Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and β\u3csub\u3e2\u3c/sub\u3e-agonist use

Background Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this brake on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Methods Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β2-adrenergic receptor haplotype determination. Results Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Conclusion Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to β-agonist. The decreased phosphorylation does not appear to be associated with a particular β2-adrenergic receptor haplotype. The observed decrease in VASP phosphorylation suggests greater inhibition of actin reorganization which is necessary for altering attachment and migration required during epithelial repair

Muscle Fatigue Analysis With Optimized Complementary Ensemble Empirical Mode Decomposition and Multi-Scale Envelope Spectral Entropy

The preprocessing of surface electromyography (sEMG) signals with complementary ensemble empirical mode decomposition (CEEMD) improves frequency identification precision and temporal resolution, and lays a good foundation for feature extraction. However, a mode-mixing problem often occurs when the CEEMD decomposes an sEMG signal that exhibits intermittency and contains components with a near-by spectrum into intrinsic mode functions (IMFs). This paper presents a method called optimized CEEMD (OCEEMD) to solve this problem. The method integrates the least-squares mutual information (LSMI) and the chaotic quantum particle swarm optimization (CQPSO) algorithm in signal decomposition. It uses the LSMI to calculate the correlation between IMFs so as to reduce mode mixing and uses the CQPSO to optimize the standard deviation of Gaussian white noise so as to improve iteration efficiency. Then, useful IMFs are selected and added to reconstruct a de-noised signal. Finally, considering that the IMFs contain abundant frequency and envelope information, this paper extracts the multi-scale envelope spectral entropy (MSESEn) from the reconstructed sEMG signal. Some original sEMG signals, which were collected from experiments, were used to validate the methods. Compared with the CEEMD and complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), the OCEEMD effectively suppresses mode mixing between IMFs with rapid iteration. Compared with approximate entropy (ApEn) and sample entropy (SampEn), the MSESEn clearly shows a declining tendency with time and is sensitive to muscle fatigue. This suggests a potential use of this approach for sEMG signal preprocessing and the analysis of muscle fatigue

Interplay between Structure-Specific Endonucleases for Crossover Control during Caenorhabditis elegans Meiosis

The number and distribution of crossover events are tightly regulated at prophase of meiosis I. The resolution of Holliday junctions by structure-specific endonucleases, including MUS-81, SLX-1, XPF-1 and GEN-1, is one of the main mechanisms proposed for crossover formation. However, how these nucleases coordinately resolve Holliday junctions is still unclear. Here we identify both the functional overlap and differences between these four nucleases regarding their roles in crossover formation and control in the Caenorhabditis elegans germline. We show that MUS-81, XPF-1 and SLX-1, but not GEN-1, can bind to HIM-18/SLX4, a key scaffold for nucleases. Analysis of synthetic mitotic defects revealed that MUS-81 and SLX-1, but not XPF-1 and GEN-1, have overlapping roles with the Bloom syndrome helicase ortholog, HIM-6, supporting their in vivo roles in processing recombination intermediates. Taking advantage of the ease of genetic analysis and high-resolution imaging afforded by C. elegans, we examined crossover designation, frequency, distribution and chromosomal morphology in single, double, triple and quadruple mutants of the structure-specific endonucleases. This revealed that XPF-1 functions redundantly with MUS-81 and SLX-1 in executing crossover formation during meiotic double-strand break repair. Analysis of crossover distribution revealed that SLX-1 is required for crossover suppression at the center region of the autosomes. Finally, analysis of chromosome morphology in oocytes at late meiosis I stages uncovered that SLX-1 and XPF-1 promote meiotic chromosomal stability by preventing formation of chromosomal abnormalities. We propose a model in which coordinate action between structure-specific nucleases at different chromosome domains, namely MUS-81, SLX-1 and XPF-1 at the arms and SLX-1 at the center region, exerts positive and negative regulatory roles, respectively, for crossover control during C. elegans meiosis

Association between baseline abundance of Peptoniphilus, a Gram-positive anaerobic coccus, and wound healing outcomes of DFUs

Diabetic foot ulcers (DFUs) lead to nearly 100,000 lower limb amputations annually in the United States. DFUs are colonized by complex microbial communities, and infection is one of the most common reasons for diabetes-related hospitalizations and amputations. In this study, we examined how DFU microbiomes respond to initial sharp debridement and off- loading and how the initial composition associates with 4 week healing outcomes. We employed 16S rRNA next generation sequencing to perform microbial profiling on 50 sam- ples collected from 10 patients with vascularized neuropathic DFUs. Debrided wound sam- ples were obtained at initial visit and after one week from two DFU locations, wound bed and wound edge. Samples of the foot skin outside of the wounds were also collected for compar- ison. We showed that DFU wound beds are colonized by a greater number of distinct bacte- rial phylotypes compared to the wound edge or skin outside the wound. However, no significant microbiome diversity changes occurred at the wound sites after one week of stan- dard care. Finally, increased initial abundance of Gram-positive anaerobic cocci (GPAC), especially Peptoniphilus (p \u3c 0.05; n = 5 subjects), was associated with impaired healing; thus, GPAC’s abundance could be a predictor of the wound-healing outcome

Effect of the Adapted NASA Mission X International Child Fitness Program on Young Children and their Parents in South Korea

Obesity has become a global epidemic. Childhood obesity is global public health concern including in South Korea where 16.2% of boys and 9.9% of girls are overweight or obese in 2011. Effective and sustainable intervention programs are needed for prevention of childhood obesity. Obesity prevention programs for young children may have a greater intervention effect than in older children. The NASA Mission X: Train Like an Astronaut (MX) program was developed to promote children's exercise and healthy eating by tapping into their excitement for training like an astronaut. This study aimed to examine the feasibility and effectiveness of the adapted NASA MX intervention in promoting PA in young children and in improving parents' related perspectives