Changes In Microenvironmental Conditions Research Articles

Transcriptomic profiling of the development of the inflammatory response in human monocytes in vitro.

Monocytes/macrophages are key players in all phases of physiological and pathological inflammation. To understanding the regulation of macrophage functional differentiation during inflammation, we designed an in vitro model that recapitulates the different phases of the reaction (recruitment, initiation, development, and resolution), based on human primary blood monocytes exposed to sequential changes in microenvironmental conditions. All reaction phases were profiled by transcriptomic microarray analysis. Distinct clusters of genes were identified that are differentially regulated through the different phases of inflammation. The gene sets defined by GSEA analysis revealed that the inflammatory phase was enriched in inflammatory pathways, while the resolution phase comprised pathways related to metabolism and gene rearrangement. By comparing gene clusters differentially expressed in monocytes vs. M1 and vs. M2 macrophages extracted from an in-house created meta-database, it was shown that cells in the model resemble M1 during the inflammatory phase and M2 during resolution. The validation of inflammatory and transcriptional factors by qPCR and ELISA confirmed the transcriptomic profiles in the different phases of inflammation. The accurate description of the development of the human inflammatory reaction provided by this in vitro kinetic model can help in identifying regulatory mechanisms in physiological conditions and during pathological derangements.

Intratumor heterogeneity: Nature and biological significance

Intratumor heterogeneity inherent in the majority of human cancers is a major obstacle for a highly efficient diagnosis and successful prognosis and treatment of these diseases. Being a result of clonal diversity within the same tumor, intratumor heterogeneity can be manifested in variability of genetic and epigenetic status, gene and protein expression, morphological structure, and other features of the tumor. It is most likely that the appearance of this diversity is a source for the adaptation of the tumor to changes in microenvironmental conditions and/or a tool for changing its malignant potential. In any case, both processes result in the appearance of cell clones with different undetermined sets of hallmarks. In this review, we describe the heterogeneity of molecular disorders in various human tumors and consider modern viewpoints of its development including genetic and non-genetic factors of heterogeneity origin and the role of cancer stem cells and clonal evolution. We also systematize data on the contribution of tumor diversity to progression of various tumors and the efficiency of their treatment. The main problems are indicated in the diagnosis and therapy of malignant tumors caused by intratumor heterogeneity and possible pathways for their solution. Moreover, we also suggest the key goals whose achievement promises to minimize the problem of intratumor heterogeneity and to identify new prognostic, predictive, and target markers for adequate and effective treatment of cancer.

The influence of tree species mixture on ecosystem-level carbon accumulation and water use in a mixed boreal plantation

Throughout the world, huge areas have been occupied by monospecific tree plantations in order to fulfil the increasing demand for industrial wood products. The use of mixed-species plantations has recently been advocated as a potential compromise between maintaining high-volume wood production and conserving other ecosystem services. Yet little is known about the impact of tree species mixture on species- and ecosystem-level carbon accumulation and water use in mixed plantations. We combined data on above-ground biomass, xylem sap flux density, and the carbon and oxygen isotope composition of leaves and needles in a boreal plantation to test whether different levels of species mixture would impact tree- and plot-level biomass production, transpiration and water use efficiency. Data were recorded in 22 20-x-20-m plots (7 for transpiration) randomly allocated to either monocultures or to two-, three-, and five-species mixtures of Scots pine (Pinus sylvestris), Norway spruce (Picea abies), Silver birch (Betula pendula), Common alder (Alnus glutinosa) and Siberian larch (Larix sibirica). At tree level, for a given species, we found significant differences among mixtures in transpiration and water use efficiency, though species mixture had no impact on above-ground biomass. At plot level, a large variability in functioning among mixtures was observed, but increasing the number of species in the mixture did not enhance productivity, transpiration or water use efficiency. The presence in mixtures of a high performing species like birch brought about changes in the canopy structure which in turn may have led to changes in micro-environmental conditions. Such changes could have contributed to explain differences in transpiration and water use efficiency among mixtures. We concluded that mixing locally-adapted species under non-limiting soil water conditions did not provide any benefit for ecosystem-level carbon accumulation and water use at this young ontogenic stage, but our study does not preclude that some benefits might arise at older stages.

Lichen-induced biomodification of calcareous surfaces: Bioprotection versus biodeterioration

Studies demonstrate the active and passive capability of lichens to inhibit or retard the weathering of calcareous surfaces. Lichen coverage may actively protect a surface through shielding by the thallus and the binding and waterproofing of the rock surface and subsurface by fungal hyphae. Passive protection of rock surfaces may be induced by the formation of an insoluble encrustation, such as calcium oxalate, at the lichen-rock interface. Recent research suggests that the decay of hyphae, induced by changes in microenvironmental conditions, necrosis, parasitism or the natural physiological traits of particular lichen species, may expose a chemically and physically weakened substrate to dissolution, triggering relatively rapid weathering-related surface lowering. Consequently, certain epilithic crustose and endolithic lichens may induce a period of surface stability throughout the course of their lifespan, followed by a phase of instability and rapid episodic microtopographical evolution after death and decay. A series of conceptual models is proposed to illustrate this idea over short (single lichen lifespan) and long (multiple lichen lifespans) timescales. The models suggest that the microscale biogeomorphological system of lichen-rock interaction is underpinned by non-linear dynamical system theory as it exhibits dynamical instability and is consequently difficult to predict over a long timescale. Dominance by biodeterioration or bioprotection may be altered by changes in lichen species or in environmental conditions over time.

Cell mass and cell cycle dynamics of an asynchronous budding yeast population: Experimental observations, flow cytometry data analysis, and multi‐scale modeling

Despite traditionally regarded as identical, cells in a microbial cultivation present a distribution of phenotypic traits, forming a heterogeneous cell population. Moreover, the degree of heterogeneity is notably enhanced by changes in micro-environmental conditions. A major development in experimental single-cell studies has taken place in the last decades. It has however not been fully accompanied by similar contributions within data analysis and mathematical modeling. Indeed, literature reporting, for example, quantitative analyses of experimental single-cell observations and validation of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical description of the dynamics of cell size and cell cycle position distributions, of a population of Saccharomyces cerevisiae, in response to the substrate consumption observed during batch cultivation. The good agreement between the proposed multi-scale model (a population balance model [PBM] coupled to an unstructured model) and experimental data (both the overall physiology and cell size and cell cycle distributions) indicates that a mechanistic model is a suitable tool for describing the microbial population dynamics in a bioreactor. This study therefore contributes towards the understanding of the development of heterogeneous populations during microbial cultivations. More generally, it consists of a step towards a paradigm change in the study and description of cell cultivations, where average cell behaviors observed experimentally now are interpreted as a potential joint result of various co-existing single-cell behaviors, rather than a unique response common to all cells in the cultivation.

Cell lineage analysis of acute leukemia relapse uncovers the role of replication-rate heterogeneity and microsatellite instability

AbstractHuman cancers display substantial intratumoral genetic heterogeneity, which facilitates tumor survival under changing microenvironmental conditions. Tumor substructure and its effect on disease progression and relapse are incompletely understood. In the present study, a high-throughput method that uses neutral somatic mutations accumulated in individual cells to reconstruct cell lineage trees was applied to hundreds of cells of human acute leukemia harvested from multiple patients at diagnosis and at relapse. The reconstructed cell lineage trees of patients with acute myeloid leukemia showed that leukemia cells at relapse were shallow (divide rarely) compared with cells at diagnosis and were closely related to their stem cell subpopulation, implying that in these instances relapse might have originated from rarely dividing stem cells. In contrast, among patients with acute lymphoid leukemia, no differences in cell depth were observed between diagnosis and relapse. In one case of chronic myeloid leukemia, at blast crisis, most of the cells at relapse were mismatch-repair deficient. In almost all leukemia cases, > 1 lineage was observed at relapse, indicating that diverse mechanisms can promote relapse in the same patient. In conclusion, diverse relapse mechanisms can be observed by systematic reconstruction of cell lineage trees of patients with leukemia.

Space warping order parameters and symmetry: application to multiscale simulation of macromolecular assemblies.

Coarse-grained features of macromolecular assemblies are understood via a set of order parameters (OPs) constructed in terms of their all-atom configuration. OPs are shown to be slowly changing in time and capture the large-scale spatial features of macromolecular assemblies. The relationship of these variables to the classic notion of OPs based on symmetry breaking phase transitions is discussed. OPs based on space warping transformations are analyzed in detail as they naturally provide a connection between overall structure of an assembly and all-atom configuration. These OPs serve as the basis of a multiscale analysis that yields Langevin equations for OP dynamics. In this context, the characteristics of OPs and PCA modes are compared. The OPs enable efficient all-atom multiscale simulations of the dynamics of macromolecular assemblies in response to changes in microenvironmental conditions, as demonstrated on the structural transitions of cowpea chlorotic mottle virus capsid (CCMV) and RNA of the satellite tobacco mosaic virus (STMV).

Overlapping defense responses to water limitation and pathogen attack and their consequences for resistance to powdery mildew disease in garlic mustard, Alliaria petiolata

Plant responses to abiotic stress can alter their response to biotic stress. We examined changes in the activity of several defense proteins in response to powdery mildew infection of garlic mustard (Alliaria petiolata) in the greenhouse and in the field. Second, we examined the effects of water limitation on the same defense protein responses, as well as on total soluble protein and glucose concentration, plant growth, and powdery mildew disease development. Similar increases in the activity of peroxidase, chitinase, and β-1-3-glucanase were observed in leaves of plants with substantial powdery mildew disease in both greenhouse- and field-grown plants. In the greenhouse, activities of chitinase and peroxidase as well as total soluble protein and glucose concentrations generally increased with the degree of water limitation. In turn, leaf growth and powdery mildew symptom development decreased as the degree of water limitation increased. This study revealed that plant chemical responses to water limitation and powdery mildew disease can overlap to a large extent, which, in addition to changing microenvironmental conditions and other indicators of plant quality, may underlie the ability of water limitation to inhibit powdery mildew disease symptom development in this wild plant pathosystem.

The immunohistochemistry of invasive and proliferative phenotype switching in melanoma: a case report

To date there is no effective therapy for metastatic melanoma and at the molecular level the disease progression is poorly understood. A recent study by our group led to the development of a novel phenotype switching model for melanoma progression, wherein cells transition back-and-forth between states of proliferation and invasion to drive disease progression. To explore the model's clinical relevance we interrogated phenotype-specific expression patterns in human melanoma patient material. A matched primary/metastasis pair from a human melanoma patient was obtained and immunohistochemically stained for proliferative and invasive phenotype markers. These were also stained for hypoxia and blood vessel markers. Proliferative phenotype markers Melan-A and Mitf showed consistent anti-correlation with invasive phenotype marker Wnt5A and hypoxia marker Glut-1. These also correlated with observed intra-tumoural vascularization patterns. Similar pattern distributions were present in both primary and metastasis samples. Strikingly, we observed that late phase metastatic melanoma cells adopt morphologies and behaviours identical to very early phase cells. The expression patterns observed closely matched expectations derived from previous in vitro and xenografting experiments. These results highlight the likelihood that disease progression involves melanoma cells retaining the capacity to regulate the expression of metastatic potential critical factors according to changing microenvironmental conditions.

Micro-environmental change as a trigger for granite decay in offshore Irish lighthouses: implications for the long-term preservation of operational historic buildings

Following automation of lighthouses around the coastline of Ireland, reports of accelerated deterioration of interior granite stonework have increased significantly with an associated deterioration in the historic structure and rise in related maintenance costs. Decay of granite stonework primarily occurs through granular disintegration with the effective grusification of granite surfaces. A decay gradient exists within the towers whereby the condition of granite in the lower levels is much worse than elsewhere. The lower tower levels are also regions with highest relative humidity values and greatest salt concentrations. Data indicate that post-automation decay may have been triggered by a change in micro-environmental conditions within the towers associated with increased episodes of condensation on stone surfaces. This in turn appears to have facilitated deposition and accumulation of hygroscopic salts (e.g. NaCl) giving rise to widespread evidence of deliquescence in the lower tower levels. Evidence indicates that the main factors contributing to accelerated deterioration of interior granite stonework are changes in micro-environmental conditions, salt weathering, chemical weathering through the corrosive effect of strongly alkaline conditions on alumino-silicate minerals within the granite and finally, the mica-rich characteristics of the granite itself which increases its structural and chemical susceptibility to subaerial weathering processes by creating points of weakness within the granite. This case study demonstrates how seemingly minor changes in micro-environmental conditions can unintentionally trigger the rapid and extensive deterioration of a previously stable rock type and threaten the long-term future of nationally iconic operational historic structures.

Influence of Thinning on Soil CO 2 Efflux in Chinemse Fir Plantations

ABSTRACT Forest management is expected to influence soil CO 2 efflux ( F CO 2 ) as a result of changes in microenvironmental conditions, soil microclimate, and root dynamics. Soil F CO 2 rate was measured during the growing season of 2006 in both thinning and non-thinning locations within stands ranging from 0 to 8 years after the most recent thinning in Chinese fir ( Cunninghamia lanceolata (Lamb.) Hook) plantations in Huitong Ecosystem Research Station, Hunan, China. Soil temperature and moisture were also measured to examine relationships between F CO 2 and soil properties. Forest thinning resulted in huge changes in F CO 2 that varied with time since cutting. Immediately following harvest (year 0) F CO 2 in thinning area increased by about 30%, declined to 20%–27% below pre-cutting levels during years 4–6, and recovered to pre-cutting levels at 8 years post-cutting. A similar temporal pattern, but with smaller changes, was found in non-thinning locations. The initial increase in F CO 2 could be attributed to a combination of root decay, soil disturbance, and increased soil temperature in gaps, while the subsequent decrease and recovery to the death and gradual regrowth of active roots. Strong effects of soil temperature and soil water content on F CO 2 were found. Forest thinning mainly influenced F CO 2 through changes in tree root respiration, and the net result was a decrease in integrated F CO 2 flux through the entire felling cycle.

Colonization and decomposition of salal (Gaultheria shallon) leaf litter by saprobic fungi in successional forests on coastal British Columbia

The colonization of leaf litter by saprobic fungi was studied in old-growth and post-harvest successional Douglas-fir forests on southeast Vancouver Island, British Columbia. This study focused on leaf litter of salal (Gaultheria shallon Pursh.), a dominant understory shrub in all stands. Salal litter is characterized by the occurrence of bleached portions attributable to fungal colonization of the litter and to the variable decomposition of recalcitrant compounds, such as lignin. Analyses of proximate chemical fractions, fungal assemblages on the bleached leaf area, and pure culture decomposition assays indicated that Marasmius sp. and Coccomyces sp. were responsible for rapid decomposition and bleaching of salal leaf litter. The bleached area accounted for 17%-22% of total area of salal leaf litter collected in immature (40-60 years old), mature (85-105 years old), and old-growth (more than 290 years old) stands, but for only 2% in regeneration (5-15 years old) stands. The reduction of bleached leaf area occupied by Marasmius sp. and Coccomyces sp. in regeneration stands could be due to the changes in microenvironmental conditions on the forest floor, in litter quality, or in food-web structure in soils. The decrease of fungi able to decay recalcitrant compounds may lead to a reduction of salal decomposition rates in clear-cut sites that would persist until canopy closure occurs.

Isolation of intact RNA from cytometrically sorted Saccharomyces cerevisiae for the analysis of intrapopulation diversity of gene expression

Characterizing and understanding the functional heterogeneity in a given population on the cellular and molecular level is a great challenge in microbiology. Each microorganism contributes differently to the overall performance of the community and responds differently to changing microenvironmental conditions. Here, we present a method for isolation of intact RNA out of small subpopulations of live Saccharomyces cerevisiae cells for differential gene expression analysis. The protocol includes fluorescence staining, flow cytometric analysis and sorting of live yeast cells, subsequent isolation of RNA from the resulting subpopulations and finally RNA quantification and integrity check. The isolated RNA can be transcribed into cDNA and successfully used for microarray analysis. This aids in relating molecular regulation processes within subpopulations with the dynamics and functioning of the entire population. The procedure can be accomplished in 2 d.

The Concept of Mesenchymal Stem Cells

In this chapter we examine whether criteria usually defining adult tissue stem cells apply to mesenchymal stem cells (MSCs) that give rise to cells of the skeletal connective tissues. MSCs appear to constitute a heterogeneous population of undifferentiated and committed, lineage-primed cells, capable of: homing upon engraftment to a number of growth microenvironments, extensive proliferation, producing large numbers of differentiated progeny, and functional tissue repair after injury. In addition, MSCs are extensively distributed throughout tissues, and bone marrow MSCs provide the stromal component of the niche of hematopoietic stem cells. The capacity of apparently differentiated mesenchymal cells to shift their differentiation pathway with changing microenvironmental conditions (known as differentiation plasticity) may be due to de-differentiation and reprogramming in MSCs. Because they present several features setting them apart from other stem cells, MSCs may constitute another paradigm for stem cell systems, where self-renewal and hierarchy are no longer essential, but where plasticity is the major characteristic.

Size of Acer saccharum Hosts Does Not Influence Growth of Mature Bryophyte Gametophytes in Adirondack Northern Hardwood Forests

Several epiphytic bryophyte species (Anomodon attenuatus, Anomodon rugelii, Brachythecium oxycladon, Leucodon brachypus, Neckera pennata, Porella platyphylloidea, and Rauiella scita) have diminished frequencies of occurrence and abundances in second-growth and partially-cut Adirondack northern hardwood forests relative to old-growth forests. The occurrence and abundances of these species, all of which exhibit mesophytic growth forms and two of which (A. attenuatus and A. rugelii) are known calcicoles, are positively correlated with diameters of sugar maple (Acer saccharum) host trees. The mechanisms causing their specificity for large, old sugar maples hosts are not known, but their distributions may reflect interactions of their respective physiological tolerances with changing microenvironmental conditions on sugar maple bark as the host trees age and mature. We tested this “gradient in time” hypothesis by transplanting mature gametophyte mats on sugar maple trees ranging from 20–85 cm diameter at breast height. Furthermore, we tested this hypothesis at two sites, a mesic and a xeric forest stand, in order to assess the influences of meso-scale (stand-level) environmental factors on the micro-scale (individual tree-level) regulation of gametophyte growth. All but two of the 96 transplants remained alive after six years. Following an initial year of overall dieback, average cover increased 23% over the subsequent five year period. Tree diameter had no effect on expansion rates of any transplanted species. Only one species, Neckera pennata, exhibited significantly greater expansion at the mesic site than at the xeric site. Our data suggest that age-related changes in microenvironmental conditions of sugar maple bark do not have an important influence on the distribution of these “large-maple” epiphytes. Rather, factors such as dispersal limitations or establishment requirements of protonemata probably limit their distribution. Additional, well-replicated transplant experiments are required to determine the effects of micro- and meso-scale environmental variation on the establishment, growth, and reproduction of epiphytic bryophytes. We discuss implications of our results for restoration of epiphytic bryophyte communities in heavily disturbed forest landscapes.

Modelling the rapid retreat of building sandstones: a case study from a polluted maritime environment

Abstract Sandstones are widely used as building stones throughout NW Europe. Unlike limestone, sandstones tend to experience episodic and sometimes rapid surface retreat associated with the action of salts and often leading to the development of hollows/caverns in the stone. The unpredictability of these decay dynamics can present significant problems when planning conservation strategies. Consequently, successful conservation requires a better understanding of the factors that trigger decay and determine the subsequent decay pathway. An overview of results from previous studies provided the basis for simulation experiments aimed at identifying the factors that (a) initiate decay and (b) permit the continuance of salt weathering despite rapid loss of surface material. These simulation studies involve investigation of changes in micro-environmental conditions as surface hollows develop and examination of salt weathering dynamics within such hollows. These data combined with knowledge gained from previous work have allowed the refinement of a conceptual model of rapid sandstone retreat. In this model decay is linked to the establishment of positive feedback conditions through interactions between factors such as porosity, permeability, mineralogy and their effect on salt penetration.

Population dynamics ofImperata cylindrica (L.) Beauv. var. major related to slash and burn agriculture (jhum) in North Eastern India

Imperata cylindrica (L.) Beauv. var. major is an early successional weed coming up in abandoned fallows after slash and burn agriculture in the north-eastern hill region of India. This study is concerned with the population dynamics and reproductive potential of this species in successional communities. Natural regeneration through seeds occurred only in freshly burnt or cupped fallows though none of the seedlings survived. Natural regeneration was mainly through tillers which declined sharply in older fallows. As a result the species was completely eliminated in fallows older than 5 yrs. This pattern of behaviour of the species has been related to the changing micro-environmental conditions in the developing communities.