Sedentary aging results in structural impairment of the neuromuscular junction and may be attenuated by voluntary endurance exercise

An increasingly prominent change in the aging body is the decrease in muscle mass and strength, a condition known as sarcopenia. This is a major cause for the instability in elderly individuals leading to falls and injuries. One possible cause of sarcopenia is the reduced exercise activity of older individuals. The neuromuscular junction (NMJ) is the connection by which nerves control muscle movement. This study mainly aims to investigates the possibility that alterations in the structures of the neuromuscular junction with ageing might contribute to impaired control and physical maintenance of aging muscle. Changes in the NMJ include the loss of nerve terminal from the postsynaptic membrane leading to denervation and fragmentation of postsynaptic clusters of acetylcholine receptors (AChRs) resulting in tiny islands of receptors. Exercise in ageing animals and humans have shown to have some positive effects on sarcopenic related changes like slowing down the rate of loss in muscle mass and strength. In the neuromuscular junction of old animals and rodents that exercised the age related changes were reported to be less severe and in some cases the NMJ recovered

Lightning Prediction for Space Launch Using Machine Learning Based Off of Electric Field Mills and Lightning Detection and Ranging Data

Kennedy Space Center and Cape Canaveral Air Station, FL, where the Air Force conducts space launches, are in an area of frequent lightning strikes, which is main obstacle in meeting launch goals. The 45th Weather Squadron (45th WS) ensures that any weather safety requirements are met during pre-launch and actual space launch. Using only summer months from three years’ worth of lightning detection and ranging (LDAR) and electric field mill (EFM) data from KSC, several feedforward neural networks are constructed. Separate models are built for each EFM and trained by adjusting parameters to forecast lightning 30 minutes out in the surrounding area of each field mill

Energy Efficiency Improvements in Dry Drilling with Optimised Diamond-Like Carbon Coating

We demonstrate enhancements of performance and energy efficiency of cutting tools by deposition of diamond-like carbon (DLC) coatings on machine parts. DLC was deposited on steel drill bits, using plasma enhanced chemical vapour deposition (PECVD) with the acetylene precursor diluted with argon, to produce a surface with low friction and low wear rate. Drill bit performance in dry drilling of aluminium was quantified by analysis of power consumption and swarf flow. Optimised deposition conditions produced drill bits with greatly enhanced performance over uncoated drill bits, showing a 25% reduction in swarf clogging, a 36% reduction in power consumption and a greater than five-fold increase in lifetime. Surface analysis with scanning electron microscopy shows that DLC coated drills exhibit much lower aluminium build up on the trailing shank of the drill, enhancing the anti-adhering properties of the drill and reducing heat generation during operation, resulting in the observed improvements in efficiency. Variation of drilling efficiency with argon dilution of precursor is related to changes in the microstructure of the DLC coating

The impact of glycaemic variability on wound healing in the diabetic foot – a retrospective study of new ulcers presenting to a specialist multidisciplinary foot clinic

Aims: Glycaemic variability – the visit-to-visit variation in HbA1c – plays a possible role in the development of micro and macrovascular disease in patients with diabetes. Whether HbA1c variability is a factor determining wound healing in diabetic foot ulcers remains unknown. We aimed to determine whether HbA1c variability is associated with foot ulcer healing time. Methods: A retrospective analysis of patients presenting to our specialist multidisciplinary foot clinic between July 2013 and March 2015, with at least three HbA1c measurements within five years of presentation and more than two follow-up reviews. HbA1c variation was measured by magnitude of standard deviation. Results: 629 new referrals were seen between July 2013 and March 2015. Of these, 172 patients had their number of days to healing recorded and sufficient numbers of HbA1c values to determine variability. The overall geometric mean days to heal was 91.1 days (SD 80.8 to 102.7). In the low HbA1c variability group the geometric mean days to heal was 78.0 days (60.2 to 101.2) vs 126.9 days (102.0 to 158.0) in the high Hb1Ac variability group (p=0.032). Those with low HbA1c (< 58 mmol/mol) and low variability healed faster than those with high HbA1c and high variability (73.5 days [59.5 to 90.8] vs 111.0 days [92.0 to 134.0], p=0.007). Additionally, our results show that time to healing is more dependent on the mean HbA1c than the variability in HbA1c (p=0.007). Conclusions/interpretation: Our data suggest that there was a significant association between HbA1c variability and healing time in diabetic foot ulcers

Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition

SummaryNucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs) specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg

Collective Quartics from Simple Groups

This article classifies Little Higgs models that have collective quartic couplings. There are two classes of collective quartics: Special Cosets and Special Quartics. After taking into account dangerous singlets, the smallest Special Coset models are SU(5)/SO(5) and SU(6)/Sp(6). The smallest Special Quartic model is SU(5)/SU(3) x SU(2) x U(1) and has not previously been considered as a candidate Little Higgs model.Comment: 22 pages, 2 figure

Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition

SummaryNucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs) specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg

Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine

Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is similar to 2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future.Peer reviewe

Expression and function of the LIM homeobox containing genes Lhx3 and Lhx4 in the mouse placenta

The LIM homeobox containing genes of the LIM-3 group, Lhx3 and Lhx4 , are critical for normal development. Both genes are involved in the formation of the pituitary and the motoneuron system and loss of either gene causes perinatal lethality. Previous studies had shown that Lhx3 is overexpressed in hyperplastic placentas of mouse interspecies hybrids. To determine the role of LHX3 in the mouse placenta, we performed expression and function analyses. Our results show that Lhx3 exhibits specific spatial and temporal expression in the mouse placenta. However, deletion of Lhx3 does not produce a placental phenotype. To test whether this is due to functional substitution by Lhx4 , we performed a phenotype analysis of Lhx3 −/−; Lhx4 −/− double-mutant placentas. A subset of Lhx3 −/−; Lhx4 −/− placentas exhibited abnormal structure of the labyrinth. However, absence of both LIM-3 genes did not interfere with placental transport nor consistently with expression of target genes such as Gnrhr . Thus, LHX3 and LHX4 appear to be dispensable for placental development and function. Developmental Dynamics 237:1517-1525, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58577/1/21546_ftp.pd

Single Spin Asymmetry ANA_N in Polarized Proton-Proton Elastic Scattering at s=200\sqrt{s}=200 GeV

We report a high precision measurement of the transverse single spin asymmetry $A_N$ at the center of mass energy $\sqrt{s}=200$ GeV in elastic proton-proton scattering by the STAR experiment at RHIC. The $A_N$ was measured in the four-momentum transfer squared $t$ range $0.003 \leqslant |t| \leqslant 0.035$ \GeVcSq, the region of a significant interference between the electromagnetic and hadronic scattering amplitudes. The measured values of $A_N$ and its $t$-dependence are consistent with a vanishing hadronic spin-flip amplitude, thus providing strong constraints on the ratio of the single spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated by the Pomeron amplitude at this $\sqrt{s}$, we conclude that this measurement addresses the question about the presence of a hadronic spin flip due to the Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure