tRNA Dysregulation in Neurodevelopmental and Neurodegenerative Diseases.

Transfer RNAs (tRNAs) decode messenger RNA codons to peptides at the ribosome. The nuclear genome contains many tRNA genes for each amino acid and even each anticodon. Recent evidence indicates that expression of these tRNAs in neurons is regulated, and they are not functionally redundant. When specific tRNA genes are nonfunctional, this results in an imbalance between codon demand and tRNA availability. Furthermore, tRNAs are spliced, processed, and posttranscriptionally modified. Defects in these processes lead to neurological disorders. Finally, mutations in the aminoacyl tRNA synthetases (aaRSs) also lead to disease. Recessive mutations in several aaRSs cause syndromic disorders, while dominant mutations in a subset of aaRSs lead to peripheral neuropathy, again due to an imbalance between tRNA supply and codon demand. While it is clear that disrupting tRNA biology often leads to neurological disease, additional research is needed to understand the sensitivity of neurons to these changes

Application of Halon 1301 to the Prevention of or Extinguishment of Aerozine -50 Fires

An investigation was conducted into the possibility of using Halon 1301 (bromotrifluoromethane) to inert enclosed, personnel-occupied spaces where spills of Aerozine-50 might occur. The effectiveness of this agent in extinguishing Aerozine-50 fires was also investigated. The concentrations of Halon 1301 required to inert Aerozine-50 vapor-air mixtures depended upon the fuel vapor concentration; except at very high fuel concentration, the amount required was always less than that for nitrogen. High concentrations of Halon 1301 are required to extinguish Aerozine-50 fires, and extinguishment appears possible only during the early stages of burning, before the propellant becomes too concentrated in the high-boiling hydrazine component. There is no advantage in the simultaneous application of C02 and Halon 1301, but the concurrent application of H2O and Halon 1301 provides relatively easy extinguishment

Cell adhesion to agrin presented as a nanopatterned substrate is consistent with an interaction with the extracellular matrix and not transmembrane adhesion molecules

Molecular spacing is important for cell adhesion in a number of ways, ranging from the ordered arrangement of matrix polymers extracellularly, to steric hindrance of adhesion/signaling complexes intracellularly. This has been demonstrated using nanopatterned RGD peptides, a canonical extracellular matrix ligand for integrin interactions. Cell adhesion was greatly reduced when the RGD-coated nanoparticles were separated by more than 60 nm, indicating a sharp spacing-dependent threshold for this form of cell adhesion. RESULTS: Here we show a similar dependence of cell adhesion on the spacing of agrin, a protein that exists as both a secreted, matrix-bound form and a type-2 transmembrane form in vivo. Agrin was presented as a substrate for cell adhesion assays by anchoring recombinant protein to gold nanoparticles that were arrayed at tunable distances onto glass coverslips. Cells adhered well to nanopatterned agrin, and when presented as uniformly coated substrates, adhesion to agrin was comparable to other well-studied adhesion molecules, including N-Cadherin. Adhesion of both mouse primary cortical neurons and rat B35 neuroblastoma cells showed a spacing-dependent threshold, with a sharp drop in adhesion when the space between agrin-coated nanoparticles increased from 60 to 90 nm. In contrast, adhesion to N-Cadherin decreased gradually over the entire range of distances tested (uniform, 30, 60, 90, and 160 nm). The spacing of the agrin nanopattern also influenced cell motility, and peptide competition suggested adhesion was partially integrin dependent. Finally, differences in cell adhesion to C-terminal agrin fragments of different lengths were detected using nanopatterned substrates, and these differences were not evident using uniformly coated substrates. CONCLUSION: These results suggest nanopatterned substrates may provide a physiological presentation of adhesive substrates, and are consistent with cells adhering to agrin through a mechanism that more closely resembles an interaction with the extracellular matrix than a transmembrane adhesion molecule

On Embedding Rings in Clean Rings

A clean ring is one in which every element is a sum of an idempotent and a unit. It is shown that every ring can be embedded in a clean ring as an essential ring extension. It is seen that the centre of a clean ring need not be a clean ring. There is no “clean hull” of a ring. A family of examples is given where there is a ring R, not a clean ring, embedded in a commutative clean ring S so that there is no clean ring T, R T S, minimal with that property. It is also shown that a commutative pm ring (each prime ideal is contained in a unique maximal ideal) cannot be extended to a clean ring by the adjunction of finitely many central idempotents

A cycling and education intervention for the treatment of hip osteoarthritis: A quality improvement replication programme.

Objectives: The Cycling against Hip Pain programme is a 6-week exercise and education treatment pathway for people with hip osteoarthritis. Preliminary results of the Cycling against Hip Pain programme found significant improvements in clinical and patient reported outcome measures for patients referred from primary care. This article evaluates the effectiveness of the changes made to the pathway in a quality improvement replication programme. Methods: The replicated Cycling against Hip Pain programme was delivered between February 2018 and September 2019 in a region of England with a high percentage of adults aged over 65 years. All participants were referred from the orthopaedic outpatient department of the funding hospital (secondary care). The programme was delivered at a local leisure centre and combined 30 min of education on osteoarthritis with 30 min of progressive static cycling, once a week for 6 weeks. Results: The participants on the replicated Cycling against Hip Pain programme did not differ from the original cohort in terms of age or pre-programme weight, however, presented with worse hip symptoms at baseline. Consistent with the findings from the original cohort, participants demonstrated significant improvements to their Oxford Hip Score, 30-s chair stand performance, Timed Up and Go score, Hip Osteoarthritis Outcome Score function and pain, EQ5D health rating, EQ5D-5L score and pain at rest and on weight bearing. In addition, participants reported an increase in knowledge, confidence and motivation to exercise. Conclusion: A 6-week cycling and education intervention for the treatment of hip osteoarthritis provided benefits to function, pain and quality of life for patients referred from secondary care. These results are consistent with findings from patients who were referred from primary care and further support the potential of the pathway in the conservative management of hip osteoarthritis

An Integrated Approach to Studying Rare Neuromuscular Diseases Using Animal and Human Cell-Based Models.

As sequencing technology improves, the identification of new disease-associated genes and new alleles of known genes is rapidly increasing our understanding of the genetic underpinnings of rare diseases, including neuromuscular diseases. However, precisely because these disorders are rare and often heterogeneous, they are difficult to study in patient populations. In parallel, our ability to engineer the genomes of model organisms, such as mice or rats, has gotten increasingly efficient through techniques such as CRISPR/Cas9 genome editing, allowing the creation of precision human disease models. Suc

Reconstruction of contaminant trends in a salt wedge estuary with sediment cores dated using a multiple proxy approach

The Taunton River is a partially mixed tidal estuary in southeastern Massachusetts (USA) which has received significant contaminant inputs, yet little information exists on the history of discharge and the subsequent fate of these contaminants. Three sediment cores taken along a transect were analyzed, reconstructing the spatial and temporal trends of pollution in the estuary. A combination of radiometric dating, contaminant markers, and storm layers from major hurricanes were used to establish age models and sedimentation rates. Age estimates obtained from the different dating methods compared well, establishing an accurate history of contaminant release to the estuary. Polycyclic aromatic hydrocarbons (PAHs) were present in one core at depths corresponding to the early 1860s, earlier than previously established dates of introduction. Temporal and spatial trends of Cr, Cu, Hg and Pb indicated multiple sources of varying input to the river. Polychlorinated biphenyls (PCBs) were present in each of the cores from the 1930s onward, with elevated levels still present in surficial sediments at several sites. A unique organic compound, Topanol, which was produced locally was used as a tracer to track contaminant transport in the river. Tracer data indicates that contaminants are still being transported and deposited to surficial sediments at high concentrations well after their discharge. This reconstruction demonstrates the utility of using multiple dating proxies where often the sole use of radiometric dating techniques is not an option and provides insights into the fate of contaminants discharged decades ago but continue to represent environmental risks

Brane gas-driven bulk expansion as a precursor stage to brane inflation

We propose a new way of obtaining slow-roll inflation in the context of higher dimensional models motivated by string and M theory. In our model, all extra spatial dimensions are orbifolded. The initial conditions are taken to be a hot dense bulk brane gas which drives an initial phase of isotropic bulk expansion. This phase ends when a weak potential between the orbifold fixed planes begins to dominate. For a wide class of potentials, a period during which the bulk dimensions decrease sufficiently slowly to lead to slow-roll inflation of the three dimensions parallel to the orbifold fixed planes will result. Once the separation between the orbifold fixed planes becomes of the string scale, a repulsive potential due to string effects takes over and leads to a stabilization of the radion modes. The conversion of bulk branes into radiation during the phase of bulk contraction leads to reheating.Comment: 5 pages, no figures, same as published on