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Mechanistic Hypotheses (mechanistic + hypothesis)
Selected AbstractsMechanistic hypotheses for nonsynaptic epileptiform activity induction and its transition from the interictal to ictal state,Computational simulationEPILEPSIA, Issue 11 2008Antônio-Carlos G. De Almeida Summary Purpose:, The aim of this work is to study, by means of computational simulations, the induction and sustaining of nonsynaptic epileptiform activity. Methods:, The computational model consists of a network of cellular bodies of neurons and glial cells connected to a three-dimensional (3D) network of juxtaposed extracellular compartments. The extracellular electrodiffusion calculation was used to simulate the extracellular potential. Each cellular body was represented in terms of the transmembrane ionic transports (Na+/K+ pumps, ionic channels, and cotransport mechanisms), the intercellular electrodiffusion through gap-junctions, and the neuronal interaction by electric field and the variation of cellular volume. Results:, The computational model allows simulating the nonsynaptic epileptiform activity and the extracellular potential captured the main feature of the experimental measurements. The simulations of the concomitant ionic fluxes and concentrations can be used to propose the basic mechanisms involved in the induction and sustaining of the activities. Discussion:, The simulations suggest: The bursting induction is mediated by the Cl, Nernst potential overcoming the transmembrane potential in response to the extracellular [K+] increase. The burst onset is characterized by a critical point defined by the instant when the Na+ influx through its permeable ionic channels overcomes the Na+/K+ pump electrogenic current. The burst finalization is defined by another critical point, when the electrogenic current of the Na+/K+ pump overcomes its influx through the channels. [source] Abundance , occupancy relationships in macrofauna on exposed sandy beaches: patterns and mechanismsECOGRAPHY, Issue 5 2004Matthew T. Frost We studied the relationship between abundance and extent of occupancy of 158 species of macrofauna inhabiting 66 sandy beaches around the coast of Great Britain. We also used these data to test the predictions of two hypotheses proposed to explain positive abundance-occupancy relationships. We found a strong positive relationship between abundance and extent of occupancy; this pattern was apparent in taxonomic subsets of organisms which have contrasting reproductive and dispersal traits such as planktotrophic/lecithotrophic development in the plankton vs brood development under parental care. Moreover, the abundance-occupancy relationships in these taxonomic subsets had statistically indistinguishable slopes, and elevation. We propose that this lends support to the notion that differences in population structure such as the tendency to form metapopulations may not be primary determinants of the abundance-occupancy pattern in these taxa as proposed by the rescue/metapopulation hypothesis. To test the predictions of the niche-breadth hypothesis we derived values describing the range of sediment grain-sizes exploited by members of two taxonomic subgroups: amphipods and bivalves. We found a weak, statistically non-significant relationship between this niche-breadth measure and occupancy in bivalves which have been shown to respond to grain-size in previous studies, however this was negated after correction for possible artefacts of sampling effort. All other relationships between abundance or occupancy and grain-size range were non-significant. The consistency of the demonstrated abundance-occupancy relationship with those demonstrated in other studies of primarily terrestrial fauna indicates some shared mechanistic explanation, but our data fail to provide support for the two mechanistic hypotheses investigated. [source] Integrating physiological, ecological and evolutionary change: a Price equation approachECOLOGY LETTERS, Issue 8 2009Sinéad Collins Abstract We use a general quantitative framework , the Price equation , to partition phenotypic responses to environmental change into separate physiological, evolutionary and ecological components. We demonstrate how these responses, which potentially occur over different timescales and are usually studied in isolation, can be combined in an additive way; and we discuss the main advantages of doing this. We illustrate our approach using two worked examples, concerning the emergence of toxin resistance within microbial communities, and the estimation of carbon uptake by marine phytoplankton in high-CO2 environments. We find that this approach allows us to exclude particular mechanistic hypotheses with regard to community-level transformations, and to identify specific instances where appropriate data are lacking. Thus Price's equation provides not only a powerful conceptual aid, but also a means for testing hypotheses and for directing empirical research programmes. [source] Use of mechanistic data in IARC evaluationsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2008Vincent James Cogliano Abstract Consideration of mechanistic data has the potential to improve the analysis of both epidemiologic studies and cancer bioassays. IARC has a classification system in which mechanistic data can play a pivotal role. Since 1991, IARC has allowed an agent to be classified as carcinogenic to humans (Group 1) when there is less than sufficient evidence in humans but there is sufficient evidence in experimental animals and "strong evidence in exposed humans that the agent acts through a relevant mechanism of carcinogenicity." Mechanistic evidence can also substitute for conventional cancer bioassays when there is less than sufficient evidence in experimental animals, just as mechanistic evidence can substitute for conventional epidemiologic studies when there is less than sufficient evidence in humans. The IARC Monographs have used mechanistic data to raise or lower a classification that would be otherwise based on epidemiologic studies and cancer bioassays only. Recently, the IARC Monographs have evaluated several agents where mechanistic data were pivotal to the overall evaluation: benzo[a]pyrene, carbon black and other poorly soluble particles, ingested nitrates and nitrites, and microcystin-LR. In evaluating mechanistic data, it is important to consider alternative mechanistic hypotheses, because an agent may induce tumors through multiple mechanisms. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] Habitat structure mediates predation risk for sedentary prey: experimental tests of alternative hypothesesJOURNAL OF ANIMAL ECOLOGY, Issue 3 2009Anna D. Chalfoun Summary 1Predation is an important and ubiquitous selective force that can shape habitat preferences of prey species, but tests of alternative mechanistic hypotheses of habitat influences on predation risk are lacking. 2We studied predation risk at nest sites of a passerine bird and tested two hypotheses based on theories of predator foraging behaviour. The total-foliage hypothesis predicts that predation will decline in areas of greater overall vegetation density by impeding cues for detection by predators. The potential-prey-site hypothesis predicts that predation decreases where predators must search more unoccupied potential nest sites. 3Both observational data and results from a habitat manipulation provided clear support for the potential-prey-site hypothesis and rejection of the total-foliage hypothesis. Birds chose nest patches containing both greater total foliage and potential nest site density (which were correlated in their abundance) than at random sites, yet only potential nest site density significantly influenced nest predation risk. 4Our results therefore provided a clear and rare example of adaptive nest site selection that would have been missed had structural complexity or total vegetation density been considered alone. 5Our results also demonstrated that interactions between predator foraging success and habitat structure can be more complex than simple impedance or occlusion by vegetation. [source] Hot topics in aging research: protein translation, 2009AGING CELL, Issue 6 2009Brian K. Kennedy Summary In the last few years, links between regulation of mRNA translation and aging have been firmly established in invertebrate model organisms. This year, a possible relationship between mRNA translation and aging in mammals has been established with the report that rapamycin increases lifespan in mice. Other significant findings have connected translation control with other known longevity pathways and provided fodder for mechanistic hypotheses. Here, we summarize advances in this emerging field and raise questions for future studies. [source] Decomposition dynamics in mixed-species leaf litterOIKOS, Issue 2 2004Tracy B. Gartner Literature on plant leaf litter decomposition is substantial, but only in recent years have potential interactions among leaves of different species during decomposition been examined. We review emerging research on patterns of mass loss, changes in nutrient concentration, and decomposer abundance and activity when leaves of different species are decaying in mixtures. Approximately 30 papers have been published that directly examine decomposition in leaf mixtures as well as in all component species decaying alone. From these litter-mix experiments, it is clear that decomposition patterns are not always predictable from single-species dynamics. (Characteristics of decomposition in litter-mixes that deviate from responses predicted from decomposition of single-species litters alone are designated "non-additive"; "additive" responses in mixes are predictable from component species decaying alone.) Non-additive patterns of mass loss were observed in 67% of tested mixtures; mass loss is often (though not always) increased when litters of different species are mixed. Observed mass loss in some mixtures is as much as 65% more extensive than expected from decomposition of single-species litter, but more often mass loss in mixtures exceeds expected decay by 20% or less. Nutrient transfer among leaves of different species is striking, with 76% of the mixtures showing non-additive dynamics of nutrient concentrations. Non-additive patterns in the abundance and activity of decomposers were observed in 55% and 65% of leaf mixes, respectively. We discuss some methodological details that likely contribute to conflicting results among mixed-litter studies to date. Enough information is available to begin formulating mechanistic hypotheses to explain patterns in litter-mix experiments. Emerging patterns in the mixed-litter decomposition literature have implications for relationships between biodiversity and ecosystem function (in this case, the function being decomposition), and for potential mechanisms through which invasive plant species could alter carbon and nutrient dynamics in ecosystems. [source] 3142: Radiation-induced lens opacities: towards a new strategy to address the low dose risk research with the European network DoReMiACTA OPHTHALMOLOGICA, Issue 2010P GOURMELON In 2010, a Network of Excellence called DoReMi was launched by the EURATOM FP7 programme. DoReMi will act during the next six years as an operational tool for the development of a research platform devoted to low dose risk research in Europe. The research activities of DoReMi are implemented within three work packages: WP5, WP6, and WP7, which are respectively concerned with the shape of the dose effect relationship, individual radiation sensitivity and non-cancer effects. The overarching objective of WP7 is to implement a long-term, integrated approach involving several disciplines, namely, epidemiology, radiobiology and toxicology, for the purpose of risk evaluation for radiation-induced non-cancer effects. One of the operational objectives of the DoReMi WP7 consists of undertaking feasibility studies addressing the issues of vascular effects, lens opacities and cognitive effects. The presentation to be given will provide the assembly with (i) information about the European low dose risk research strategy; (ii) latest knowledge about the epidemiological evidence of radiation-induced lens opacities; (iii) information about the feasibility study of lens opacities to be launched in a group of interventional cardiologists (iv) most promising mechanistic hypotheses for the development of radiation-induced lens opacities recognizing that while posterior subcapsular cataracts are characteristic of an exposure to ionizing radiation, several sets of data suggest that the broader category of posterior cortical cataracts may also be regarded as radiation-associated. Eventually the presentation will discuss the issue of a threshold for the development of radiation-induced lens opacities and list the scientific questions raised by the radiation protection community to the vision and eye research community. [source] [(NHC)AuI]-Catalyzed Formation of Conjugated Enones and Enals: An Experimental and Computational StudyCHEMISTRY - A EUROPEAN JOURNAL, Issue 22 2007Nicolas Marion Abstract The [(NHC)AuI]-catalyzed (NHC = N-heterocyclic carbene) formation of ,,,-unsaturated carbonyl compounds (enones and enals) from propargylic acetates is described. The reactions occur at 60,°C in 8,h in the presence of an equimolar mixture of [(NHC)AuCl] and AgSbF6 and produce conjugated enones and enals in high yields. Optimization studies revealed that the reaction is sensitive to the solvent, the NHC, and, to a lesser extent, to the silver salt employed, leading to the use of [(ItBu)AuCl]/AgSbF6 in THF as an efficient catalytic system. This transformation proved to have a broad scope, enabling the stereoselective formation of (E)-enones and -enals with great structural diversity. The effect of substitution at the propargylic and acetylenic positions has been investigated, as well as the effect of aryl substitution on the formation of cinnamyl ketones. The presence or absence of water in the reaction mixture was found to be crucial. From the same phenylpropargyl acetates, anhydrous conditions led to the formation of indene compounds via a tandem [3,3] sigmatropic rearrangement/intramolecular hydroarylation process, whereas simply adding water to the reaction mixture produced enone derivatives cleanly. Several mechanistic hypotheses, including the hydrolysis of an allenol ester intermediate and SN2, addition of water, were examined to gain an insight into this transformation. Mechanistic investigations and computational studies support [(NHC)AuOH], produced in situ from [(NHC)AuSbF6] and H2O, instead of cationic [(NHC)AuSbF6] as the catalytically active species. Based on DFT calculations performed at the B3LYP level of theory, a full catalytic cycle featuring an unprecedented transfer of the OH moiety bound to the gold center to the CC bond leading to the formation of a gold,allenolate is proposed. Es descriu la reacció de formació de compostos de carbonil ,,, -insaturats (enones i enals) a partir d,acetats propargílics catalitzada per [(NHC)AuI] (NHC=carbè N-heterocíclic). Les reaccions tenen lloc a 60,°C en 8,h en presència d,una mescla equimolar de [(NHC)AuCl] i AgSbF6 i produeix rendiments alts d,enones i enals conjugats. Estudis d,optimització van mostrar que la reacció era sensible al solvent, el NHC, i, en menor grau, a la natura de la sal de plata emprada; això va portar a escollir [(ItBu)AuCl]/AgSbF6 en THF com a sistema catalític eficient. La transformació va mostrar posseir un ampli espectre, i es va aconseguir la formació estereoselectiva d,(E)-enones i -enals amb gran diversitat estructural. La influència de la substitució en les posicions propargílica i acetilènica va ser investigada, així com la substitució d,aril per donar lloc a la formació de cinamilcetones. La presència o absència d,aigua en el medi de reacció es va mostrar com a crucial. A partir dels mateixos fenilpropargilacetats, condicions anhidres van portar a la formació de compostos indènics mitjançant una reacció tàndem de reorganització sigmatròpica [3,3] i hidroarilació intramolecular, mentre que l,addició d,aigua a la reacció portava de manera neta a derivats del tipus enona. Diverses hipòtesis mecanístiques, entre elles la hidròlisi d,un intermedi del tipus al.lenol ester i l,addició SN2, d,aigua, han estat examinades per millorar la comprensió del procés. Les dades mecanístiques i els estudis computacionals suggereixen que l,espècie catalítica activa és [(NHC)AuOH], produït in situ a partir de [(NHC)AuSbF6] i H2O, i no el complex catiònic [(NHC)AuSbF6]. A partir d,estudis DFT realitzats al nivell B3LYP, es proposa un cicle catalític complet, que inclou un nou tipus d,etapa consistent en la transferència d,un grup OH des de l,or cap a l,enllaç CC per produir un complex or-al.lenolat. [source] From pre-cells to Eukarya , a tale of two lipidsMOLECULAR MICROBIOLOGY, Issue 1 2003G. Wächtershäuser Summary A mechanistic hypothesis for the origin of the three domains of life is proposed. A population of evolving pre-cells is suggested to have had a membrane of a racemate of chiral lipids that continuously underwent spontaneous symmetry breaking by spatial phase segregation into two enantiomerically enriched membrane domains. By frequent pre-cell fusions and fissions these membrane domains became partitioned between two pre-cell subpopulations having predominantly one lipid enantiomer or the other. The origin of the Bacteria and Archaea is explained by divergence of first a population of proto-bacteria and later a population of proto-archaea from the evolving pre-cells, each by the emergence of an enantio-selective lipid biosynthesis within the corresponding pre-cell subtype. The origin of the Eukarya is explained by symbiosis between a population of Bacteria and a subpopulation of pre-cells with a predominance of the bacteria-type lipid enantiomers. [source] From Solution-Phase to Solid-Phase Enyne Metathesis: Crossover in the Relative Performance of Two Commonly Used Ruthenium Pre-CatalystsCHEMISTRY - A EUROPEAN JOURNAL, Issue 17 2005Dominic E. A. Brittain Dr. Abstract A crossover in the ability of two distinct ruthenium-based metathesis pre-catalysts to effect the synthesis of dialkenylboronic esters in solution and on the solid-phase was observed. Specifically, while the Grubbs 2nd generation pre-catalyst 3 affords a greater degree of conversion to product than the Hoveyda,Grubbs pre-catalyst 2 in a solution-phase enyne-metathesis reaction, this trend is reversed in the solid-phase variant. Systematic investigation showed this trend to be general, regardless of variations in the homoallylic alcohol and alkynylboronic ester components of the reaction, as well as in the type of solid support employed. Experiments to determine a mechanistic hypothesis for this trend highlighted the significance of the ruthenium remaining bound to the substrate after metathetic rearrangement and found the presence of phosphine ligand to be detrimental to the success of the solid-phase reaction. Therefore, these results suggest an expanded role for phosphine-free pre-catalysts, such as 2, in challenging solid-phase metathesis reactions. [source] | |||||||||||||