Elucidating the role of DEPTOR in Alzheimer's disease

This article has been made available through the Brunel Open Access Publishing Fund.The mammalian or mechanistic target of rapamycin (mTOR) is a Ser/Thr protein kinase that, in response to nutrient stimulation, regulates cellular growth, proliferation, survival, protein synthesis and gene transcription. It has also been implicated in Alzheimer's disease (AD) with neuronal cells and hippocampal slices of AD transgenic mice experiencing dysregulated mTOR and synaptic plasticity in response to treatment with the toxic amyloid β (Aβ1-42) peptide, which has been implicated in AD. DEP domain-containing mTOR-interacting protein (DEPTOR) is a protein which can bind to mTOR and cause its inhibition, and functions as a regulatory protein of mTOR to control its activity. The inhibition of mTOR has been shown to have a neuroprotective effect; in an animal model, it was shown to protect against Aβ-induced neurotoxicity. In the present study, to investigate to role of DEPTOR in a model of AD, we neuronally differentiated the SH-SY5Y cell line and examined the effects of treatment with an Aβ42 peptide, thus mimicking plaque formation. This resulted in a significant increase in mTOR and a significant decrease in DEPTOR expression compared to the unstimulated controls. Moreover, to the best of our knowledge, we demonstrate for the first time a reduction in the protein level of DEPTOR in the precentral gyrus, postcentral gyrus and occipital lobe of a brain with AD compared to a normal control, as well as a significant reduction in DEPTOR expression in samples from late-onset AD (LOAD) compared to early-onset familial AD (EOFAD). The reduction in DEPTOR expression in cases of AD compared to healthy controls can lead to an augmentation of mTOR signalling, leading to Aβ accumulation, which in turn leads to a further reduction in DEPTOR expression. This results in the accumulation of amyloid plaque, shifting the balance from neuroprotection to neurodegeneration

Novel Chitinolytic Enzymes with Biological Activity Against Herbivorous Insects

The soil bacteria, Streptomyces albidoflavus, secretes endochitinases and chitobiosidases that are active over a broad range of pH (4-10). Ingestion of this mixture of chitinolytic enzymes significantly reduced the growth and development of Trichoplusia ni and significantly reduced survival of Myzus persicae, Bemisia argentifolii, and Hypothenemus hampei. Perfusion chromatography was used to separate endochitinases from chitobiosidases. The endochitinases had significantly greater biological activity against Bemisia argentifolii than the chitobiosidases. The utility of chitinolytic enzymes as regulators of populations of herbivorous insects is discusse

Spatial mapping of band bending in semiconductor devices using in-situ quantum sensors

Band bending is a central concept in solid-state physics that arises from local variations in charge distribution especially near semiconductor interfaces and surfaces. Its precision measurement is vital in a variety of contexts from the optimisation of field effect transistors to the engineering of qubit devices with enhanced stability and coherence. Existing methods are surface sensitive and are unable to probe band bending at depth from surface or bulk charges related to crystal defects. Here we propose an in-situ method for probing band bending in a semiconductor device by imaging an array of atomic-sized quantum sensing defects to report on the local electric field. We implement the concept using the nitrogen-vacancy centre in diamond, and map the electric field at different depths under various surface terminations. We then fabricate a two-terminal device based on the conductive two-dimensional hole gas formed at a hydrogen-terminated diamond surface, and observe an unexpected spatial modulation of the electric field attributed to a complex interplay between charge injection and photo-ionisation effects. Our method opens the way to three-dimensional mapping of band bending in diamond and other semiconductors hosting suitable quantum sensors, combined with simultaneous imaging of charge transport in complex operating devices.Comment: This is a pre-print of an article published in Nature Electronics. The final authenticated version is available online at https://dx.doi.org/10.1038/s41928-018-0130-

Full-Shell X-Ray Optics Development at NASA Marshall Space Flight Center

NASAs Marshall Space Flight Center (MSFC) maintains an active research program toward the development of high-resolution, lightweight, grazing-incidence x-ray optics to serve the needs of future x-ray astronomy missions such as Lynx. MSFC development efforts include both direct fabrication (diamond turning and deterministic computer-controlled polishing) of mirror shells and replication of mirror shells (from figured, polished mandrels). Both techniques produce full-circumference monolithic (primary + secondary) shells that share the advantages of inherent stability, ease of assembly, and low production cost. However, to achieve high-angular resolution, MSFC is exploring significant technology advances needed to control sources of figure error including fabrication- and coating-induced stresses and mounting-induced distortions

Is Enrichment Always Enriching and How Would You Know? Unintended Consequences and the Importance of Formal Assessment of Enrichment Programs in Bottlenose Dolphins (Tursiops truncatus)

Bottlenose dolphins (Tursiops truncatus) are viewed as a highly intelligent species capable of complex behaviors. This requires marine parks to maintain dynamic environmental enrichment programs in order to ensure dolphins’ optimal psychological and physiological well-being while in human care. In this study, two experiments were conducted to determine the effects of different forms of enrichment on the behavior of four bottlenose dolphins. In Experiment 1, multiple forms of novel enrichment resulted in a shift away from individual swim patterns – a change that is associated with increased behavioral diversity and so often considered an improvement in animal welfare – but also resulted in avoidance behavior and initially resulted in a decrease in affiliative behavior. In Experiment 2, introducing choice of enrichments resulted in unintended social consequences, such as agonistic behaviors. These two experiments together demonstrated that interpreting the results of enrichment programs may not be as straightforward as often presumed. The results suggest that unique forms of enrichment and variable schedules might be particularly effective but also that consistent evaluation continues to be necessary to minimize unintended behavioral consequences

Nuclear Cryogenic Propulsion Stage

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced NEP

Technology Developments Toward Sub-arc-second X-ray Optics

No abstract availabl

Bendable X-ray Optics for High Resolution Imaging

Current state-of the-art for x-ray optics fabrication calls for either the polishing of massive substrates into high-angular-resolution mirrors or the replication of thin, lower-resolution, mirrors from perfectly figured mandrels. Future X-ray Missions will require a change in this optics fabrication paradigm in order to achieve sub-arcsecond resolution in light-weight optics. One possible approach to this is to start with perfectly flat, light-weight surface, bend it into a perfect cone, form the desired mirror figure by material deposition, and insert the resulting mirror into a telescope structure. Such an approach is currently being investigated at MSFC, and a status report will be presented detailing the results of finite element analyses, bending tests and differential deposition experiments

Nuclear Cryogenic Propulsion Stage for Mars Exploration

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP)

The Nuclear Cryogenic Propulsion Stage

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progres made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP)