Relationship Between Changes in EMG and Respiratory Sinus Arrhythmia in a Study of Relaxation Therapy for Asthma

This paper reports the relationships among changes in cardiovagal activity, surface EMG, and measures of pulmonary function in a study of relaxation therapy for asthma. Changes in FEV ₁ /FVC were negatively correlated with those in cardiac interbeat interval, consistent with the hypothesis that relaxation-induced changes in airway function are mediated autonomically, with increased vagal tone and/or decreased sympathetic arousal producing bronchoconstriction. Contrary to Kotses's theory of a vagal-trigeminal reflex as mediator for relaxation-induced improvement in asthma, decreases in pulmonary function occurred during relaxation sessions, accompanied by increases in cardiovagal activity, and within-session changes in frontal EMG in the first session of training were positively associated with changes in a measure of pulmonary function (FEV1/FVC). However, consistent with this hypothesis, first-session frontalis EMG changes were positively associated with changes in respiratory sinus arrhythmia, and last-session changes in cardiac interbeat interval were positively associated with changes in FEV1/FVC. The results suggest that the immediate effects of generalized relaxation instruction can be associated with a parasympathetic rebound, which, in turn, may induce countertherapeutic changes in asthma. However, the effects of specific facial muscle relaxation remain uncelar.     

Large scale genotype-phenotype correlation analysis based on phylogenetic trees

We provide two methods for identifying changes in genotype that are correlated with changes in a phenotype implied by phylogenetic trees. The first method, VENN, works when the number of branches over which the change occurred are modest. VENN looks for genetic changes that are completely penetrant with phenotype changes on a tree. The second method, CCTSWEEP, allows for a partial matching between changes in phenotypes and genotypes and provides a score for each change using Maddison's concentrated changes test. The mutations that are highly correlated with phenotypic change can be ranked by score. We use these methods to find SNPs correlated with resistance to Bacillus anthracis in inbred mouse strains. Our findings are consistent with the current biological literature, and also suggest potential novel candidate genes.     

Flowering range changes across an elevation gradient in response to warming summer temperatures

Many studies have demonstrated plant response to warming temperatures, both as advancement in the timing of phenological events and in range shifts. Mountain gradients are ideal laboratories for studying species range changes. In this study of 363 plant species in bloom collected in five segments across a 1200 m (4158 ft) elevation gradient, we look for changes in species flowering ranges over a 20-year period. Ninety-three species (25.6%) exhibited a significant change in the elevation at which they flowered from the first half to the second half of the record, with many of these changes occurring at higher elevations. Most of the species exhibiting the changes were perennial plants. Interestingly, though many changes in flowering range were specific to higher elevations, range changes occurred all across the gradient. The changes reported in this study are concurrent with significant increases in summer temperatures across the region and are consistent with observed changes around the globe.     

Vegetation succession in lakes of West Connemara,Ireland: comparing predicted and actual changes

Abstract. Changes in the vegetation of lakes and wetlands were investigated over a period of 18 years. It was assumed that changes in vegetation were related to changes in agricultural land use resulting in increased phosphate levels in surface waters. Data were collected in 1975, 1988 and 1993. Multivariate techniques were used to relate changes in vegetation to changes in environmental factors. With the use of a Markovian chain model, vegetation development was projected into the future. Projections based on vegetation dynamics between 1975 and 1988 were compared with actual changes in the vegetation. The vegetation dynamics appeared stable on a regional scale but quite dynamic on a local scale. A continuous decline in species diversity was noted as well as an overall increase of phosphate level. However, only minor changes in vegetation could be attributed to this increase of phosphate. Major changes were a result of fluctuations in water level. These changes coincide with periods of drier and wetter climate. Because of the fluctuating nature of these changes, predicted vegetation change did deviate from the observed change.     

Sodium butyrate alters erythropoietin glycosylation via multiple mechanisms

Recombinant human erythropoietin (rHuEPO) produced in a human kidney fibrosarcoma cell line, HT1080, was used as a model to study the effects of sodium butyrate (SB) on protein glycosylation. Treatment with 2 mM SB resulted in complex changes with respect to sugar nucleotide pools including an increase in UDP-Gal and a decrease in UDP-GlcNac. In addition, polylactosamine structures present on rHuEPO increased after SB treatment. To determine if these phenotypic changes correlated with changes in mRNA abundance, we profiled mRNA levels over a 24-h period in the presence or absence of SB using oligonucleotide microarrays. By filtering our data through a functional glycomics gene list associated with the processes of glycan degradation, glycan synthesis, and sugar nucleotide synthesis and transport we identified 26 genes with significantly altered mRNA levels. We were able to correlate the changes in message in six of these genes with measurable phenotypic changes within our system including: neu1, b3gnt6, siat4b, b3gnt1, slc17a5, and galt. Interestingly, for the two genes: cmas and gale, our measurable phenotypic changes did not correlate with changes in mRNA expression. These data demonstrate both the utility and pit falls of coupling biochemical analysis with high throughput oligonucleotide microarrays to predict how changes in cell culture environments will impact glycoprotein oligosaccharide content.     

Genomic changes in resynthesized Brassica napus and their effect on gene expression and phenotype

Many previous studies have provided evidence for genome changes in polyploids, but there are little data on the overall population dynamics of genome change and whether it causes phenotypic variability. We analyzed genetic, epigenetic, gene expression, and phenotypic changes in approximately 50 resynthesized Brassica napus lines independently derived by hybridizing double haploids of Brassica oleracea and Brassica rapa. A previous analysis of the first generation (S0) found that genetic changes were rare, and cytosine methylation changes were frequent. Our analysis of a later generation found that most S0 methylation changes remained fixed in their S5 progeny, although there were some reversions and new methylation changes. Genetic changes were much more frequent in the S5 generation, occurring in every line with lines normally distributed for number of changes. Genetic changes were detected on 36 of the 38 chromosomes of the S5 allopolyploids and were not random across the genome. DNA fragment losses within lines often occurred at linked marker loci, and most fragment losses co-occurred with intensification of signal from homoeologous markers, indicating that the changes were due to homoeologous nonreciprocal transpositions (HNRTs). HNRTs between chromosomes A1 and C1 initiated in early generations, occurred in successive generations, and segregated, consistent with a recombination mechanism. HNRTs and deletions were correlated with qualitative changes in the expression of specific homoeologous genes and anonymous cDNA amplified fragment length polymorphisms and with phenotypic variation among S5 polyploids. Our data indicate that exchanges among homoeologous chromosomes are a major mechanism creating novel allele combinations and phenotypic variation in newly formed B. napus polyploids.     

Quantitative radionuclide assessment of total pulmonary vascular volume changes

Current techniques do not permit continuous and noninvasive assessments of changes in total pulmonary intravascular volume. Hence, the present study was undertaken to determine whether quantitative radionuclide imaging can be used to determine the direction and estimate the magnitude of total pulmonary vascular volume changes. The pulmonary circulation was separately perfused at a constant rate via the pulmonary artery and drained at a constant pressure via the left atrium in nine dogs. Changes in pulmonary intravascular volume were recorded as reciprocal changes in extracorporeal reservoir volume during phenylephrine or isoproterenol administration, a 20% increase in pulmonary artery flow or a 5 mmHg (1 mmHg = 133.32 Pa) decrease in left atrial pressure. Erythrocytes were labeled with technetium-99m and pulmonary volume changes were determined from tissue attenuation, blood radioactivity, and changes in total pulmonary radioactivity obtained with a gamma-camera. During each of the interventions, count changes correlated with volume changes (r greater than or equal to 0.75). The technique reliably detected volume changes as small as 10 mL. For all 531 individual pairs of radionuclide- and reservoir-determined volume changes, the correlation between reservoir-determined and radionuclide-estimated pulmonary intravascular volume changes was 0.87. The standard error of the radionuclide estimate was 21 mL. Hence, the present study demonstrates that quantitative radionuclide imaging can be used to continuously and noninvasively determine total pulmonary vascular volume changes.     

Spin-labeling studies of the conformational changes in the vicinity of D36, D38, T46, and E161 of bacteriorhodopsin during the photocycle.

Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin-labeled bacteriorhodopsin mutants is used to study structural changes during the photocycle. After exchange of the native amino acids D36 and D38 in the A-B loop, E161 in the E-F loop, and T46 in the putative proton channel by cysteines, these positions were modified by a methanethiosulfonate spin label. Time-resolved EPR spectroscopy reveals spectral changes during the photocycle for the mutants with spin labels attached to C36, C161, and C46. A comparison of the transient spectral amplitudes with simulated EPR difference spectra shows that the detected signals are due to changes in the spin label mobility and not to possible polarity changes in the vicinity of the attached spin label. The kinetic analysis of the EPR and the visible data with a global fitting procedure exhibits a structural rearrangement near position 161 in the E-F loop in the M state. The environmental changes at positions 36 and 46, however, occur during the M-to-N transition. All structural changes reverse with the recovery of the BR ground state. No structural changes are detected with a spin label attached to C38.     

Intestinal epithelial cell-derived interleukin-7: A mechanism for the alteration of intraepithelial lymphocytes in a mouse model of total parenteral nutrition

Total parenteral nutrition (TPN), with the absence of enteral nutrition, results in profound changes to both intestinal epithelial cells (EC) as well as the adjacent intraepithelial lymphocyte (IEL) population. Intestinal EC are a rich source of IL-7, a critical factor to support the maintenance of several lymphoid tissues, and TPN results in marked EC changes. On this basis, we hypothesized that TPN would diminish EC-derived IL-7 expression and that this would contribute to the observed changes in the IEL population. Mice received enteral food and intravenous crystalloid solution (control group) or TPN. TPN administration significantly decreased EC-derived IL-7 expression, along with significant changes in IEL phenotype; decreased IEL proliferation; and resulted in a marked decrease in IEL numbers. To better determine the relevance of TPN-related changes in IL-7, TPN mice supplemented with exogenous IL-7 or mice allowed ad libitum feeding and treated with exogenous administration of anti-IL-7 receptor (IL-7R) antibody were also studied. Exogenous IL-7 administration in TPN mice significantly attenuated TPN-associated IEL changes, whereas blocking IL-7R in normal mice resulted in several similar changes in IEL to those observed with TPN. These findings suggest that a decrease in EC-derived IL-7 expression may be a contributing mechanism to account for the observed TPN-associated IEL changes.     

Whole-genome methylation analysis of aging human tissues identifies age-related changes in developmental and neurological pathways

Age-associated changes in the DNA methylation state can be used to assess the pace of aging. However, it is not understood what mechanisms drive these changes and whether these changes affect the development of aging phenotypes and the aging process in general. This study was aimed at gaining a more comprehensive understanding of aging-related methylation changes across the whole genome, and relating these changes to biological functions. It has been shown that skeletal muscle and blood monocytes undergo typical changes with aging. Using whole-genome bisulfite sequencing, we sought to characterize the genome-wide changes in methylation of DNA derived from both skeletal muscle and blood monocytes, and link these changes to specific genes and pathways through enrichment analysis. We found that methylation changes occur with aging at the locations enriched for developmental and neuronal pathways regulated in these two peripheral tissues. These results contribute to our understanding of changes in epigenome in human aging.     

Amino acid sequence coevolution in the insect bursicon ligand-receptor system

The pattern of amino acid residue replacement in the components of the bursicon signaling system (involving the BURSα/BURSβ heterodimer and its receptor BURSrec) was reconstructed across a phylogeny of 17 insect species, in order to test for the co-occurrence of replacements at sets of individual sites. Sets of three or more branches with perfectly concordant changes occurred to a greater extent than expected by chance, given the observed level of amino acid change. The latter sites (SPC sites) were found to have distinctive characteristics: (1) the mean number of changes was significantly lower at SPC sites than that at other sites with multiple changes; (2) SPC sites had a significantly greater tendency toward parallel amino acid changes than other sites with multiple changes, but no greater tendency toward convergent changes; and (3) parallel changes tended to involve relatively similar amino acids, as indicated by relatively low mean chemical distances. The results implicated functional constraint, permitting only a limited subset of amino acids in a given site, as a major factor in causing both parallel amino acid replacement and coordinated amino acid changes in different sites of the same protein and of interacting proteins in this system.     

Age-related histochemical and histological changes in the knee-joint cartilage of C57B1 mice and their significance for the pathogenesis of osteoarthrosis. I. Oxidative enzymes

For a better understanding of the part played by the aging of cartilage in the pathogenesis ofosteoarthrosis, we attempted to detect functional age-related changes in the knee-joint cartilage of C57B1 mice using histochemical methods and to correlate these changes with the concomitant histological changes. A comparison of 57- and 97-week-old mice revealed a statistically significant age-related focal loss of activity for a number of oxidative enzymes of the chondrocytes. There was an associated significant increase in regressive changes of the chondrocytes. A relation probably exists between these two changes, inasmuch as the focal loss of enzyme activity precedes and possibly gives rise to the regressive changes. A comparison with the changes described in the articular cartilage of other species including man suggests that the phenomena observed are inherent age-related changes. The loss of activity of all the enzymes investigated indicates a far-reaching derangement of cellular metabolism, leading to impaired synthesis of proteoglycans. Since these compounds are major determinants of the physical properties of articular cartilage, the changes described might render the cartilage more vulnerable and might thus play a major part in the pathogenesis of osteoarthrosis.     

How a small change in retinal leads to G-protein activation: initial events suggested by molecular dynamics calculations

Rhodopsin is the prototypical G-protein coupled receptor, coupling light activation with high efficiency to signaling molecules. The dark-state X-ray structures of the protein provide a starting point for consideration of the relaxation from initial light activation to conformational changes that may lead to signaling. In this study we create an energetically unstable retinal in the light activated state and then use molecular dynamics simulations to examine the types of compensation, relaxation, and conformational changes that occur following the cis-trans light activation. The results suggest that changes occur throughout the protein, with changes in the orientation of Helices 5 and 6, a closer interaction between Ala 169 on Helix 4 and retinal, and a shift in the Schiff base counterion that also reflects changes in sidechain interactions with the retinal. Taken together, the simulation is suggestive of the types of changes that lead from local conformational change to light-activated signaling in this prototypical system.     

Measurement of mucosal blood flow in the canine intestine with laser doppler velocimetry

Laser Doppler velocimetry is a technique for continuous estimation of changing blood flow in the surface of a tissue and does not require invasion of the circulation. This technique is based upon the Doppler principle that a shift in the frequency of an electromagnetic wave emitted or reflected from a moving object is proportional to the velocity of the object. The capacity of Laser Doppler velocimetry to estimate changes in intestinal mucosal blood flow was tested in a canine free flow preparation. In anesthetized dogs in which a segment of ileum was isolated, simultaneous measurements of instantaneous changes in total blood flow (measured with the electromagnetic blood flow meter) and instantaneous changes in presumed mucosal blood flow (using laser Doppler velocimetry) were obtained. Determinations were made during conditions of rest, prostacyclin induced vasodilation and norepinephrine induced vasoconstriction. Changes in laser Doppler velocimeter readings were qualitatively similar to and temporally related to changes in total blood flow to the gut segment during administration of the vasoactive drugs. The magnitude and direction of changes with the two measurements were significantly correlated. Stabilizing the laser probe on the mucosal surface to ensure reproducible readings proved technically difficult. Pharmacologically induced changes in laser Doppler velocimeter estimated changes in flow were more readily correlated with changes in electromagnetic flow meter readings than were control values obtained with the two methods.     

Plasma Membrane Lipids Associated with Genetic Variability in Freezing Tolerance and Cold Acclimation of Solanum Species

Simultaneous comparisons were made between a freezing-tolerant, cold-acclimating (CA) wild potato species (Solanum commersonii) and a freezing-sensitive, nonacclimating (NA) cultivated species (Solanum tuberosum). Comparative studies allowed differentiation of plasma membrane lipid changes associated with increased freezing tolerance following CA from lipid changes that can result from metabolic adjustment to reduced temperature during CA. Following CA treatment lipid changes found in both the NA and CA species included a decrease in palmitic acid, an increase in unsaturated to saturated fatty acid ratio, an increase in free sterols, an increase in sitosterol, and a slight decrease in cerebrosides. Lipid changes detected only in the acclimating species included an increase in phosphatidylethanolamine, a decrease in sterol to phospholipid ratio, an increase in linoleic acid, a decrease in linolenic acid, and an increase in acylated steryl glycoside to steryl glycoside ratio. These changes were either absent or opposite in the NA species, suggesting an association of these lipid changes with CA. Furthermore, the lipid changes associated with increased freezing tolerance during CA were distinct from lipid differences between the two species in the NA state.     

Hydroelectricity and fish: a synopsis of comprehensive studies of upstream and downstream passage of anadromous wild Atlantic salmon, <Emphasis Type="Italic">Salmo salar</Emphasis>, on the Exploits River,Canada

Microalgal biofilms are associated with considerable variability in the properties of natural sediments, yet little effort has been made to isolate micro-scale spatial and temporal changes in sediment properties caused by the growth of a biofilm. Understanding the changes associated with biofilm growth and quantifying the time scales over which these changes occur is important for developing suitable experimental designs and for understanding how biofilms mediate sediment properties and processes. The development of a microphytobenthic biofilm and associated changes in the sediment was investigated over 45 days in the laboratory. The biogeochemical properties of the sediment: bulk density, water content, chlorophyll a concentration and colloidal carbohydrate concentration were measured on a sub-millimetre scale in the top 2 mm. The erosion threshold was measured with a Cohesive Strength Meter (CSM). Biofilm development was rapid, with changes in the properties occurring after 1 day and a visible film forming after just 3 days. The largest changes in sediment properties tended to occur in the surface 200 μm through time, with some variables also showing a differing response with depth. There were significant changes in water content, chlorophyll a concentration, colloidal carbohydrate concentration and erosion threshold in the surface 2 mm, with a general trend to increase with time. Bulk density was highly variable and did not show a consistent pattern of change with time. Erosion threshold was positively correlated with water content, chlorophyll a and colloidal carbohydrate in the surface 200 μm and these were also positively correlated with each other. Low Temperature Scanning Electron Microscopy (LTSEM) images revealed changes in the surface sediment structure and the formation of a thick multi-layer biofilm. The rapidity of biofilm growth and development and the associated changes to the sediment should be considered when designing experiments that investigate biofilms and properties of sediments and/or that involve biocide treatments or disturbance to the sediment.     

PROTONATION AND CHLOROPLAST MEMBRANE STRUCTURE

Light changes the structure of chloroplasts. This effect was investigated by high resolution electron microscopy, photometric methods, and chemical modification. (a) A reversible contraction of chloroplast membrane occurs upon illumination, dark titration with H⁺, or increasing osmolarity. These gross structural changes arise from a flattening of the thylakoids, with a corresponding decrease in the spacing between membranes. Microdensitometry showed that illumination or dark addition of H⁺ resulted in a 13–23% decrease in membrane thickness. Osmotically contracted chloroplasts do not show this effect. (b) Rapid glutaraldehyde fixation during actual experiments revealed that transmission changes are closely correlated with the spacing changes and therefore reflect an osmotic mechanism, whereas the light scattering changes have kinetics most similar to changes in membrane thickness or conformation. (c) Kinetic analysis of light scattering and transmission changes with the changes in fluorescence of anilinonaphthalene sulfonic acid bound to membranes revealed that fluorescence preceded light scattering or transmission changes. (d) It is concluded that the temporal sequence of events following illumination probably are protonation, changes in the environment within the membrane, change in membrane thickness, change in internal osmolarity accompanying ion movements with consequent collapse and flattening of thylakoid, change in the gross morphology of the inner chloroplast membrane system, and change in the gross morphology of whole chloroplasts.     

Heritable Epigenetic Changes Alter Transgenerational Waveforms Maintained by Cycling Stores of Information

Our view of heredity can potentially be distorted by the ease of introducing heritable changes in the replicating gene sequences but not in the cycling assembly of regulators around gene sequences. Here, key experiments that have informed the understanding of heredity are reinterpreted to highlight this distortion and the possible variety of heritable changes are considered. Unlike heritable genetic changes, which are always associated with mutations in gene sequence, heritable epigenetic changes can be associated with physical or chemical changes in molecules or only changes in the system. The transmission of cycling stores along the continuous lineage of cells that connects successive generations creates waves of activity and localization of the molecules that together form the cell code for development in each generation. As a result, heritable epigenetic changes can include any that can alter a wave such as changes in form, midline, frequency, amplitude, or phase. Testing this integrated view of all heritable information will require the concerted application of multiple experimental approaches across generations.     

Comparison of methods to assess water column primary production in wetlands

We compared a number of techniques to measure water column autotroph production in a shallow, hypereutrophic wetland: diurnal oxygen changes; light and dark bottle incubations; chlorophyll a concentrations; daily changes in pH; and algal volume. Productivity from diurnal oxygen changes calculated at 0.25, 0.5, 1, 2, 3, and 4 h intervals give similar estimates, but not 12 h intervals (dawn-dusk-dawn). Net productivity in bottles was slightly lower than that indicated by diurnal oxygen changes, and gross productivity in bottles was much lower than diurnal changes. Changes in pH correlated well with gross and net productivity measurements, as well as algal volume. Chlorophyll a is correlated with diurnal and bottle net productivity measurements and pH changes, but not algal volume. Since daily pH flux and oxygen changes provide a better overall assessment of ecosystem processes than standing crop or bottle incubations, they could be useful measurements for ecological engineers interested in assessing the ecosystem function.     

Regional left ventricular performance during normal and obstructed spontaneous respiration

To clarify the effects of respiration on left ventricular (LV) dimensions and shortening, we studied chronically instrumented dogs with endocardial sonomicrometer crystals in the anterior-posterior (AP), septal to lateral (SL), and long axes (LA) following pericardiectomy. Ten anesthetized dogs were examined during spontaneous unobstructed respiration, partial inspiratory obstruction (PIO), and Mueller maneuvers (MM). During unobstructed inspiration, end-diastolic dimensions (EDD) demonstrated a significant increase in the AP and a similar decrease in the SL axis (i.e., noncongruent shape changes). During PIO only the SL EDD diminished significantly, while no significant changes occurred in any EDD during MM. Individual dogs also demonstrated noncongruent shape changes at end systole during inspiration. However, the end-systolic dimensions for the entire group demonstrated a significant increase in one dimension during each inspiratory mode with no significant changes in the other two axes suggesting an increased ventricular volume. Regional shortening declined only in the SL axis during both unobstructed respiration and PIO. Spontaneous sighs with large tidal volumes, yet smaller changes in pleural pressure than during the MM, were associated with marked noncongruent shape changes in both diastole and systole. We conclude that 1) estimates of LV volumes during respiration based on only one or two axes and assuming regional congruent shape changes may be misleading; and 2) lung volume changes can affect LV geometry independently of changes in pleural pressure.