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Principal Mechanism (principal + mechanism)
Selected AbstractsLIFE-HISTORY DIFFERENTIATION AND THE MAINTENANCE OF MONOECY AND DIOECY IN SAGITTARIA LATIFOLIA (ALISMATACEAE)EVOLUTION, Issue 9 2003Marcel E. Dorken Abstract The existence of monoecious and dioecious populations within plant species is rare. This limits opportunities to investigate the ecological mechanisms responsible for the evolution and maintenance of these contrasting sexual systems. In Sagittaria latifolia, an aquatic flowering plant, monoecious and dioecious populations exist in close geographic proximity but occupy distinct wetland habitats differing in the relative importance of disturbance and competition, respectively. Life-history theory predicts contrasting evolutionary responses to these environmental conditions. We propose that the maintenance of monoecy and dioecy in S. latifolia is governed by ecological selection of divergent life-history strategies in contrasting habitats. Here we evaluate this hypothesis by comparing components of growth and reproduction between monoecious and dioecious populations under four conditions: natural populations, a uniform glasshouse environment, a common garden in which monoecious and dioecious populations and their F1 progeny were compared, and a transplant experiment using shaded and unshaded plots in a freshwater marsh. Plants from dioecious populations were larger in size and produced heavier corms in comparison with monoecious populations. Monoecious populations flowered earlier and produced more flowers, clonal ramets, and corms than dioecious populations. The life-history differences between the sexual systems were shown to have a quantitative genetic basis, with F1 progeny generally exhibiting intermediate trait values. Survival was highest for each sexual system in field plots that most closely resembled the habitats in which monoecious (unshaded) and dioecious (shaded) populations grow. These results demonstrate that monoecious and dioecious populations exhibit contrasting patterns of investment in traits involved with growth and reproduction. Selection for divergent life histories between monoecious and dioecious populations of S. latifolia appears to be the principal mechanism maintaining the integrity of the two sexual systems in areas of geographic overlap. [source] Altering DNA base excision repair: Use of nuclear and mitochondrial-targeted N -methylpurine DNA glycosylase to sensitize astroglia to chemotherapeutic agents,GLIA, Issue 14 2007Jason F. Harrison Abstract Primary astrocyte cultures were used to investigate the modulation of DNA repair as a tool for sensitizing astrocytes to genotoxic agents. Base excision repair (BER) is the principal mechanism by which mammalian cells repair alkylation damage to DNA and involves the processing of relatively nontoxic DNA adducts through a series of cytotoxic intermediates during the course of restoring normal DNA integrity. An adenoviral expression system was employed to target high levels of the BER pathway initiator, N -methylpurine glycosylase (MPG), to either the mitochondria or nucleus of primary astrocytes to test the hypothesis that an alteration in BER results in increased alkylation sensitivity. Increasing MPG activity significantly increased BER kinetics in both the mitochondria and nuclei. Although modulating MPG activity in mitochondria appeared to have little effect on alkylation sensitivity, increased nuclear MPG activity resulted in cell death in astrocyte cultures treated with methylnitrosourea (MNU). Caspase-3 cleavage was not detected, thus indicating that these alkylation sensitive astrocytes do not undergo a typical programmed cell death in response to MNU. Astrocytes were found to express relatively high levels of antiapoptotic Bcl-2 and Bcl-XL and very low levels of proapoptotic Bad and Bid suggesting that the mitochondrial pathway of apoptosis may be blocked making astrocytes less vulnerable to proapoptotic stimuli compared with other cell types. Consequently, this unique characteristic of astrocytes may be responsible, in part, for resistance of astrocytomas to chemotherapeutic agents. © 2007 Wiley-Liss, Inc. [source] The impact of Investors in People: a case study of a hospital trustHUMAN RESOURCE MANAGEMENT JOURNAL, Issue 3 2002Irena Grugulis This article reports on case study research conducted in a hospital trust and explores the impact that the Investors in People award had on employees. Investors in People is widely seen as the principal mechanism for increasing workforce skills within a voluntarist system as well as supporting ,good' employment policies. Yet in this case study, as elsewhere, most of the ,soft' HR initiatives had existed prior to accreditation and the internal marketing of corporate value statements was met with both amnesia and cynicism. More worrying, training activity was focused on ,business need', which was defined in the narrowest sense, with the result that some employees had fewer opportunities for individual development. Motivation and commitment levels were high, staff were enthusiastic about their work and many actively engaged in training and development. But this owed little to Investors in People, and its impact here raises questions about its influence on skill levels more broadly. [source] Block of HERG-Carried K+ Currents by the New Repolarization Delaying Agent H 345/52JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2003Gregory J. Amos M.D. Ph.D. Introduction: The aim of this study was to analyze the block of HERG-carried membrane currents caused by H 345/52, a new antiarrhythmic compound with low proarrhythmic activity, in transfected mouse fibroblasts. Methods and Results: Using the whole-cell configuration of the voltage patch clamp technique, it was demonstrated that H 345/52 concentration-dependently blocked HERG-carried currents with an IC50 of 230 nM. H 345/52 preferentially bound to the open channel with unusually rapid kinetics and was trapped by channel closure. Voltage-independent behavior of H 345/52 was observed during both square-pulse and action potential clamp protocols. In contrast, the Class III agents dofetilide (10 nM) and almokalant (250 nM) demonstrated significant membrane potential-dependent effects during square-pulse clamp protocols. When using action potential clamp protocols, voltage dependence was seen with dofetilide but not with almokalant. Mathematical simulations of human ventricular action potentials predicted that the different voltage-dependent behaviors would not produce marked variations in action potential duration prolongation patterns. Conclusion: We propose that block of IKr is the principal mechanism by which H 345/52 delays repolarization in human myocardium. The voltage independence of HERG/IKr block is unlikely to underlie the low proarrhythmic potential, and ancillary effects on other membrane currents must be considered. (J Cardiovasc Electrophysiol, Vol. 14, pp. 651-658, June 2003) [source] Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonographyLASERS IN SURGERY AND MEDICINE, Issue 3 2006DECVDI, Stefanie Ohlerth Dr. Med.Vet. Abstract Background and Objectives One principal mechanism of photodynamic therapy (PDT) in tumors is destruction of tumor-associated vasculature. In the present study, the vascular effects of PDT in tumors were investigated with power Doppler ultrasonography. Materials and Methods Seven cutaneous squamous cell carcinomas in cats were treated. Tumors were examined via power Doppler ultrasonography before, 5 minutes, 1 hour, and 24 hours after PDT. Images were digitized for computer-aided assessment of vascularity and blood volume. Results Mean baseline tumor vascularity and blood volume were moderate. During PDT, a significant decrease in vascularity and blood volume was noted. Lowest values were found 24 hours after PDT. Conclusions Power Doppler ultrasonography represents a non-invasive modality to successfully monitor the vascular effects and thus, treatment efficacy, of PDT. Lasers Surg. Med. 38:229,234, 2006. © 2006 Wiley-Liss, Inc. [source] Photodynamic therapy in dermatology: state-of-the-artPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2010Philipp Babilas Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo-aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non-oncologic indications. [source] Empowerment and State Education: Rights of Choice and ParticipationTHE MODERN LAW REVIEW, Issue 6 2005Neville Harris Two separate discourses surround the involvement of parents in their children's education in schools. One is concerned with what is often referred to as ,parent power,' based on the conferment on parents of rights to a degree of choice and participation in respect of their children's education, a feature of legislative changes to the governance of state education that started with the Education Act 1980 and which, in part, rests on consumerist and liberal rights based notions. The other focuses on the home-school partnership ideal in which parents and schools have obligations to support each other in realising children's potential. Labour and Conservative 2005 general election campaigns included proposals to ,empower' parents. But social rights such as those in education, which are important to notions of citizenship, tend to be weak. This article concludes that over the past 25 years little power has been ceded to parents, individually or collectively, and that, in the case of rights of choice at least, any further empowerment seems unrealistic. Moreover, the principal mechanism of parental involvement, particularly since 1997, has been the enforcement of parental responsibility, a form of ,technology of citizenship'. The extent to which children hold participation and choice rights is also considered. [source] Population genetic structure and conservation of Asian elephants (Elephas maximus) across IndiaANIMAL CONSERVATION, Issue 4 2005T. N. C. Vidya This study examines the population genetic structure of Asian elephants (Elephas maximus) across India, which harbours over half the world's population of this endangered species. Mitochondrial DNA control region sequences and allele frequencies at six nuclear DNA microsatellite markers obtained from the dung of free-ranging elephants reveal low mtDNA and typical microsatellite diversity. Both known divergent clades of mtDNA haplotypes in the Asian elephant are present in India, with southern and central India exhibiting exclusively the , clade of Fernando et al. (2000), northern India exhibiting exclusively the , clade and northeastern India exhibiting both, but predominantly the , clade. A nested clade analysis revealed isolation by distance as the principal mechanism responsible for the observed haplotype distributions within the , and , clades. Analyses of molecular variance and pairwise population FST tests based on both mitochondrial and microsatellite DNA suggest that northern-northeastern India, central India, Nilgiris (in southern India) and Anamalai-Periyar (in southern India) are four demographically autonomous population units and should be managed separately. In addition, evidence for female philopatry, male-mediated gene flow and two possible historical biogeographical barriers is described. [source] Characterization of alternatively spliced transcripts encoding heat shock transcription factor in cultured cells of the cabbage armyworm, Mamestra brassicaeARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2010Shoji Sonoda Abstract A gene encoding heat shock transcription factor (HSF) was cloned and sequenced from cultured cells of the cabbage armyworm, Mamestra brassicae. The cDNA potentially encoded a 699-aa protein, with a calculated molecular weight of 77.8,kDa. Deduced amino acid identities to HSFs from Aedes aegypti and Drosophila melanogaster were 36 and 34%, respectively. Analysis of the genomic DNA revealed eight exons and three optional exons: a, b, and c. Exon a contained a premature in-frame stop codon that would generate a truncated protein. When the cells were exposed to high temperature or cadmium, no particular alternative transcripts showed significant up- or down-regulated expression relative to the total amount of the transcripts. These results suggest that alternative splicing may not be a principal mechanism for regulation of M. brassicae HSF gene expression in response to heat shock and cadmium. © 2009 Wiley Periodicals, Inc. [source] The tail end of hummingbird evolution: parallel flight system development in living and ancient birdsBIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 3 2009ROBERT BLEIWEISS Evolutionary innovations are central to debates about biological uniformitarianism because their very novelty implies a distinct evolutionary dynamic. Traditional scenarios for innovations in the development of avian powered flight exemplify the kinds of distinctions considered to occur at different times during the history of innovations. Thus, the progressive change of the wing stroke mechanism early in its evolution is considered to have imposed strong functional and historical constraints on tail shape diversity, whereas attainment of the modern flight stroke mechanism is considered to have liberated the tail to radiate into a wide variety of other functions and forms. Detailed analyses of living hummingbirds revealed that these highly aerial birds actually expressed many parallel functional constraints and historically progressive patterns observed earlier in avian history: (1) more basal lineages had relatively weak wing muscles (patagial muscles and tendons, TPB), convex to square tails, and more linear flight employed in nonterritorial foraging; (2) more derived lineages had a stronger TPB, forked tails, accentuated growth of tail fork, and more manoeuvrable and agile flight employed in territorial foraging; and (3) the most derived lineage had the strongest TPB, greatly reduced tails, and mainly bee-like flight. These associations make functional sense because convex tails increase stability and efficiency in linear flight, concave tails augment lift for turning flight in territorial defence, and tails become aerodynamically disadvantageous if the wings provide sufficient lift. Derived hummingbird lineages also demonstrated the same expansion of tail shape and taxonomic diversity associated with perfection of the modern wing stroke mechanism earlier in avian history. Thus, living hummingbirds are a microcosm of overall avian flight evolution. Other living avian (,aerial courser') and extinct reptilian (Pterosaur) clades with extraordinary flight abilities provide evidence for similar patterns, suggesting a broadly defined uniformitarianism (early constraint followed by later radiation) at the limits of the flight performance envelope throughout vertebrate history. Correlated evolution of TPB and tail form suggests that natural selection on an integrated flight system was the principal mechanism fostering the avian patterns, although strengthening of wing muscles in derived lineages may have facilitated expansion of caudal morphological diversity through a balance between natural and sexual selection on males. These findings suggest that wing muscles, locomotor integration, and phylogenetic patterns are essential for understanding function and adaptation of tails in living as well as ancient birds. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 97, 467,493. [source] Reference Values Describing the Normal Mitral Valve and the Position of the Papillary MusclesECHOCARDIOGRAPHY, Issue 7 2007Petrus Nordblom M.Sc. In patients with functional mitral regurgitation (MR), the principal mechanisms are insufficient coaptation due to dilatation of the mitral annulus (MA), global ventricular dysfunction with tethering of leaflets, or restricted leaflet motion with incorrect apposition due to regional ventricular dysfunction and displacement of the papillary muscles (PMs). These different entities often coexist and for this reason, knowledge of the normal reference values describing the shape and size of the MA and the position of the PMs is essential. In the present study, we describe the MA dimensions and the position of the PMs in a group of normal individuals (n = 38, 60% women, age [mean ± SD] 51 ± 9 years and BSA 1.83 ± 0.16 m2) investigated with transthoracic echocardiography. The anteroposterior dimension (AP) of the ellipse-shaped MA was measured in a parasternal long axis, while the distance from the posteromedial (PoM) to the anterolateral (AL) commissure was measured in a parasternal short axis (CC). The annular area was calculated assuming elliptic geometry. The MA shape was described by the ratios AP/CC and AP/length of the anterior leaflet. The PMs' position was described by the following distances: (a) from the MA to the tip of the PoM and AL, PMs measured in a modified two-chamber view where both PMs could be identified, (b) the interpapillary distance, and (c) the tethering distance from the tip of the PM to the contralateral MA. These data on the normal mitral valve morphology should provide useful information when assessing the underlying mechanism of functional MR. [source] Zoledronate has an antitumor effect and induces actin rearrangement in dexamethasone-resistant myeloma cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2007Masayuki Koizumi Abstract New strategies are needed to overcome the resistance of multiple myeloma (MM) to dexamethasone (Dex). Several recent in vitro studies demonstrated the antitumor effect of nitrogen-containing amino-bisphosphonates (N-BPs) in various tumor cell lines. Inhibition of the prenylation of small G proteins is assumed to be one of the principal mechanisms by which N-BPs exert their effects. There have been few reports on N-BP treatment of MM cells that are resistant to Dex. Additionally, it is not known how small G proteins are altered in N-BP-treated MM cells. In this study, we evaluated the effect of the most potent N-BP, zoledronate (ZOL), on a Dex-resistant human MM cell subline (Dex-R) that we established from the well-documented RPMI8226 cell line. ZOL reduced the viability and induced apoptosis of Dex-R cells. Some of the ZOL-treated RPMI8226 cells and ZOL-treated Dex-R cells were elongated; however, elongated cells were not seen among the Dex-treated RPMI8226 cells. Furthermore, we found that portions of the small G proteins, Rho and Rap1A, were unprenylated in the ZOL-treated MM cells. Geranylgeraniol reduced the above-mentioned ZOL-induced effects. These findings suggest that ZOL may be beneficial for the treatment of Dex-resistant MM by suppressing the processing of RhoA and Rap1A. [source] The evolutionary ecology of senescenceFUNCTIONAL ECOLOGY, Issue 3 2008P. Monaghan Summary 1Research on senescence has largely focused on its underlying causes, and is concentrated on humans and relatively few model organisms in laboratory conditions. To understand the evolutionary ecology of senescence, research on a broader taxonomic range is needed, incorporating field, and, where possible, longitudinal studies. 2Senescence is generally considered to involve progressive deterioration in performance, and it is important to distinguish this from other age-related phenotypic changes. We outline and discuss the main explanations of why selection has not eliminated senescence, and summarise the principal mechanisms thought to be involved. 3The main focus of research on senescence is on age-related changes in mortality risk. However, evolutionary biologists focus on fitness, of which survival is only one component. To understand the selective pressures shaping senescence patterns, more attention needs to be devoted to age-related changes in fecundity. 4Both genetic and environmental factors influence the rate of senescence. However, a much clearer distinction needs to be drawn between life span and senescence rate, and between factors that alter the overall risk of death, and factors that alter the rate of senescence. This is particularly important when considering the potential reversibility and plasticity of senescence, and environmental effects, such as circumstances early in life. 5There is a need to reconcile the different approaches to studying senescence, and to integrate theories to explain the evolution of senescence with other evolutionary theories such as sexual and kin selection. [source] Can the evolutionary-rates hypothesis explain species-energy relationships?FUNCTIONAL ECOLOGY, Issue 6 2005K. L. EVANS Summary 1There is growing consensus that much of the marked broad-scale spatial variation in species richness is associated with variation in environmental energy availability, but at least nine principal mechanisms have been proposed that may explain these patterns. 2The evolutionary-rates hypothesis suggests that high environmental energy availability elevates rates of molecular evolution, promoting faster speciation, so that more species occur in high-energy areas because more evolve there. Direct tests of this hypothesis are rare and their conclusions inconsistent. Here we focus on assessing the support for its underlying assumptions. 3First, the evolutionary-rates hypothesis assumes that high energy levels promote mutation. There is certainly evidence that high levels of ultraviolet radiation increase mutation rates. High temperatures may also reduce generation times and elevate metabolic rates, which may promote mutation. On balance, data support a link between rates of metabolism and mutation, but a link between the latter and generation time is more equivocal and is particularly unlikely in plants. 4Second, the evolutionary-rates hypothesis assumes that mutation rates limit speciation rates. This may be true if all else was equal, but correlations between mutation and speciation are probably very noisy as many other factors may influence rates both of sympatric and allopatric speciation, including the occurrence of physical isolation barriers, the magnitude of selection and population size. 5Third, the evolutionary-rates hypothesis assumes that there is a strong correlation between current and historical energy levels. Factors such as tectonic drift may weaken such relationships, but are likely to have had negligible effects over the time period during which the majority of extant species evolved. 6Fourth, the evolutionary-rates hypothesis assumes that changes in species ranges following speciation do not sufficiently weaken the correlation between the rate of speciation in an area and species richness. The ranges of many species appear to alter dramatically following speciation, and this may markedly reduce the strength of the relationship, but to what extent is unclear. 7In sum, the degree to which the evolutionary-rates hypothesis can explain spatial variation in species richness remains surprisingly uncertain. We suggest directions for further research. [source] Paternal transmission of genetic damage: findings in animals and humansINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2000Martin H. Brinkworth The concept that mutations can be induced in the male germ-line and result in adverse effects in the offspring has achieved only limited acceptance despite considerable theoretical appeal. This is partly because fetal malformations are generally perceived to be induced solely as a result of maternally mediated events during gestation and partly because the low incidence of the end-points concerned make experimental approaches costly and time-consuming. Nonetheless, a substantial body of work relating to the hypothesis has accumulated in the last 20 years, which has never been reviewed in its entirety. A consideration of the available evidence indicates that preconceptional paternal exposure to mutagens (particularly radiation, cyclophosphamide and ethylnitrosourea) can indeed, under certain conditions, have adverse effects on offspring. The results suggest two principal mechanisms by which such effects may be induced: the induction of germ-line genomic instability or the suppression of germ cell apoptosis. [source] Bioceramic Bone Graft Substitutes: Influence of Porosity and ChemistryINTERNATIONAL JOURNAL OF APPLIED CERAMIC TECHNOLOGY, Issue 3 2005Karin A. Hing Bioceramics have been considered for use as synthetic bone graft substitutes (BGSs) for over 30 years, throughout which there have been two primary areas of research: (i) optimization of the physical pore structure and (ii) formulation of an appropriate bioceramic chemistry. While it is well recognized that both the rate of integration and the final volume of regenerated bone are primarily dependent on the macroporosity, there still seems to be some dispute regarding the optimum "type" of porosity. The rate and quality of bone integration have, in turn, been related to a dependence on pore size, porosity volume fraction, and interconnection size and interconnection density, both as a function of structural permeability and mechano-transduction. Moreover, the role of strut microstructure and pore geometry have been considered with respect to their influence on entrapment and recruitment of growth factors (GFs) in addition to its influence on scaffold mechanics. Deconvoluting the relative affects of these parameters is complicated by the use of both resorbable and nonresorbable bioactive bioceramics, which are believed to mediate bioactivity in the osseous environment through two principal mechanisms: (i) directly through dissolution and release of ionic products in vivo, elevating local concentrations of soluble species that interact directly with local cells or influence cell behavior by their effect on local pH, (ii) indirectly through the influence that surface chemistry will have on protein adsorption, GF entrapment, and subsequent cell attachment and function. This article aims to review some of the recent developments in bioceramic BGSs, with a view to understanding how the various physiochemical parameters may be optimized to promote bone healing. [source] Biotic homogenization: a new research agenda for conservation biogeographyJOURNAL OF BIOGEOGRAPHY, Issue 12 2006Julian D. Olden Abstract Aim, Biotic homogenization describes the process by which species invasions and extinctions increase the genetic, taxonomic or functional similarity of two or more biotas over a specified time interval. The study of biotic homogenization is a young and rapidly emerging research area in the budding field of conservation biogeography, and this paper aims to synthesize our current knowledge of this process and advocate a more systematic approach to its investigation. Methods, Based on a comprehensive examination of the primary literature this paper reviews the process of biotic homogenization, including its definition, quantification, underlying ecological mechanisms, environmental drivers, the empirical evidence for different taxonomic groups, and the potential ecological and evolutionary implications. Important gaps in our knowledge are then identified, and areas of new research that show the greatest promise for advancing our current thinking on biotic homogenization are highlighted. Results, Current knowledge of the patterns, mechanisms and implications of biotic homogenization is highly variable across taxonomic groups, but in general is incomplete. Quantitative estimates are almost exclusively limited to freshwater fishes and plants in the United States, and the principal mechanisms and drivers of homogenization remain elusive. To date research has focused on taxonomic homogenization, and genetic and functional homogenization has received inadequate attention. Trends over the past decade, however, suggest that biotic homogenization is emerging as a topic of greater research interest. Main conclusions, My investigation revealed a number of important knowledge gaps and priority research needs in the science of biotic homogenization. Future studies should examine the homogenization process for different community properties (species occurrence and abundance) at multiple spatial and temporal scales, with careful attention paid to the various biological mechanisms (invasions vs. extinctions) and environmental drivers (environmental alteration vs. biotic interactions) involved. Perhaps most importantly, this research should recognize that there are multiple possible outcomes resulting from the accumulation of species invasions and extinctions, including biotic differentiation whereby genetic, taxonomic or functional similarity of biotas decreases over time. [source] Human Subjects Protections in Biomedical Enhancement Research: Assessing Risk and Benefit and Obtaining Informed ConsentTHE JOURNAL OF LAW, MEDICINE & ETHICS, Issue 3 2008Maxwell J. Mehlman The protection of human subjects in biomedical research relies on two principal mechanisms: assessing and comparing the risks and potential benefits of proposed research, and obtaining potential subjects' informed consent. While these have been discussed extensively in the literature, no attention has been paid to whether the processes should be different when the objective of an experimental biomedical intervention is to improve individual appearance, performance, or capability ("enhancement research") rather than to prevent, cure, or mitigate disease ("health-oriented research"). This essay examines this question in order to ensure that subjects in biomedical enhancement research receive adequate protection. [source] | |||||||||||||||||||