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PubMed2002

Use of simulation mass balance modeling to estimate phosphorus and bacteria dynamics in watersheds.

Dynamic simulation technology is integrated with mass balance concepts and compartment-flux diagramming to create computer models that estimate contaminant export from watersheds over long and short-term futures under alternative simulated policies of watershed management. The Watershed Ecosystem Nutrient Dynamics (WEND) model, applied to developed watersheds with a mix of urban, agricultural, and forest land-uses, predicted phosphorus (P) export from three watersheds; a 275,000 ha dairy/urban watershed, a 77,000 ha poultry/urban watershed, and a 23,000 ha swine dominated watershed. Urban, agricultural, and forestry activities contribute to P export in different proportions. In all cases the P imports to the watershed exceed total export and P accumulates in watershed soils. Long-term future P export patterns are compared for several watershed management strategies that range from encouragement of rapid urban growth to aggressive environmental protection. The specific response of each watershed to imposed management is unique, but management strategies designed to reduce export of P over the long-term need to consider options that promote P input/output balance. Using this same approach, the Watershed Ecosystem Bacterial Dynamics (WEBD) model assesses the dynamics of bacterial populations in a small case-study watershed over an annual cycle as influenced by dairy farm management actions. WEND and WEBD models integrate the diversity of activities and stakeholders interested in the watershed and promote development of a more holistic understanding of watershed function. Model outputs are designed to assist watershed policy-makers, managers, and planners to explore potential future impacts of management/policy decisions.

Agriculture↗
PubMedDate not supplied

Applications of time-resolved resonance energy transfer measurements in studies of the molecular crowding effect.

The native structures of many globular proteins are only weakly stabilized and form in solution ensembles of multiple conformers. The energy differences between the conformers are assumed to be small. This is the case of flexible multidomain proteins where domain motions were observed. High concentrations of inert macrosolute, which create a crowded or confined environment, can cause shifts of the distribution of the conformers of such proteins towards the more compact structures. This effect may also promote compact structures in partially folded proteins. Time-resolved dynamic non-radiative excitation energy transfer (tr-RET) is suitable for detection of either subtle or major changes in distributions of intramolecular distances in protein molecules in solutions. Two experiments were performed which demonstrated the applicability of tr-RET for detection of the effect of macrosolutes on the conformational ensembles of flexible states of protein molecules. The distribution of distances between residues 203 and 169 in the CORE domain of E. coli adenylate kinase (AK) in the denatured state was determined in the presence of high concentrations of dextran 40. A significant shift of the mean of the distribution was observed without reduction of its width. This was interpreted as a shift to compact structure without change of the degree of disorder of the chain. In a second experiment the distribution of the distance between residues 55 and 169 in AK, which spans the cleft between the CORE and the AMPbind domains, was monitored. No clear effect of high concentrations of dextran 40 was found. These experiments show the strength of the application of tr-RET in investigation of changes in the sub-states of flexible conformations of globular protein. Networks of pairs of labeled sites can be prepared and tr-RET experiments can be performed in order to search for the segments of the protein molecules, which respond to the presence of inert macromolecules in their environment.

Adenylate Kinase↗
PubMed1996

Persistence of multispecies host-parasitoid interactions in spatially distributed models with local dispersal.

Recent theoretical studies have shown that dispersal between neighbouring local populations can promote the persistence of interacting metapopulations, even when the local dynamics are unstable and the environment is uniform. This persistence is associated with striking and self-organized spatial patterns in the densities of the local populations. Here we extend previous work on spatially distributed host-parasitoid interactions to wider questions of community structure, by considering various three-species systems: two parasitoid species attacking a common host species; two host species attacked by a single parasitoid species; or a host-parasitoid-hyperparasitoid interaction. In each of these cases, multispecies coexistence of the total populations can occur, even though the local population dynamics are unstable. Furthermore, co-existence tends to be accompanied by some degree of persistent spatial segregation of the competing species, despite the completely uniform environment. At its most extreme, this results in one species being confined to small, relatively static, "islands" within the habitat, giving the appearance of isolated pockets of favourable habitat. That dynamics can impose and maintain such "self-organizing" spatial segregation of competing species, has interesting implications for understanding the local abundance of natural populations.

Animals↗
PubMed1987

Baroreflex-linked variations of catecholamine metabolism in the caudal ventrolateral medulla: an in vivo electrochemical study.

In vivo electrochemical recordings of the metabolism of catecholamines were obtained in the caudal ventrolateral medulla in anesthetized rats submitted to various experimental changes in systemic arterial pressure. Hypertension induced with phenylephrine and reversal of hypovolemia decreased the catechol metabolic activity. In contrast, controlled or hypovolemic hypotension, induced respectively with sodium nitroprusside or blood withdrawal (30% of blood volume), reversibly elicited the opposite pattern. This was suppressed by deafferentation. The changes in catechol metabolic activity in response to hypovolemia were accompanied by similar trends of variations of plasma vasopressin levels. By contrast with the increased catechol metabolic activity secondary to hypotension induced by either prazosin, sodium nitroprusside or hypovolemia, clonidine elicited a decrease in catechol metabolic activity. These data show a dynamic and specific involvement of the metabolism of catecholamines themselves promoted by changes in systemic arterial pressure. This pattern of functioning of catechol metabolism in the caudal ventrolateral medulla appears to be negatively related to systemic arterial pressure changes, a finding which does not fit with the proposed vasodepressor role of the A1-group.

Animals↗
PubMed2006

Challenges of developing the complex socio-technical system: realising the present, acknowledging the past, and envisaging the future of vessel traffic services.

This paper raises the question of how to guide the development of an emerging complex socio-technical system. The empirical basis for the discussion is a study of Vessel Traffic Services (VTS). We analysed the current state and the history of the service in Finland in four studies and identified several development needs. The results showed that there are differences between the outcome, practices and conceptions of the core task across different experts in the VTS centres, which can be explained by the current state of the constituents and the history of the activity system. Qualitatively different development phases characterised either by a top-down standardisation or bottom-up construction process were recognised. A combination of these processes was suggested for the future development strategy of the VTS. This could allow both continuous development within VTS and recognition of the need for a new system. A promising way to achieve continuous development is by creating reflective practices supported for instance with annual simulator exercises aimed at procedure development. We conclude that solving the current problems and promoting the development of the complex system call for a dynamic, open vision of the target future of the system, in which the pressures from the social, political and technological environments are taken into account. The results of ergonomics studies can help in self-reflecting, envisaging and developing supportive methods for the system but the persons within the system create the will to develop and find their way towards the development horizon.

Accident Prevention↗
PubMed2006

Sculpting the nervous system: glial control of neuronal development.

Glial cells are not passive spectators during nervous system assembly, rather they are active participants that exert significant control over neuronal development. Well-established roles for glia in shaping the developing nervous system include providing trophic support to neurons, modulating axon pathfinding, and driving nerve fasciculation. Exciting recent studies have revealed additional ways in which glial cells also modulate neurodevelopment. Glial cells regulate the number of neurons at early developmental stages by dynamically influencing neural precursor divisions, and at later stages by promoting neuronal cell death through engulfment. Glia also participate in the fine sculpting of neuronal connections by pruning excess axonal projections, shaping dendritic spines, and secreting multiple factors that promote synapse formation and functional maturation. These recent insights provide further compelling evidence that glial cells, through their diverse cellular actions, are essential contributors to the construction of a functionally mature nervous system.

Animals↗
PubMed2006

In vitro evaluation of herpes simplex virus type 1 thymidine kinase reporter system in dynamic studies of transcriptional gene regulation.

The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression model in vitro. The dynamic transcriptional events mediating a series of doxycycline (Dox) inductions were monitored by HSV1-TK or by the firefly luciferase reporter gene using HSV1-TK enzyme activity assay and luciferase assay, respectively. The results of dynamic gene expression studies showed that the luciferase gene is an optimal reporter gene for monitoring short-timescale, dynamic transcriptional events mediating a series of Dox inductions, whereas the HSV1-tk is not optimal to achieve this purpose. Furthermore, the enzyme half-life of HSV1-TK in NG4TL4 cells is about 35 h after cycloheximide-induced protein inhibition. On the other hand, the results of an efflux assay of [(131)I] FIAU and [(3)H] GCV revealed that the molecular probe phosphorylated by HSV1-TK can be trapped long term within HSV1-TK stably transformed cells. Therefore, a long half-life radionuclide is not suitable for dynamic gene expression studies. Based on these results, we suggest that the HSV1-TK reporter system is not optimal for monitoring short-timescale dynamic processes such as kinetic gene expression controlled by inducible promoters or a less stable protein with a more rapid turnover due to the limitations of the half-life of the HSV1-TK enzyme and the cellular retention time of their phosphorylated molecular probes.

Arabinofuranosyluracil↗
PubMed2005

Pediatric adherence: perspectives of mothers of children with HIV.

This study approached pediatric adherence practices from the perspective of mothers of children with HIV in the USA. The study aimed to articulate what is involved in the daily life experience of giving or supervising a child's HIV medication (i.e., adherence practices) in order to clarify, in more dynamic terms than is often found in adherence research, what promotes or impedes adherence. A team-based qualitative analytic approach was used to analyze the narrative responses of 71 maternal caregivers of children with HIV to interview questions regarding the activities and stresses of caring for a child with HIV. Four themes of dealing with medication on a daily basis that impacted mothers' adherence practices emerged from the analysis: (1) Mothers' attitudes and feelings related to adherence practices. (2) The impact of the medications on adherence practices. (3) Interactions of mothers and children related to adherence practices. (4) Developmental issues and responsibility for medication adherence. These themes, taken together, demonstrate the contextual and longitudinal factors that impact adherence and illustrate the complexity of influences on adherence practices. We found that adherence practices were impacted in a positive way by mothers' commitment to adherence, and in a negative way by feelings of stigma and guilt, by the effects of bereavement on children and by children adopting their mothers' attitudes about medications. The interactive process of giving medication was shaped by children's behavior, mothers' developmental expectations for children, and, for mothers with HIV, their adherence for themselves. We found that pediatric adherence often came at a cost to the caregiving mother's well-being.

Adolescent↗
PubMed2006

Heptachlor epoxide induces a non-capacitative type of Ca2+ entry and immediate early gene expression in mouse hepatoma cells.

The effects of the organochlorine (OC) liver tumor promoter heptachlor epoxide (HE) and a related non-tumor promoting OC, delta-hexachlorocyclohexane (delta-HCH), on the dynamics of intracellular calcium (Ca2+) were investigated in mouse 1c1c7 hepatoma cells. HE induced a non-capacitative, Ca2+ entry-like phenomenon, which was transient and concentration-dependent with 10 and 50 microM HE. The plasma membrane Ca2+ channel blocker SKF-96365 antagonized this HE-induced Ca2+ entry. delta-HCH failed to induce Ca2+ entry, rather it antagonized the HE-induced Ca2+ entry. Both HE and delta-HCH induced Ca2+ release from endoplasmic reticulum (ER) at treatment concentrations as low as 10 microM; at 50 microM, the former induced 5x as much Ca2+ release as the latter. The HE-induced Ca2+ release from the ER was antagonized using the IP3 receptor/channel blocker xestospongin C, suggesting that HE induces ER Ca2+ release through the IP3 receptor/channel pore. These results show that the effect of HE on cellular Ca2+ mimics that of mitogens such as epidermal and hepatocyte growth factors. They also provide insight into the similarities and differences between tumorigenic and non-tumorigenic OCs, in terms of the mechanisms and the extent of the [Ca2+]i increased by these agents.

Animals↗
PubMed2003

Mother's mitochondria and optimal offspring sex ratio.

In certain cases, predicted by evolutionary theory of sex-allocation and confirmed by empirical evidence, animals adaptively change their progeny sex-ratio according to individual circumstances. Here we argue that a similar response of offspring sex-ratio must exist in relation to genetic variation of mothers' mitochondria, as a consequence of maternal inheritance of these organelles and of their influence on fitness resulting from their crucial role in metabolism. In fact, a mathematical analysis of evolutionary dynamics of sex-allocation mutants demonstrates that natural selection promotes an evolutionarily stable allocation policy where mothers with defective mitochondria generate only sons, while those with optimal mitochondria have female biased progenies.

Animals↗
PubMedDate not supplied

Fat of the land.

Explore the source record for details and available documents.

Aged↗
PubMed1991

Second generation immune networks.

Network approaches have had little impact on immunology because they have addressed the wrong questions. They have concentrated on the regulation of clonal immune responses rather than on the supraclonal properties of the immune system that emerge from its network organization, such as natural tolerance and memory. Theoretical advances, observations in unimmunized mice and humans, and the success of novel therapeutics in autoimmune diseases have recently promoted a new burst of research on the structure, temporal dynamics and metadynamical plasticity of immune networks.

Animals↗
PubMed2003

Prevention of type 2 diabetes in young people: a theoretical perspective.

Type 2 diabetes in youth is an increasing public health concern, especially in certain minority populations. The current paper consists of four sections. First, we establish the significance of the problem by presenting an overview of epidemiological and physiological evidence. Second, we discuss behavioral issues relevant to the prevention of type 2 diabetes in youth. Third, a qualitative review of existing prevention interventions specific to type 2 diabetes in youth is presented. Results suggest that modest improvements in social cognitive, dietary, and exercise outcomes are possible with diabetes intervention studies, although beneficial changes are difficult to sustain over the long term. Although theoretical frameworks are not always explicit, most studies have utilized elements of the social cognitive theory. Less attention has been paid to sociocultural and community organization variables. Finally, the paper discusses issues of risk definition and intervention sustainability, and presents a comprehensive, theoretically diverse model for the prevention of type 2 diabetes in youth. In summary, we suggest that theories of the natural history and pathophysiology of type 2 diabetes are important to identify modifiable risk factors, while theories of behavioral change are essential to modify the risk factors identified. The combination of sound physiological and behavioral theories should form the basis of prevention intervention design. In addition, an ecologic approach that takes into consideration the dynamic interactions of personal, social, and environmental factors would best promote the long-term adoption of healthful behaviors in a supportive, meaningful, and personally enjoyable context.

Adolescent↗
PubMed2004

Genetic alterations of the NRP/B gene are associated with human brain tumors.

Nearly all brain tumors develop following the progressive accumulation of genetic alterations of oncogenes and tumor suppressor genes (such as p53 and retinoblastoma protein). Furthermore, aberrations in the nuclear matrix often contribute to genomic instabilities and the development of cancer. We have previously shown that nuclear-restricted protein/brain (NRP/B), a member of the BTB/Kelch repeat family, is a nuclear matrix protein normally expressed in neurons but not in astrocytes, and that it is an early and specific marker of neurons during the development of the central nervous system. Here, we show aberrant expression of NRP/B in human brain tissues. NRP/B is expressed in the cytoplasm of human brain tumor cells (glioblastoma, GBM) arising from astrocytes. NRP/B mutations (13 mutations in the Kelch domains, two in the intervening sequence (IVS) domain and two in the BTB domain) were detected in brain tumor cell lines (A-172, CCF-STTG1, SK-N-SH and U87-MG) and in primary human malignant GBM tissues (eight samples). More importantly, we found that NRP/B mutants, but not wild-type (wt) NRP/B, increased the activation of ERK and consequently promoted cell proliferation, attenuated caspase activation and suppressed the cellular apoptosis induced by the stressful stimulus cisplatin (10 microM). These events were observed to occur via a p53-mediated pathway. In addition, while wt NRP/B was associated with actin, mutations in the Kelch domains of NRP/B led to its reduced binding affinity to actin. Thus, alterations and gene mutations within the NRP/B gene may contribute to brain tumorigenesis by promoting cell proliferation, suppressing apoptosis and by affecting nuclear cytoskeleton dynamics.

Amino Acid Motifs↗
PubMed1997

FIS modulates growth phase-dependent topological transitions of DNA in Escherichia coli.

The Escherichia coli DNA-binding protein FIS serves as a DNA architectural factor in two unrelated enzymatic reactions, the site-specific inversion of DNA and transcriptional activation of stable RNA promoters. In both these processes, FIS facilitates the assembly and dynamic transitions of two structurally distinct nucleoprotein complexes. We have proposed previously that, in these systems, FIS stabilizes writhed DNA microloops by binding at multiple helically phased sites in DNA. However, FIS also binds and bends DNA at many non-specific sites and, at its maximum levels in the early exponential phase, FIS could potentially occupy a considerable part of the E. coli chromosome. Here, we show that fis affects growth phase-specific alterations in the supercoiling level of DNA. Expression of fis accelerates the accumulation of moderately supercoiled plasmids in stationary phase, which are stabilized by FIS after nutritional shift-up. In accordance with such a function, FIS modulates the relaxing and supercoiling activities of topoisomerases in vitro in a way that keeps DNA in a moderately supercoiled state. Our results suggest that the primary role of FIS is to modulate chromosomal dynamics during bacterial growth.

Carrier Proteins↗
PubMed2001

Regulation of global acetylation in mitosis through loss of histone acetyltransferases and deacetylases from chromatin.

Histone acetylation, a reversible modification of the core histones, is widely accepted to be involved in remodeling chromatin organization for genetic reprogramming. Histone acetylation is a dynamic process that is regulated by two classes of enzymes, the histone acetyltransferases (HATs) and histone deacetylases (HDACs). Although promoter-specific acetylation and deacetylation has received most of the recent attention, it is superimposed upon a broader acting and dynamic acetylation that profoundly affects many nuclear processes. In this study, we monitored this broader histone acetylation as cells enter and exit mitosis. In contrast to the hypothesis that HATs and HDACs remain bound to mitotic chromosomes to provide an epigenetic imprint for postmitotic reactivation of the genome, we observed that HATs and HDACs are spatially reorganized and displaced from condensing chromosomes as cells progress through mitosis. During mitosis, HATs and HDACs are unable to acetylate or deacetylate chromatin in situ despite remaining fully catalytically active when isolated from mitotic cells and assayed in vitro. Our results demonstrate that HATs and HDACs do not stably bind to the genome to function as an epigenetic mechanism of selective postmitotic gene activation. Our results, however, do support a role for spatial organization of these enzymes within the cell nucleus and their relationship to euchromatin and heterochromatin postmitotically in the reactivation of the genome.

Acetylation↗
PubMed2003

Reproductive uncertainty and the relative competitiveness of simultaneous hermaphroditism versus dioecy.

Hermaphroditism is typically associated with a sedentary existence, whereas dioecy is associated with mobility. This pattern is reflected within flowering plants, as dioecious species commonly possess traits that promote high dispersal. We investigated these associations with three population dynamics models (an individual-based simulation and two mathematical models, one deterministic and the other stochastic) that allowed us to examine competition for space between a hermaphroditic and dioecious species from different perspectives. The competing species are identical in every way but their sexual system. Separation of the sexes increases the variances of pollen import and seed dispersal for the dioecious species. These variances propagate through subsequent reproductive processes and ultimately reduce mean recruitment as a result of nonlinear averaging (Jensen's inequality). A dioecious species could overcome this disadvantage simply by producing more gametes than hermaphrodites; however, in line with the association with mobility, selection on dioecious species should also favor traits that reduce reproductive uncertainty, such as extensive dispersal.

Biological Evolution↗