The effects of pre-habilitative conditioning on unloading-induced adaptations in young and aged neuromuscular systems

The capacity of pre-habilitative conditioning - exercise performed a priori - to mitigate neuromuscular maladaptations to disuse is unclear. This study evaluated pre-habilitation by examining neuromuscular junctions (NMJs) and the myofibers they innervate in young adult and aged muscles. Within each age category, 40 rats were divided into four treatment groups: 1) control, 2) hindlimb suspended (unloaded), 3) prehabilitative conditioning preceding hindlimb suspension, and 4) pre-habilitative conditioning alone. Cytofluorescent staining was used to visualize NMJs, and histochemical staining to assess myofiber profiles (size and type). Statistical analysis featured 2-way ANOVA with main effects for age and treatment, along with interaction. NMJs consistently revealed significant (P \u3c = 0.05) main effects for age, but not treatment, or interaction. Typically, aged NMJs showed elongated nerve terminal branching, and more dispersed post-synaptic clusters of ACh receptors, resulting in reduced post-synaptic area per given length of pre-synaptic branching. Analysis of myofiber profiles showed significant main effects for age, treatment, and their interaction. Aged myofibers were smaller than the young ones and a higher percentage of them were Type I. Aged fibers experienced significantly greater unloading-induced atrophy than the young ones. Pre-habilitative conditioning significantly attenuated unloading-induced atrophy among aged, but not young myofibers. It was also observed that pre-habilitative conditioning alone increased myofiber size among aged, but not young adult muscles. In summary, myofibers were more sensitive than NMJs to the treatment interventions implemented. Although more sensitive to the negative effects of muscle unloading, aged myofibers were also more responsive to the hypertrophic effects of pre-habilitative conditioning. (C) 2012 Elsevier Inc. All rights reserved

The effects of pre-habilitative conditioning on unloading-induced adaptations in young and aged neuromuscular systems

The capacity of pre-habilitative conditioning - exercise performed a priori - to mitigate neuromuscular maladaptations to disuse is unclear. This study evaluated pre-habilitation by examining neuromuscular junctions (NMJs) and the myofibers they innervate in young adult and aged muscles. Within each age category, 40 rats were divided into four treatment groups: 1) control, 2) hindlimb suspended (unloaded), 3) prehabilitative conditioning preceding hindlimb suspension, and 4) pre-habilitative conditioning alone. Cytofluorescent staining was used to visualize NMJs, and histochemical staining to assess myofiber profiles (size and type). Statistical analysis featured 2-way ANOVA with main effects for age and treatment, along with interaction. NMJs consistently revealed significant (P \u3c = 0.05) main effects for age, but not treatment, or interaction. Typically, aged NMJs showed elongated nerve terminal branching, and more dispersed post-synaptic clusters of ACh receptors, resulting in reduced post-synaptic area per given length of pre-synaptic branching. Analysis of myofiber profiles showed significant main effects for age, treatment, and their interaction. Aged myofibers were smaller than the young ones and a higher percentage of them were Type I. Aged fibers experienced significantly greater unloading-induced atrophy than the young ones. Pre-habilitative conditioning significantly attenuated unloading-induced atrophy among aged, but not young myofibers. It was also observed that pre-habilitative conditioning alone increased myofiber size among aged, but not young adult muscles. In summary, myofibers were more sensitive than NMJs to the treatment interventions implemented. Although more sensitive to the negative effects of muscle unloading, aged myofibers were also more responsive to the hypertrophic effects of pre-habilitative conditioning. (C) 2012 Elsevier Inc. All rights reserved

Oxidative Stress Responses and Nutrient Starvation in MCHM Treated Saccharomyces cerevisiae

In 2014, the coal cleaning chemical 4-methylcyclohexane methanol (MCHM) spilled into the water supply for 300,000 West Virginians. Initial toxicology tests showed relatively mild results, but the underlying effects on cellular biology were underexplored. Treated wildtype yeast cells grew poorly, but there was only a small decrease in cell viability. Cell cycle analysis revealed an absence of cells in S phase within thirty minutes of treatment. Cells accumulated in G1 over a six-hour time course, indicating arrest instead of death. A genetic screen of the haploid knockout collection revealed 329 high confidence genes required for optimal growth in MCHM. These genes encode three major cell processes: mitochondrial gene expression/translation, the vacuolar ATPase, and aromatic amino acid biosynthesis. The transcriptome showed an upregulation of pleiotropic drug response genes and amino acid biosynthetic genes and downregulation in ribosome biosynthesis. Analysis of these datasets pointed to environmental stress response activation upon treatment. Overlap in datasets included the aromatic amino acid genes ARO1, ARO3, and four of the five TRP genes. This implicated nutrient deprivation as the signal for stress response. Excess supplementation of nutrients and amino acids did not improve growth on MCHM, so the source of nutrient deprivation signal is still unclear. Reactive oxygen species and DNA damage were directly detected with MCHM treatment, but timepoints showed these accumulated slower than cells arrested. We propose that wildtype cells arrest from nutrient deprivation and survive, accumulating oxidative damage through the implementation of robust environmental stress responses

Hearing the patient voice: Using video intervention/prevention assessment to understand teens with cystic fibrosis

This qualitative study asked two questions: 1) How do teens with cystic fibrosis (CF) feel about their treatments; and 2) What factors lead teens to adhere, or not adhere, to treatments. To answer these questions we used an innovative approach (Video Intervention/Prevention Assessment or VIA), to learn about the experiences of teens with CF. We loaned video camcorders to teens with CF and asked them to create visual narratives of their lives. Researchers logged and coded videotapes, identifying themes that arose from the material. A primary theme was “Doctors don’t understand.” Participants also highlighted the value of routines and parental support in consistently doing treatments. We identify and discuss themes that emerged and discuss how findings can be used to help providers improve care, develop partnerships with patients and increase adherence

Genome-Wide Occupancy of SREBP1 and Its Partners NFY and SP1 Reveals Novel Functional Roles and Combinatorial Regulation of Distinct Classes of Genes

The sterol regulatory element-binding protein (SREBP) family member SREBP1 is a critical transcriptional regulator of cholesterol and fatty acid metabolism and has been implicated in insulin resistance, diabetes, and other diet-related diseases. We globally identified the promoters occupied by SREBP1 and its binding partners NFY and SP1 in a human hepatocyte cell line using chromatin immunoprecipitation combined with genome tiling arrays (ChIP-chip). We find that SREBP1 occupies the promoters of 1,141 target genes involved in diverse biological pathways, including novel targets with roles in lipid metabolism and insulin signaling. We also identify a conserved SREBP1 DNA-binding motif in SREBP1 target promoters, and we demonstrate that many SREBP1 target genes are transcriptionally activated by treatment with insulin and glucose using gene expression microarrays. Finally, we show that SREBP1 cooperates extensively with NFY and SP1 throughout the genome and that unique combinations of these factors target distinct functional pathways. Our results provide insight into the regulatory circuitry in which SREBP1 and its network partners coordinate a complex transcriptional response in the liver with cues from the diet

Engineering Hybrid Epitaxial InAsSb/Al Nanowire Materials for Stronger Topological Protection

The combination of strong spin-orbit coupling, large $g$-factors, and the coupling to a superconductor can be used to create a topologically protected state in a semiconductor nanowire. Here we report on growth and characterization of hybrid epitaxial InAsSb/Al nanowires, with varying composition and crystal structure. We find the strongest spin-orbit interaction at intermediate compositions in zincblende InAs$_{1-x}$Sb$_{x}$ nanowires, exceeding that of both InAs and InSb materials, confirming recent theoretical studies \cite{winkler2016topological}. We show that the epitaxial InAsSb/Al interfaces allows for a hard induced superconducting gap and 2$e$ transport in Coulomb charging experiments, similar to experiments on InAs/Al and InSb/Al materials, and find measurements consistent with topological phase transitions at low magnetic fields due to large effective $g$-factors. Finally we present a method to grow pure wurtzite InAsSb nanowires which are predicted to exhibit even stronger spin-orbit coupling than the zincblende structure.Comment: 10 pages and 5 figure

Pulmonary Function Decline in Amyotrophic Lateral Sclerosis

Background: There has been no comprehensive longitudinal study of pulmonary functions (PFTS) in ALS determining which measure is most sensitive to declines in respiratory muscle strength. Objective: To determine the longitudinal decline of PFTS in ALS and which measure supports Medicare criteria for NIV initiation first. Methods: Serial PFTs (maximum voluntary ventilation (MVV), maximum inspiratory pressure measured by mouth (MIP) or nasal sniff pressure (SNIP), maximum expiratory pressure (MEP), and Forced Vital Capacity (FVC)) were performed over 12 months on 73 ALS subjects to determine which measure showed the sentinel decline in pulmonary function. The rate of decline for each measure was determined as the median slope of the decrease over time. Medicare-based NIV initiation criteria were met if %FVC was ≤ 50% predicted or MIP was ≤ 60 cMH2O. Results: 65 subjects with at least 3 visits were included for analyses. All median slopes were significantly different than zero. MEP and sitting FVC demonstrated the largest rate of decline. Seventy subjects were analyzed for NIV initiation criteria, 69 met MIP criteria first; 11 FVC and MIP criteria simultaneously and none FVC criteria first. Conclusions: MEP demonstrated a steeper decline compared to other measures suggesting expiratory muscle strength declines earliest and faster and the use of airway clearance interventions should be initiated early. When Medicare criteria for NIV initiation are considered, MIP criteria are met earliest. These results suggest that pressure-based measurements are important in assessing the timing of NIV and the use of pulmonary clearance interventions

Fluctuating charge density waves in the Hubbard model

The charge susceptibility of the two-dimensional repulsive Hubbard model is investigated using the diagram technique developed for the case of strong correlations. In this technique, a power series in the hopping constant is used. It is shown that once the Fermi level crosses one of the Hubbard subbands a sharp peak appears in the momentum dependence of the static susceptibility. With further departure from half-filling the peak transforms to a ridge around the $\Gamma$ point. In the considered range 0\leq|1-\bar{n}|\alt 0.2 of the electron filling $\bar{n}$ the static susceptibility is finite which points to the absence of the long-range charge ordering. However, for $|1-\bar{n}|\approx 0.12$ the susceptibility maxima are located halfway between the center and the boundaries of the Brillouin zone. In this case an interaction of carriers with tetragonal distortions can stabilize the charge density wave with the wavelength of four lattice spacings, as observed experimentally in the low-temperature tetragonal phase of lanthanum cuprates. In the range of parameters inherent in cuprate perovskites the character of the susceptibility evolution with $\bar{n}$ depends only weakly on the ratio of the nearest-neighbor hopping constant to the Hubbard repulsion and on details of the initial band structure. The location of the susceptibility maxima in the Brillouin zone is mainly determined by the value of $\bar{n}$.Comment: 8 pages, 4 figure