Multiscale bio-chemo-mechanical model of intimal hyperplasia

We consider a computational multiscale framework of a bio-chemo-mechanical model for intimal hyperplasia. With respect to existing models, we investigate the interactions between hemodynamics, cellular dynamics and biochemistry on the development of the pathology. Within the arterial wall, we propose a mathematical model consisting of kinetic differential equations for key vascular cell types, collagen and growth factors. The luminal hemodynamics is modeled with the Navier–Stokes equations. Coupling hypothesis among time and space scales are proposed to build a tractable modeling of such a complex multifactorial and multiscale pathology. A one-dimensional numerical test-case is presented for validation by comparing the results of the framework with experiments at short and long timescales. Our model permits to capture many cellular phenomena which have a central role in the physiopathology of intimal hyperplasia. Results are quantitatively and qualitatively consistent with experimental findings at both short and long timescales.

     

Timescale analyses of fluctuations in coexisting populations of a native and invasive tree squirrel

1. Competition from invasive species is an increasing threat to biodiversity. In Southern California, the western gray squirrel (Sciurus griseus, WGS) is facing competition from the fox squirrel (Sciurus niger, FS), an invasive congener.
2. We used spectral methods to analyze 140 consecutive monthly censuses of WGS and FS within a 11.3 ha section of the California Botanic Garden. Variation in the numbers for both species and their synchrony was distributed across long timescales (>15 months).
3. After filtering out annual changes, concurrent mean monthly temperatures from nearby Ontario Airport yielded a spectrum with a large semi‐annual peak and significant spectral power at long timescales (>28 months). The cospectrum between WGS numbers and temperature revealed a significant negative correlation at long timescales (>35 months). Cospectra also revealed significant negative correlations with temperature at a six‐month timescale for both WGS and FS.
4. Simulations from a model of two competing species indicate that the risk of extinction for the weaker competitor increases quickly as environmental noise shifts from short to long timescales.
5. We analyzed the timescales of fluctuations in detrended mean annual temperatures for the time period 1915–2014 from 1218 locations across the continental USA. In the last two decades, significant shifts from short to long timescales have occurred, from <3 years to 4–6 years.
6. Our results indicate that (i) population fluctuations in co‐occurring native and invasive tree squirrels are synchronous, occur over long timescales, and may be driven by fluctuations in environmental conditions; (ii) long timescale population fluctuations increase the risk of extinction in competing species, especially for the inferior competitor; and (iii) the timescales of interannual environmental fluctuations may be increasing from recent historical values. These results have broad implications for the impact of climate change on the maintenance of biodiversity.

     

Partitioning controls on Amazon forest photosynthesis between environmental and biotic factors at hourly to interannual timescales

Gross ecosystem productivity (GEP) in tropical forests varies both with the environment and with biotic changes in photosynthetic infrastructure, but our understanding of the relative effects of these factors across timescales is limited. Here, we used a statistical model to partition the variability of seven years of eddy covariance‐derived GEP in a central Amazon evergreen forest into two main causes: variation in environmental drivers (solar radiation, diffuse light fraction, and vapor pressure deficit) that interact with model parameters that govern photosynthesis and biotic variation in canopy photosynthetic light‐use efficiency associated with changes in the parameters themselves. Our fitted model was able to explain most of the variability in GEP at hourly (R² = 0.77) to interannual (R² = 0.80) timescales. At hourly timescales, we found that 75% of observed GEP variability could be attributed to environmental variability. When aggregating GEP to the longer timescales (daily, monthly, and yearly), however, environmental variation explained progressively less GEP variability: At monthly timescales, it explained only 3%, much less than biotic variation in canopy photosynthetic light‐use efficiency, which accounted for 63%. These results challenge modeling approaches that assume GEP is primarily controlled by the environment at both short and long timescales. Our approach distinguishing biotic from environmental variability can help to resolve debates about environmental limitations to tropical forest photosynthesis. For example, we found that biotically regulated canopy photosynthetic light‐use efficiency (associated with leaf phenology) increased with sunlight during dry seasons (consistent with light but not water limitation of canopy development) but that realized GEP was nonetheless lower relative to its potential efficiency during dry than wet seasons (consistent with water limitation of photosynthesis in given assemblages of leaves). This work highlights the importance of accounting for differential regulation of GEP at different timescales and of identifying the underlying feedbacks and adaptive mechanisms.     

Stochastic flowering phenology in Dactylis glomerata populations described by Markov chain modelling

Understanding the relationship between flowering patterns and pollen dispersal is important in climate change modelling, pollen forecasting, forestry and agriculture. Enhanced understanding of this connection can be gained through detailed spatial and temporal flowering observations on a population level, combined with modelling simulating the dynamics. Species with large distribution ranges, long flowering seasons, high pollen production and naturally large populations can be used to illustrate these dynamics. Revealing and simulating species-specific demographic and stochastic elements in the flowering process will likely be important in determining when pollen release is likely to happen in flowering plants. Spatial and temporal dynamics of eight populations of Dactylis glomerata were collected over the course of two years to determine high-resolution demographic elements. Stochastic elements were accounted for using Markov chain approaches in order to evaluate tiller-specific contribution to overall population dynamics. Tiller-specific developmental dynamics were evaluated using three different RV matrix correlation coefficients. We found that the demographic patterns in population development were the same for all populations with key phenological events differing only by a few days over the course of the seasons. Many tillers transitioned very quickly from non-flowering to full flowering, a process that can be replicated with Markov chain modelling. Our novel approach demonstrates the identification and quantification of stochastic elements in the flowering process of D. glomerata, an element likely to be found in many flowering plants. The stochastic modelling approach can be used to develop detailed pollen release models for Dactylis, other grass species and probably other flowering plants.

     

Genetically idiosyncratic responses of Drosophila melanogaster populations to selection for improved learning ability

To what extent is adaptive evolution over short timescales repeatable? To address this question, we studied the performance of crosses between replicate Drosophila melanogaster lines previously subject to selection for improved learning response in the context of oviposition substrate choice. Of the 10 pairwise F₁ crosses among the five selection lines, four performed in the original learning assay similarly to the parental lines, whereas the remaining six showed learning scores significantly below the average of the parental lines. In particular, four F₁ crosses (three involving the same line) showed no detectable learning, on a par with unselected control lines. This indicates that the response to selection in some lines involved allelic substitutions at different loci. Additional assays of crosses between two selection lines indicated that the loss of performance in hybrids generalized to another type of learning assay, and held for both short‐ and long‐term memory. Joint analysis of first‐ and second‐generation crosses between these two lines supported the hypothesis that the response to selection in these different lines was based on the spread of recessive alleles at different loci. These results show that the evolutionary trajectories of populations of the same origin subject to uniform selection may sometimes diverge over very short evolutionary timescales.     

Covariance structure in the skull of Catarrhini: a case of pattern stasis and magnitude evolution

The study of the genetic variance/covariance matrix (G-matrix) is a recent and fruitful approach in evolutionary biology, providing a window of investigating for the evolution of complex characters. Although G-matrix studies were originally conducted for microevolutionary timescales, they could be extrapolated to macroevolution as long as the G-matrix remains relatively constant, or proportional, along the period of interest. A promising approach to investigating the constancy of G-matrices is to compare their phenotypic counterparts (P-matrices) in a large group of related species; if significant similarity is found among several taxa, it is very likely that the underlying G-matrices are also equivalent. Here we study the similarity of covariance and correlation structure in a broad sample of Old World monkeys and apes (Catarrhini). We made phylogenetically structured comparisons of correlation and covariance matrices derived from 39 skull traits, ranging from between species to the superfamily level. We also compared the overall magnitude of integration between skull traits (r²) for all Catarrhini genera. Our results show that P-matrices were not strictly constant among catarrhines, but the amount of divergence observed among taxa was generally low. There was significant and positive correlation between the amount of divergence in correlation and covariance patterns among the 30 genera and their phylogenetic distances derived from a recently proposed phylogenetic hypothesis. Our data demonstrate that the P-matrices remained relatively similar along the evolutionary history of catarrhines, and comparisons with the G-matrix available for a New World monkey genus (Saguinus) suggests that the same holds for all anthropoids. The magnitude of integration, in contrast, varied considerably among genera, indicating that evolution of the magnitude, rather than the pattern of inter-trait correlations, might have played an important role in the diversification of the catarrhine skull.     

Models of Monoamine Oxidase A and B Active Sites Obtained by using 3D QSAR with CoMFA Analysis

Abstract

The monoamine oxidase catalyses the oxidative deamination of neuroactive amines. This enzyme exists in two forms A and B, which differ by substrates preference and inhibitors specificity. Investigation of the structures of these enzymes and design new selective inhibitors are of greatly interesting since MAO A inhibitors are used in therapeutic practice as antidepressants and MAO B inhibitors – in the treatment Parkinson's diseases. The three dimension structures of monoamine oxidases are still unknown. Therefore, one of the most perspective approach to define significant features of structure active site is method based on analysis of structure-activity relationship (3D QSAR) with comparison of molecular fields analysis (CoMFA) allowing to get the spatial distribution of important properties affecting the activity.

In present study we investigate the structures of active sites MAO A and B using 16 pyrazinocarbazole derivatives in variant conformation. Majority of pyrazinocarbazole derivatives have a rigit conformation, but three of those is sufficiently flexible. The latters can be in two conformation types: long molecules (substitution accommodate along axis of main structure) and short molecules (substitution accommodate at acute angle about of main structure). Several 3D QSAR and CoMFA models of MAO A and B active sites were design for data sets containing various types of flexible molecules conformation. All obtained models are statistical reliable and have sufficient predictive power for tested compound tetrindole. The best MAO A model that include two flexible molecules in long conformations was obtained, and the longest one of those in short conformation. In contrast, for MAO B model containing all flexible molecules in the short conformations is more preferred.

On the basis of obtained data the schematic models of MAO A and B active sites structures are proposed. According to these models MAO A active site have the narrow long cavity that accommodate long molecules, while MAO B active site is broader and shorter.     

Pollination,mating and reproductive fitness in a plant population with bimodal floral‐tube length

Mating patterns and natural selection play important roles in determining whether genetic polymorphisms are maintained or lost. Here, we document an atypical population of Lapeirousia anceps (Iridaceae) with a bimodal distribution of floral‐tube length and investigate the reproductive mechanisms associated with this pattern of variation. Flowers were visited exclusively by the long‐proboscid fly Moegistorhynchus longirostris (Nemestrinidae), which exhibited a unimodal distribution of proboscis length and displayed a preference for long‐tubed phenotypes. Despite being visited by a single pollinator species, allozyme markers revealed significant genetic differentiation between open‐pollinated progeny of long‐ and short‐tubed phenotypes suggesting mating barriers between them. We obtained direct evidence for mating barriers between the floral‐tube phenotypes through observations of pollinator foraging, controlled hand pollinations and measurements of pollen competition and seed set. Intermediate tube‐length phenotypes produced fewer seeds in the field than either long‐ or short‐tubed phenotypes. Although floral‐tube length bimodality may not be a stable state over long timescales, reproductive barriers to mating and low ‘hybrid’ fitness have the potential to contribute to the maintenance of this state in the short term.     

Drawing from Memory: Hand-Eye Coordination at Multiple Scales

Eyes move to gather visual information for the purpose of guiding behavior. This guidance takes the form of perceptual-motor interactions on short timescales for behaviors like locomotion and hand-eye coordination. More complex behaviors require perceptual-motor interactions on longer timescales mediated by memory, such as navigation, or designing and building artifacts. In the present study, the task of sketching images of natural scenes from memory was used to examine and compare perceptual-motor interactions on shorter and longer timescales. Eye and pen trajectories were found to be coordinated in time on shorter timescales during drawing, and also on longer timescales spanning study and drawing periods. The latter type of coordination was found by developing a purely spatial analysis that yielded measures of similarity between images, eye trajectories, and pen trajectories. These results challenge the notion that coordination only unfolds on short timescales. Rather, the task of drawing from memory evokes perceptual-motor encodings of visual images that preserve coarse-grained spatial information over relatively long timescales as well.     

Formation of the function of the photosensing system in early development

The function of simple eyes in two planarian species, two-eyed Girardia tigrina and multi-eyed Polycelis tenuis, has been studied. When exposed to light, planarians display a light avoidance reaction known as negative phototaxis. This reaction has been investigated in intact animals and in head and tail fragments in the course of eye regeneration after their section. Specific features of the phototaxis reaction have been described in all groups of animals. The differences in light response recovery were shown between two planarian species and two regenerating fragments. No correlation has been found between phototactic reactions and restoration of eye structure, the number of eyes, maturation of the ganglion, growth of regenerative blastema, and motor system. The phototactic response occurred two days after the recovery of the morphology of eyes and their connection with the brain. The participation of conserved and novel genes in early development of the eye function is discussed.     

High‐ and low‐frequency mechanical properties of living starfish oocytes

We studied the mechanical properties of living starfish oocytes belonging to two species, Astropecten Auranciacus and Asterina pectinifera, over a wide range of timescales. We monitored the Brownian motion of microspheres injected in the cytoplasm using laser particle‐tracking (LPT) and video multiple‐particle‐tracking (MPT) techniques, to explore high‐ and low‐frequency response ranges, respectively. The analysis of the mean‐square‐displacements (MSD) allowed us to characterize the samples on different timescales. The MSD behavior is explained by three power‐law exponents: for short times (τ < 1 ms) it reflects the semiflexible behavior of the actin network; for intermediate timescales (1 ms < τ < 1 s) it is similar to that of a soft‐glass material; finally for long times (τ > 1 s) it behaves mainly like a viscous medium. We computed and compared the viscoelastic moduli using a recently proposed model describing the frequency response of the cell material. The large fluctuations found in the MSD over hundreds of trajectories indicate and confirm the significant cytoplasm heterogeneity. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Recovery of plains rough fescue grasslands on reclaimed well sites

Plains rough fescue (Festuca hallii), once dominant in grasslands of the Northern Great Plains, has been reduced to remnants mainly through agricultural and energy sector development. This study assessed the impacts of oil and gas well site disturbances on plains rough fescue grassland to predict successional trends following disturbance. We examined trends in vegetation cover, richness, diversity, and community composition for two construction techniques (topsoil stripping, minimum disturbance), three revegetation methods (agronomic seed mix, native seed mix, natural recovery), and two reclamation scenarios (reclaimed within < 10 yrs; reclaimed within > 10 yrs) relative to adjacent undisturbed prairie (reference sites) over 28 years in 33 grassland sites. Reclamation success was more closely related to methods of construction and revegetation than years since reclamation. Species richness, diversity, both native and non-native species cover, and species composition were similar between undisturbed prairie and areas subject to minimum disturbance and natural recovery. In contrast, undisturbed prairie differed from areas with topsoil stripping and seeding to either agronomic or native species. Plant community composition on minimum disturbance sites with natural recovery was returning to a predisturbed plains rough fescue community within 10 years after reclamation. Impacts of construction method that involved intensive soil handling and seeding with native or non-native seed mixes were disruptive to recovery of fescue grassland. We therefore recommend retaining grassland sod intact through minimum disturbance and utilizing natural recovery as the best option for successful reclamation of native rough fescue grassland after well site disturbance.     

Neural Substrates Related to Motor Memory with Multiple Timescales in Sensorimotor Adaptation

Recent computational and behavioral studies suggest that motor adaptation results from the update of multiple memories with different timescales. Here, we designed a model-based functional magnetic resonance imaging (fMRI) experiment in which subjects adapted to two opposing visuomotor rotations. A computational model of motor adaptation with multiple memories was fitted to the behavioral data to generate time-varying regressors of brain activity. We identified regional specificity to timescales: in particular, the activity in the inferior parietal region and in the anterior-medial cerebellum was associated with memories for intermediate and long timescales, respectively. A sparse singular value decomposition analysis of variability in specificities to timescales over the brain identified four components, two fast, one middle, and one slow, each associated with different brain networks. Finally, a multivariate decoding analysis showed that activity patterns in the anterior-medial cerebellum progressively represented the two rotations. Our results support the existence of brain regions associated with multiple timescales in adaptation and a role of the cerebellum in storing multiple internal models.     

The Spatial Structure of Stimuli Shapes the Timescale of Correlations in Population Spiking Activity

Throughout the central nervous system, the timescale over which pairs of neural spike trains are correlated is shaped by stimulus structure and behavioral context. Such shaping is thought to underlie important changes in the neural code, but the neural circuitry responsible is largely unknown. In this study, we investigate a stimulus-induced shaping of pairwise spike train correlations in the electrosensory system of weakly electric fish. Simultaneous single unit recordings of principal electrosensory cells show that an increase in the spatial extent of stimuli increases correlations at short () timescales while simultaneously reducing correlations at long () timescales. A spiking network model of the first two stages of electrosensory processing replicates this correlation shaping, under the assumptions that spatially broad stimuli both saturate feedforward afferent input and recruit an open-loop inhibitory feedback pathway. Our model predictions are experimentally verified using both the natural heterogeneity of the electrosensory system and pharmacological blockade of descending feedback projections. For weak stimuli, linear response analysis of the spiking network shows that the reduction of long timescale correlation for spatially broad stimuli is similar to correlation cancellation mechanisms previously suggested to be operative in mammalian cortex. The mechanism for correlation shaping supports population-level filtering of irrelevant distractor stimuli, thereby enhancing the population response to relevant prey and conspecific communication inputs.     

Sensitivity-based adaptive mesh refinement collocation method for dynamic optimization of chemical and biochemical processes

Collocation on finite element (CFE) is an effective simultaneous method of dynamic optimization to increase the profitability or productivity of industrial process. The approach needs to select an optimal mesh of time interval to balance the computational cost with desired solution. A new CFE approach with non-uniform refinement procedure based on the sensitivity analysis for dynamic optimization problems is, therefore, proposed, where a subinterval is further refined if the obtained control parameters have significant effect on the performance index. To improve the efficiency, the sensitivities of state parameters with respect to control parameters are derived from the solution of the discretized dynamic system. The proposed method is illustrated by testing two classic dynamic optimization problems from chemical and biochemical engineering. The detailed comparisons among the proposed method, the CFE with uniform mesh, and other reported methods are also carried out. The research results reveal the effectiveness of the proposed approach.

     

Testing the short-term effects of a fish invader on the trophic ecology of a closely related species

The effects of invaders on native species are usually tested using species mean trait values over long time scales. However, considering individual variation over short timescales can help us better understand the interaction between invaders and native species. We compared trophic traits of the non-native guppy (Poecilia reticulata) and the native Brazilian poeciliid Phalloceros harpagos using experiments simulating the early stages of an invasive process. We used short-term mesocosms to simulate an early invasion scenario, where the two species were placed together, and a pre-invasion scenario, where species were kept separated, and analyzed interspecific and intraspecific trophic variability. We also compared the foraging efficiency of species in laboratory experiments. We found no differences on the mean diet of both species between pre and early invasion treatments. At the individual level, in the early invasion scenario, individuals of both species reduced their trophic niche as a probable effect of the presence of the heterospecific. Phalloceros harpagos had higher consumption rates than guppies indicating greater efficiency in feeding on invertebrates. Our results suggest that non-native species were not intrinsically better consumers of high-quality resources. Instead, intraspecific variation might be playing an overlooked role in shaping interactions between species during the early stages of invasion.

     

Do warmer growing seasons ameliorate the recovery of mountain birches after winter moth outbreak?

Subarctic mountain birch (Betula pubescens ssp. czerepanovii) forests in northern Fennoscandia have shown a slight recovery from recent severe defoliation by the winter moth (Operophtera brumata). This development in trees is hypothesized to be a result of ameliorated growing conditions through increased summer temperatures. We examined if accumulated thermal sum affects the ability of mountain birches to tolerate foliage losses. We quantified the number of leaf-bearing short shoots, the emergence of inflorescences and the seasonal height growth of long shoots in both intact and defoliated trees. We also determined the concentrations of carbon and nitrogen in leaves and carbohydrates in roots. Our results show that defoliation constrained the growth of long shoots, as well as the emergence of inflorescences regardless of thermal sum accumulation. However, the number of leaf-bearing short shoots did not differ between intact and defoliated trees. In the both tree groups, the amounts of emerging leaves increased as a response to thermal sum accumulation. Also the leaf carbon concentration increased in defoliated trees at higher thermal sums, whereas it decreased in intact controls. Generally, the mean carbohydrate concentrations were greater in roots of defoliated than intact trees. However, with increased thermal sums, root carbohydrates increased in intact trees but remained the same in defoliated trees. We conclude that thermal sum accumulation does not greatly promote the recovery of mountain birches. Although the damaged trees produced more leaves at warmer growing sites, this did not increase their height growth or carbohydrate gain in roots.     

Computational annotation of plant metabolomics profiles via a novel network-assisted approach

Mass spectrometry (MS) has become the analytical method of choice in plant metabolomics. Nevertheless, metabolite annotation remains a major challenge and implies the integration of structural searches in compound libraries with biological knowledge inferred from metabolite regulation studies. Here we propose a novel integrative approach to process and exploit the rich structural information contained in in-source fragmentation patterns of high-resolution LC–MS profiles. In this approach, a correlation matrix is first calculated from individual mass features extracted by xcms processing. Mass feature co-regulation patterns corresponding to metabolite in-source fragmentation are then detected and assembled into compound spectra using the R package CAMERA and processed for in silico fragment-based structure elucidation using MetFrag. We validate the performance of this approach for the rapid annotation of the twelve largest compound spectra, including four O-acyl sugars and six 17-hydroxygeranyllinalool diterpene glycosides in metabolic profiles of insect-attacked Nicotiana attenuata leaves. Additionally, we demonstrate the power of refining MetFrag metabolite annotations based on co-regulation patterns between known and unknown compounds in the correlation matrix and proposed structural annotations on two previously un-characterized O-acyl sugars. In summary, this novel approach facilitates compound annotation from in-source fragmentation patterns using correlation between intensities of mass features of one or several metabolites. Additionally, this analysis provides further support that insect herbivory activates major metabolic reconfigurations in N. attenuata leaves.     

Effect of time during transport of excised mare ovaries on oocyte recovery rate and quality after in vitro maturation

In the mare only a limited number of oocytes can be successfully collected in vivo, so that when large numbers of oocytes are needed for experimentation, ovaries harvested from slaughtered mares must be used. The resulting temperature changes and time intervals mandated by handling and transport of ovaries from the slaughterhouse to the laboratory adversely affect the rate of oocyte recovery and their quality after IVF and maturation. We chose to study the effect of temperature and time in transit of excised ovaries by evaluating rate of oocyte recovery, nuclear maturation stage reached before, and cleavage rate reached after IVF, following short (1.5 to 4 h) and long (6 to 8 h) storage. Temperatures in the storage container decreased from 37-C to 32 degrees and 27.5 degrees C during the short and long interval, respectively. The cumulus-oocytes complexes (COCs) were classified as having a compact cumulus, completely or partially surrounding the oocyte (compact); those having only a corona radiata surrounding the oocyte (corona); those having a completely or partially expanded cumulus, showing a cellular or sparsely cellular, gelatinous cloud around the oocyte (expanded); and those that were completely denuded of both cumulus and corona cells (denuded). All COCs, except the denuded ones, which were discarded, were matured in vitro for 30 h at 38.5 degrees C in 5% CO2. The recovery rate of oocytes was significantly higher after long vs short storage (48 vs 35%; P < 0.01), but the distribution of the collected COCs into the 4 classes was not affected by the storage time. After in vitro maturation nuclear maturity was not affected by the storage time, but oocytes with intact cytoplasmic membranes were more frequently found after short than after long storage (54 vs 34%; P = 0.07), and fully matured oocytes were more often seen with intact membrane (P < 0.01). Moreover, oocytes with intact membranes in metaphase II (MII) were associated with short storage intervals and the corona COC class, while damaged membranes and incomplete maturation were associated with the long storage and the compact COC class.     

Serological characterization of human reassortant rotaviruses.

We analyzed the serological properties of two human wild-type cell culture-adapted rotaviruses (strains 308 and 46) and of 308 X 46 reassortants which were previously obtained and genetically characterized. Strain 308, exhibiting a so-called long RNA pattern, was found to belong to human rotavirus subgroup II, serotype 1, whereas strain 46, exhibiting a so-called short RNA pattern, represented subgroup I, serotype 2. Among the 308 X 46 reassortants we analyzed, two belonged to subgroup II, serotype 1, and exhibited short RNA patterns. This showed that the correlation observed between human subgroups I and II rotaviruses and the short and long electrophoretic patterns is not supported by any molecular basis (i.e., gene segment 10 or 11 was not involved in the subgroup specificity).