by sudden changes in the shape of the clouds, in complete analogy to the case of weakly interacting Bose gases. By preparing unequal mixtures of the two spin components involved in the pairing, we greatly enhance the contrast between the superfluid core and the normal component. Furthermore, the non-interacting wings of excess atoms serve as a direct and reliable thermometer. Even in the normal state, strong interactions significantly deform the density profile of the majority spin component. We show that it is these interactions which drive the normal-to-superfluid transition at the critical population imbalance of 70(5)%.Comment: 16 pages (incl. Supplemental Material), 5 figure

Finite temperature phase diagram of a polarised Fermi condensate

The two-component Fermi gas is the simplest fermion system displaying superfluidity, and as such finds applications ranging from the theory of superconductivity to QCD. Ultracold atomic gases provide an exceptionally clean realization of this system, where the interatomic interaction and the atom species population are both independent, tuneable parameters. This allows one to investigate the Fermi gas with imbalanced spin populations, which had previously been experimentally elusive, and this prospect has stimulated much theoretical activity. Here we show that the finite temperature phase diagram contains a region of phase separation between the superfluid and normal states that touches the boundary of second-order superfluid transitions at a tricritical point, reminiscent of the phase diagram of $^3$He-$^4$He mixtures. A variation of interaction strength then results in a line of tricritical points that terminates at zero temperature on the molecular Bose-Einstein condensate (BEC) side. On this basis, we argue that tricritical points will play an important role in the recent experiments on polarised atomic Fermi gases.Comment: 6 pages, 4 figures. Manuscript extended and figures modified. For final version, see Nature Physic

Formation and Propagation of Matter Wave Soliton Trains

Attraction between atoms in a Bose-Einstein-Condensate renders the condensate unstable to collapse. Confinement in an atom trap, however, can stabilize the condensate for a limited number of atoms, as was observed with 7Li, but beyond this number, the condensate collapses. Attractive condensates constrained to one-dimensional motion are predicted to form stable solitons for which the attractive interactions exactly compensate for the wave packet dispersion. Here we report the formation or bright solitons of 7Li atoms created in a quasi-1D optical trap. The solitons are created from a stable Bose-Einstein condensate by magnetically tuning the interactions from repulsive to attractive. We observe a soliton train, containing many solitons. The solitons are set in motion by offsetting the optical potential and are observed to propagate in the potential for many oscillatory cycles without spreading. Repulsive interactions between neighboring solitons are inferred from their motion

Constructing Dirac linear fermions in terms of non-linear Heisenberg spinors

We show that the massive (or massless) neutrinos can be described as special states of Heisenberg nonlinear spinors. As a by-product of this decomposition a particularly attractive consequence appears: the possibility of relating the existence of only three species of mass-less neutrinos to such internal non-linear structure. At the same time it allows the possibility that neutrino oscillation can occurs even for massless neutrinos

Dynamic mode II delamination in through thickness reinforced composites

Through thickness reinforcement (TTR) technologies have been shown to provide effective delamination resistance for laminated composite materials. The addition of this reinforcement allows for the design of highly damage tolerant composite structures, specifically when subjected to impact events. The aim of this investigation was to understand the delamination resistance of Z-pinned composites when subjected to increasing strain rates. Z-pinned laminated composites were manufactured and tested using three point end notched flexure (3ENF) specimens subjected to increasing loading rates from quasi-static (~0m/s) to high velocity impact (5m/s), using a range of test equipment including drop weight impact tower and a split Hopkinson bar (SHPB). Using a high speed impact camera and frame by frame pixel tracking of the strain rates, delamination velocities as well as the apparent fracture toughness of the Z-pinned laminates were measured and analysed. Experimental results indicate that there is a transition in the failure morphology of the Z-pinned laminates from quasi-static to high strain rates. The fundamental physical mechanisms that generate this transition are discussed

The development and application of a new tool to assess the adequacy of the content and timing of antenatal care

Abstract Background: Current measures of antenatal care use are limited to initiation of care and number of visits. This study aimed to describe the development and application of a tool to assess the adequacy of the content and timing of antenatal care. Methods: The Content and Timing of care in Pregnancy (CTP) tool was developed based on clinical relevance for ongoing antenatal care and recommendations in national and international guidelines. The tool reflects minimal care recommended in every pregnancy, regardless of parity or risk status. CTP measures timing of initiation of care, content of care (number of blood pressure readings, blood tests and ultrasound scans) and whether the interventions were received at an appropriate time. Antenatal care trajectories for 333 pregnant women were then described using a standard tool (the APNCU index), that measures the quantity of care only, and the new CTP tool. Both tools categorise care into 4 categories, from ‘Inadequate’ (both tools) to ‘Adequate plus’ (APNCU) or ‘Appropriate’ (CTP). Participants recorded the timing and content of their antenatal care prospectively using diaries. Analysis included an examination of similarities and differences in categorisation of care episodes between the tools. Results: According to the CTP tool, the care trajectory of 10,2% of the women was classified as inadequate, 8,4% as intermediate, 36% as sufficient and 45,3% as appropriate. The assessment of quality of care differed significantly between the two tools. Seventeen care trajectories classified as ‘Adequate’ or ‘Adequate plus’ by the APNCU were deemed ‘Inadequate’ by the CTP. This suggests that, despite a high number of visits, these women did not receive the minimal recommended content and timing of care. Conclusions: The CTP tool provides a more detailed assessment of the adequacy of antenatal care than the current standard index. However, guidelines for the content of antenatal care vary, and the tool does not at the moment grade over-use of interventions as ‘Inappropriate’. Further work needs to be done to refine the content items prior to larger scale testing of the impact of the new measure

Prompt letters to reduce non-attendance: applying evidence based practice

<p>Abstract</p> <p>Background</p> <p>Non-attendance rates in psychiatric outpatient clinics have been a topic of considerable interest. It is measured as an indicator of quality of service provision. Failed attendances add to the cost of care as well as having an adverse impact on patients leading to missing medications, delay in identifying relapses and increasing waiting list time. Recent trials have demonstrated that prompting letters sent to patients led to a decrease in non-attendance rates. We applied this evidence based practice in our community mental health setting to evaluate its impact.</p> <p>Methods</p> <p>Using a before and after study design, we sent prompting letters to all patients due to attend outpatient clinic appointments for a period of six months in 2007. Non-attendance rates were compared with the corresponding period in 2006. We also looked at trends of non-attendance prior to this intervention and compared results with other parts of our service where this intervention had not been applied.</p> <p>Results</p> <p>1433 prompting letters were sent out to all out-patient appointments made from June to November 2007. This resulted in an average non-attendance rate of 17% which was significantly less compared to 27% between June and November 2006 (RR 0.65, 95% CI 0.56 to 0.76, NNT 11). No downward trend in non-attendance rate was identified either prior to the intervention or when compared with similar teams across the city.</p> <p>Conclusion</p> <p>Prompt letters have been shown to reduce non-attendance rates in previous RCTs and systematic reviews. Our findings demonstrate a reduction in non-attendance rates with prompting letters even under non-trial conditions. Majority of the patients were constant during the two periods compared although there were some changes in medical personnel. This makes it difficult to attribute all the change, solely to the intervention alone. Perhaps our work shows that the results of pragmatic randomised trials are easily applicable and produce similar results in non-randomised settings. We found that prompting letters are a useful and easy to apply evidence based intervention to reduce non-attendance rates with a potential to achieve significant cost savings.</p

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio