bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships between exercise capacity and front hoof longitudinal balance in horses
Authors: Tacchio G , Davies HMS , Morgante M , Bernardini D
Published: May 2005

To the authors' knowledge, the effect of hoof balance alteration on exercise capacity or performance has not been investigated. With the aim of evaluating the relationships between longitudinal front hoof balance and exercise capacity (lactate vs. speed relationship, run time and stride characteristics), two experiments were undertaken. In the first test the horses, left unshod, performed an incremental speed test in which parameters chosen to evaluate exercise capacity were related to hoof longitudinal balance. In the second part of the study the same group of horses had the length of the toe altered (decreased and increased) with the application of shoes, while the angle of the foot and the height of the foot from the ground remained the same. The relative change in exercise capacity due to the alteration of longitudinal balance was observed. In the unshod experiment, lactate level at the speed of 10 ms-1(5.0±2.0 mmoll-1) was significantly associated with the angles DC° (angle described by the dorsal cortex with respect to the ground; 50.0±3.2°) and PC° (angle described by the palmar cortex with respect to the ground; 29.6 ± 2.9°), while run time (14.07 ± 1.44 min) was associated with breakover indices (Breakover index1 0.33±0.03; Breakover index2 0.30 ± 0.04 – all values mean ± standard deviation (SD)) (breakover indices were created to express the distance between the point of the toe and the point of the third phalanx relative to the length of the palmar cortex or relative to the distance between the point of the third phalanx and the centre of rotation of the distal interphalangeal joint). These associations have to be judged cautiously because the influence of hoof balance on exercise capacity could be biased by other physiological factors and because hoof balance parameters themselves could reflect the conformation of other anatomical structures far from the phalanges. The selective alteration of front hoof balance in the second part of the study produced a significant difference in blood lactate level only at 6 ms-1(mean ± SD: La6?m?s-10.32 ± 0.39 mmoll-1), with this benefit in terms of lactate level being associated with an increase in stride length (mean ± SD: ΔSL6ms-10.01 ± 0.05 m; ΔSL10ms-10.112 ± 0.218 m). In conclusion, while higher exercise capacity seemed to be associated with lower DC°, PC° and breakover indices, decreasing the toe length without altering the foot angle was beneficial only in terms of lactate level at the speed of 6 ms-1for horses with DC° greater than 45°; this benefit was accompanied by a slight lengthening of the stride at both 6 and 10 ms-1.
Hoof landing velocity is related to track surface properties in trotting horses
Authors: Burn Jeremy F , Usmar Steven J
Published: May 2005

The resistance of a track surface to deformation is known to be positively related to the magnitude of foot impact experienced during locomotion. Although passive mechanics suggests that this might be entirely due to the action of the track surface material decelerating the foot, it is also possible that the dynamics of locomotion are altered in a way that changes the landing velocity of the foot. The observed relationship between track properties and foot impact would then be due to a combination of the direct effect of the surface material and altered foot kinematics at impact. In this study we measured hoof landing velocity, stance time and limb landing angle in horses trotting over surfaces that differed significantly in their deformability. In comparison with a surface that underwent negligible deformation during stance phase, a surface that deformed 25 mm led to significantly increased stance time, significantly greater leg landing angle and significantly greater hoof landing velocity. Although the increased hoof landing velocity would act to counteract the increased shock absorption on the softer surface, we suggest that this effect is relatively small.
Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response
Authors: Ercolini Anne M. , Ladle Brian H. , Manning Elizabeth A. , Pfannenstiel Lukas W. , Armstrong Todd D. , Machiels Jean-Pascal H. , Bieler Joan G. , Emens Leisha A. , Reilly R. Todd , Jaffee Elizabeth M.
Published: May 2005

A major barrier to successful antitumor vaccination is tolerance of high-avidity T cells specific to tumor antigens. In keeping with this notion, HER-2/neu (neu)-targeted vaccines, which raise strong CD8+ T cell responses to a dominant peptide (RNEU420-429) in WT FVB/N mice and protect them from a neu-expressing tumor challenge, fail to do so in MMTV-neu (neu-N) transgenic mice. However, treatment of neu-N mice with vaccine and cyclophosphamide-containing chemotherapy resulted in tumor protection in a proportion of mice. This effect was specifically abrogated by the transfer of neu-N–derived CD4+CD25+ T cells. RNEU420-429-specific CD8+ T cells were identified only in neu-N mice given vaccine and cyclophosphamide chemotherapy which rejected tumor challenge. Tetramer-binding studies demonstrated that cyclophosphamide pretreatment allowed the activation of high-avidity RNEU420-429-specific CD8+ T cells comparable to those generated from vaccinated FVB/N mice. Cyclophosphamide seemed to inhibit regulatory T (T reg) cells by selectively depleting the cycling population of CD4+CD25+ T cells in neu-N mice. These findings demonstrate that neu-N mice possess latent pools of high-avidity neu-specific CD8+ T cells that can be recruited to produce an effective antitumor response if T reg cells are blocked or removed by using approaches such as administration of cyclophosphamide before vaccination.
Role of SHPS-1 in the Regulation of Insulin-like Growth Factor I–stimulated Shc and Mitogen-activated Protein Kinase Activation in Vascular Smooth Muscle Cells
Authors: Ling Yan , Maile Laura A. , Lieskovska Jaroslava , Badley-Clarke Jane , Clemmons David R.
Published: May 2005

Insulin-like growth factor I (IGF-I) stimulates smooth muscle cell (SMC) proliferation, and the mitogen-activated protein kinase (MAPK) pathway plays an important role in mediating IGF-I–induced mitogenic signaling. Our prior studies have shown that recruitment of Src homology 2 domain tyrosine phosphatase (SHP-2) to the membrane scaffolding protein Src homology 2 domain–containing protein tyrosine phosphatase substrate-1 (SHPS-1) is required for IGF-I–dependent MAPK activation. The current studies were undertaken to define the upstream signaling components that are required for IGF-I–stimulated MAPK activation and the role of SHPS-1 in regulating this process. The results show that IGF-I–induced Shc phosphorylation and its subsequent binding to Grb2 is required for sustained phosphorylation of MAPK and increased cell proliferation in SMCs. Furthermore, for Shc to be phosphorylated in response to IGF-I requires that Shc must associate with SHPS-1 and this association is mediated in part by SHP-2. Preincubation of cells with a peptide that contains a phospho-tyrosine binding motif sequence derived from SHPS-1 inhibited IGF-I–stimulated SHP-2 transfer to SHPS-1, the association of Shc with SHPS-1, and IGF-I–dependent Shc phosphorylation. Expression of an SHPS-1 mutant that did not bind to Shc or SHP-2 resulted in decreased Shc and MAPK phosphorylation in response to IGF-I. In addition, SMCs expressing a mutant form of the β3 subunit of the αVβ3, which results in impairment of SHP-2 transfer to SHPS-1, also showed attenuated IGF-I–dependent Shc and MAPK phosphorylation. Further analysis showed that Shc and SHP-2 can be coimmunoprecipitated after IGF-I stimulation. A cell-permeable peptide that contained a polyproline sequence from Shc selectively inhibited Shc/SHP-2 association and impaired Shc but not SHP-2 binding to SHPS-1. Exposure to this peptide also inhibited IGF-I–stimulated Shc and MAPK phosphorylation. Cells expressing a mutant form of Shc with the four prolines substituted with alanines showed no Shc/SHPS-1 association in response to IGF-I. We conclude that SHPS-1 functions as an anchor protein that recruits both Shc and SHP-2 and that their recruitment is necessary for IGF-I–dependent Shc phosphorylation, which is required for an optimal mitogenic response in SMCs.
Specific Features of Neuronal Size and Shape Are Regulated by Tropomyosin Isoforms
Authors: Schevzov Galina , Bryce Nicole S. , Almonte-Baldonado Rowena , Joya Josephine , Lin Jim J.-C. , Hardeman Edna , Weinberger Ron , Gunning Peter
Published: May 2005

Spatially distinct populations of microfilaments, characterized by different tropomyosin (Tm) isoforms, are present within a neuron. To investigate the impact of altered tropomyosin isoform expression on neuronal morphogenesis, embryonic cortical neurons from transgenic mice expressing the isoforms Tm3 and Tm5NM1, under the control of the β-actin promoter, were cultured in vitro. Exogenously expressed Tm isoforms sorted to different subcellular compartments with Tm5NM1 enriched in filopodia and growth cones, whereas the Tm3 was more broadly localized. The Tm5NM1 neurons displayed significantly enlarged growth cones accompanied by an increase in the number of dendrites and axonal branching. In contrast, Tm3 neurons displayed inhibition of neurite outgrowth. Recruitment of Tm5a and myosin IIB was observed in the peripheral region of a significant number of Tm5NM1 growth cones. We propose that enrichment of myosin IIB increases filament stability, leading to the enlarged growth cones. Our observations support a role for different tropomyosin isoforms in regulating interactions with myosin and thereby regulating morphology in specific intracellular compartments.
Qualitative Leverage and the Epistemology of Expert Opinion
Authors: Gordon Sanford C. , Smith Alastair
Published: May 2005

We discuss the motivation for integrating qualitative information in statistical models of complex, partially observable causal mechanisms and suggest ways to minimize the dangers posed by Braumoeller and Kirpichevsky. We stress the importance of linking our statistical estimators to underlying theories of the data generating process, qualitative or otherwise.
HU‐α binds to the putative double‐stranded DNA mimic HI1450 from Haemophilus influenzae
Authors: Parsons Lisa M. , Liu Fang , Orban John
Published: May 2005

Recently, the solution structure of the hypothetical protein HI1450 from Haemophilus influenzae was solved as part of a structure‐based effort to understand function. The distribution of its many negatively charged residues and weak structure and sequence homology to uracil DNA glycosylase inhibitor (Ugi) suggested that HI1450 may act as a double‐stranded DNA (dsDNA) mimic. We present supporting evidence here and show that HI1450 interacts with the dsDNA‐binding protein HU‐α. The interaction between HI1450 and HU‐α from H. influenzae is characterized using calorimetry and NMR spectroscopy. HU‐α binds to HI1450 with a Kd of 3.0 ± 0.2 μM, which is similar in affinity to its interaction with dsDNA. Chemical shift perturbation data indicate that the β1‐strand of HI1450 and neighboring regions are most directly involved in interactions with HU‐α. These results show that HI1450 and its structural homolog, Ugi, use similar parts of their structures to recognize DNA‐binding proteins.
Calcium‐ and magnesium‐dependent interactions between calcium‐ and integrin‐binding protein and the integrin αIIb cytoplasmic domain
Authors: Yamniuk Aaron P. , Vogel Hans J.
Published: May 2005

Calcium‐ and integrin‐binding protein (CIB) is a small EF‐hand calcium‐binding protein that is involved in hemostasis through its interaction with the αIIb cytoplasmic domain of integrinαIIbβ3. We have previously demonstrated that CIB lacks structural stability in the absence of divalent metal ions but that it acquires a well‐folded conformation upon addition of Ca2+ or Mg2+. Here, we have used fluorescence spectroscopy, NMR spectroscopy, and isothermal titration calorimetry to demonstrate that both Ca2+‐bound CIB (Ca2+‐CIB) and the Mg2+‐bound protein (Mg2+‐CIB) bind with high affinity and through a similar mechanism to αIIb cytoplasmic domain peptides, but that metal‐free CIB (apo‐CIB) binds in a different manner. The interactions are thermodynamically distinct for Ca2+‐CIB and Mg2+‐CIB, but involve hydrophobic interactions in each case. Since the Mg2+ concentration inside the cell is sufficient to saturate CIB at all times, our results imply that CIB would be capable of binding to the αIIb cytoplasmic domain independent of an intracellular Ca2+ stimulus in vivo. This raises the question of whether CIB can act as a Ca2+ sensor in αIIbβ3 signaling or if other regulatory mechanisms such as fibrinogen‐induced conformational changes in αIIbβ3, post‐translational modifications, or the binding of other accessory proteins mediate the interactions between CIB and αIIbβ3. Differences in NMR spectra do suggest, however, that Ca2+‐binding to the Mg2+‐ CIB‐αIIb complex induces subtle structural changes that could further modulate the activity of αIIbβ3.
Capsid structure and dynamics of a human rhinovirus probed by hydrogen exchange mass spectrometry
Authors: Wang Lintao , Smith David L.
Published: May 2005

Viral capsids are dynamic protein assemblies surrounding viral genomes. Despite the high‐resolution structures determined by X‐ray crystallography and cryo‐electron microscopy, their in‐solution structure and dynamics can be probed by hydrogen exchange. We report here using hydrogen exchange combined with protein enzymatic fragmentation and mass spectrometry to determine the capsid structure and dynamics of a human rhinovirus, HRV14. Capsid proteins (VP1–4) were labeled with deuterium by incubating intact virus in D2O buffer at neutral pH. The labeled proteins were digested by immobilized pepsin to give peptides analyzed by capillary reverse‐phase HPLC coupled with nano‐electrospray mass spectrometry. Deuterium levels incorporated at amide linkages in peptic fragments were measured for different exchange times from 12 sec to 30 h to assess the amide hydrogen exchange rates along each of the four protein backbones. Exchange results generally agree with the crystal structure of VP1–4,with extended, flexible terminal and surface‐loop regions in fast exchange and folded helical and sheet structures in slow exchange. In addition, three α‐helices, one from each of VP1–3, exhibited very slow exchange, indicating high stability of the protomeric interface. The β‐strands at VP3 N terminus also had very slow exchange, suggesting stable pentamer contacts. It was noted, however, that the interface around the fivefold axis had fast and intermediate exchange, indicating relatively more flexibility. Even faster exchange rates were found in the N terminus of VP1 and most segments of VP4, suggesting high flexibilities, which may correspond to their potential roles in virus uncoating.
Within‐ and between‐species patterns of allocation to pulp and seed in vertebrate dispersed plants
Authors: Edwards Will
Published: May 2005

Non‐uniform scaling of pulp and seed mass has been shown to alter dispersal probabilities in vertebrate dispersed species. Since dispersal in tropical forests is strongly linked to establishment success, processes determining allocation to pulp and seed are likely to impact on parental fitness, and therefore should be under the control of natural selection. In this study I examine size‐dependent dry mass allocation pattern to pulp and seed mass both among and within 20 fruit‐producing plant species of tropical rainforest in northeast Queensland, Australia. Reduced major axis analyses using mean values for each species showed significant isometry, indicating that at the community level, plant species that employ vertebrates as a means of seed dispersal tend to allocate an equivalent mean relative proportion of the overall dry weight investment in fruit to pulp. However, identical analyses conducted for each species separately revealed that relationships within individual species do not reflect the inter‐specific relationship. These results imply two influences on dry mass allocation to fruit components; the first (within‐species allometry) determines how fruits vary within each species. The second (between‐species allometry) operates in a similar manner across species to produce equal ratios of mean pulp and seed mass independent of within‐species allometries.
Ecological subsystems via graph theory: the role of strongly connected components
Authors: Allesina Stefano , Bodini Antonio , Bondavalli Cristina
Published: May 2005

In this paper we investigate ecological flow networks via graph theory in search of the real sequential chains through which energy passes from producers to consumers in complex food webs. We obtain such fundamental pathways by identifying strongly connected components (SCCs), subsystems that groups species that take part in cycling, and performing topological sorting on the acyclic graphs that are obtained. Topological sorting identifies preferential directions for energy to flow from sources to sinks, while recycling remains confined within each SCC. Resolving food web networks for SCC highlights the possibility that compartments can be found in ecosystems, but this does not seem a general rule. The four aquatic food webs described in detail show a rather clear subdivision between benthic and pelagic subcommunities, a result that is discussed in the light of other studies. Should further research confirm these results, new insight into the way ecosystems use energy will be provided, with implications on cycling, reciprocal dependency of variables and indirect effects.
The interaction of plant genotype and herbivory decelerate leaf litter decomposition and alter nutrient dynamics
Authors: Schweitzer Jennifer A. , Bailey Joseph K. , Hart Stephen C. , Wimp Gina M. , Chapman Samantha K. , Whitham Thomas G.
Published: May 2005

We examined how plant genetic variation and a common herbivore (the leaf‐galling aphid,Pemphigus betae) influenced leaf litter quality, decomposition, and nutrient dynamics in a dominant riparian tree (Populus spp.). Based on both observational studies and a herbivore exclusion experiment using trees of known genotype, we found four major patterns: 1) the quality of galled vs non‐galled or gall‐excluded litter significantly differed in the concentration of condensed tannins, lignin, nitrogen and phosphorus; 2) the difference in litter quality resulted in galled litter decomposing at rates 34 to 40% slower than non‐galled litter; 3) plant genotype and herbivory had similar effects on the magnitude of decomposition rate constants; and 4) plant genotype mediated the herbivore effects on leaf litter quality and decomposition, as there were genotype‐specific responses to herbivory independent of herbivore density. In contrast to other studies that have demonstrated accelerated ecosystem properties in response to arthropod herbivory, our findings argue that herbivore‐induced secondary compounds decelerated ecosystem properties though their “after‐life” effects on litter quality. Furthermore, these data are among the first to suggest that genotype‐specific responses to herbivores can have a major impact on decomposition and nutrient flux, which likely has important consequences for the spatial distribution of nutrients at the landscape level. Due to the magnitude of these effects, we contend that it is important to incorporate a genetic perspective into ecosystem studies.
Which traits promote persistence of feral GM crops? Part 1:implications of environmental stochasticity
Authors: Claessen David , Gilligan Christopher A. , Lutman Peter J. W. , Bosch Frank van den
Published: May 2005

Transgenes in plants affect life history traits including seed survival and germination. With stochastic matrix models we predict population‐level consequences of transgene induced life history changes. We assess systematically which changes in life history traits, resulting from genetic modification, may increase the risk of invasion and persistence of feral crops or increase fitness in case of introgression from arable fields into conspecific, feral populations. We apply our method to feral populations of oilseed rape. Like many annual weeds, oilseed rape depends critically on disturbance; in undisturbed habitats it is generally outcompeted by perennials. The associated inherent variability and unpredictability render deterministic models inappropriate. With a stochastic matrix model we study population growth rate, elasticities and quasi‐extinction times. Our results indicate that changes in survival in the seed bank impact population growth and persistence most. Less important are dormancy, fecundity and seedling survival. The predicted distribution of extinction times is highly skewed, with some patches persisting for decades.
Which traits promote persistence of feral GM crops? Part 2: implications of metapopulation structure
Authors: Claessen David , Gilligan Christopher A. , Van Den Bosch Frank
Published: May 2005

Transgenes may spread from crops into the environment via the establishment of feral populations, often initiated by seed spill from transport lorries or farm machinery. Locally, such populations are often subject to large environmental variability and usually do not persist longer than a few years. Because secondary feral populations may arise from seed dispersal to adjacent sites, the dynamics of such populations should be studied in a metapopulation context. We study a structured metapopulation model with local dispersal, mimicking a string of roadside subpopulations of a feral crop. Population growth is assumed to be subject to local disturbances, introducing spatially random environmental stochasticity. Our aim is to understand the role of dispersal and environmental variability in the dynamics of such ephemeral populations. We determine the effect of dispersal on the extinction boundary and on the distribution of persistence times, and investigate the influence of spatially correlated disturbances as opposed to spatially random disturbances. We find that, given spatially random disturbances, dispersal slows down the decline of the metapopulation and results in the occurrence of long‐lasting local populations which remain more or less static in space. We identify which life history traits, if changed by genetic modification, have the largest impact on the population growth rate and persistence times. For oilseed rape, these are seed bank survival and dormancy. Combining our findings with literature data on transgene‐induced life history changes, we predict that persistence is promoted by transgenes for oil‐modifications (high stearate or high laurate) and, possibly, for insect resistence (Bt). Transgenic tolerance to glufosinate herbicide is predicted to reduce persistence.
Indirect effects of deer herbivory on local nitrogen availability in a coastal dune ecosystem
Authors: McNeil Sean G. , Cushman J. Hall
Published: May 2005

Herbivores can have indirect effects on local nutrient availability if their direct effects on plants lead to changes in the amount or chemical composition of litter reaching the soil surface. Using two exclosure experiments, we evaluated this possibility for black‐tailed deer (Odocoileus hemionus columbianus) feeding on silver bush lupine (Lupinus chamissonis) in a coastal dune system in northern California. Our first experiment assessed the effects of deer herbivory on 360 lupines that were tracked from newly germinated seedlings in 1996 and 1997 until 2000, when most surviving individuals had reached reproductive age. Results from this experiment showed that browsing by deer significantly reduced growth rates and seed production of lupines and delayed the onset of reproductive maturity. Although deer had no effect on the density of litter accumulating underneath shrubs (g m−2), browsing significantly decreased C:N ratios of leaf tissue, due primarily to increased nitrogen content of leaves. Deer browsing also caused significantly increased net nitrogen mineralization rates in the soil under shrubs, although pools of ammonium and nitrate were uninfluenced. The second experiment examined 72 established bush lupines from 1997 to 2000, and showed that deer browsing significantly decreased seed production but had no effect on shrub growth. We also detected trends for browsed shrubs to have reduced pools of ammonium and nitrate underneath their canopies, although no such patterns emerged for nitrogen mineralization rates. Collectively, these data suggest that changes in litter quality, more so than litter quantity, contributed to the indirect effects of deer herbivory on local nitrogen dynamics. We hypothesize that deer browsing induced chemical changes in lupine plant tissue, which increased the nitrogen content of litter reaching the soil surface and subsequently increased rates of nitrogen mineralization.
Phenotypic plasticity in gender specific life‐history: effects of food availability and predation
Authors: Mikolajewski Dirk Johannes , Brodin Tomas , Johansson Frank , Joop Gerrit
Published: May 2005

If environmental conditions vary, plasticity in life‐history traits is predicted. A recent model indicates that males and females should differ in life‐history traits, because sexes differ in optimal attributes depending on species ecology. In this study we test the impact of two biotic factors in combination (presence/absence of predators and low/high food level) on gender specific life‐history traits in the damselfly Coenagrion puella (Odonata). Results show that predator presence and low food density decreased activity in both sexes. Additionally, individuals with less food grew more slowly, emerged later, remained smaller and had a higher mortality. At low food densities, however, and in contrast to former investigations, individuals from treatments with predator presence were the same size or larger than individuals without predators. Gender had a strong impact on larval activity and life‐history traits and sexes differed in development. Females were less active and took longer to complete development, but emerged at a larger size, weight and fat content. This study highlights the importance of gender specific approaches in life‐history research.
Density‐dependent reproductive output in relation to a drastically varying food supply: getting the density measure right
Authors: Lindström Åke , Enemar Anders , Andersson Göran , Proschwitz Ted von , Nyholm N. Erik I.
Published: May 2005

When a limiting resource (e.g. food) varies drastically between years, and population density is measured in the conventional way as individuals per area, demographic processes such as productivity and survival may erroneously be considered density‐independent. We tested the hypothesis that if the variation in a limiting resource is not taken into account in the density measure, this may lead to erroneous conclusions about the density‐dependence of demographic variables. We studied the food‐related variation in productivity of bramblings Fringilla montifringilla, an insectivorous passerine bird, using 19 years of standardised insect censusing, bird censusing and mist‐netting of birds in subalpine birch forest in Swedish Lapland. The yearly variation in our measure of brambling per capita productivity (numbers of juveniles per adult trapped) was explained to 30–40% by the larvae abundance of the moth Epirrita autumnata. Taking larvae density into account, no other environmental variable (inferred predation pressure, breeding phenology, and summer temperature) was significantly related to variation in reproductive output. There was no effect of brambling population density on per capita productivity, that is, when density was measured the conventional way, productivity seemed density‐independent. However, per capita productivity was significantly and negatively correlated to the food‐related population density (population density divided by larval density), supporting the hypothesis that not including a limiting resource into the density measure may indeed lead to erroneous conclusions about the density‐dependence of demographic variables.
Species richness, temporal variability and resistance of biomass production in a Mediterranean grassland
Authors: Caldeira M. C. , Hector A. , Loreau M. , Pereira J. S.
Published: May 2005

We studied the temporal variability and resistance to perturbation of the biomass production of grassland communities from an experimental diversity gradient (the Portuguese BIODEPTH project site). With increasing species richness relative temporal variability (CV) of plant populations increased but that of communities decreased, supporting the insurance hypothesis and related theory. Species‐rich communities were more productive than species‐poor communities in all three years although a natural climatic perturbation in the third year (frequent frost and low precipitation) caused an overall decrease in biomass production. Resistance to this perturbation was constant across the experimental species richness gradient in relative terms, supporting a similar response from the Swiss BIODEPTH experiment. The positive biomass response was generated by different combinations of the complementarity and selection effects in different years. Complementarity effects were positive across mixtures on average in all three years and positively related to diversity in one season. The complementarity effect declined following perturbation in line with total biomass but, counter to predictions, in relative terms overyielding was maintained in all years. Selection effects were positively related to diversity in one year and negative overall in the other two years. The response to perturbation varied among species and for the same species growing in monoculture and mixture, but following the frost communities were more strongly dominated by species with lower monoculture biomass and the selection effect was more negative. In total, our results support previous findings of a positive relationship between diversity and productivity and between diversity and the temporal stability of production, but of no effect of diversity on the resistance to perturbation. We demonstrate for the first time that the relative strength of overyielding remained constant during an exceptional natural environmental perturbation.
Direct experimental evidence for alternative stable states: a review
Authors: Schröder Arne , Persson Lennart , De Roos André M.
Published: May 2005

A large number of studies have presented empirical arguments for the existence of alternative stable states (ASS) in a wide range of ecological systems. However, most of these studies have used non‐manipulative, indirect methods, which findings remain open for alternative explanations. Here, we review the direct evidence for ASS resulting from manipulation experiments. We distinguish four conclusive experimental approaches which test for predictions made by the hysteresis effect: (1) discontinuity in the response to an environmental driving parameter, (2) lack of recovery potential after a perturbation, (3) divergence due to different initial conditions and (4) random divergence. Based on an extensive literature search we found 35 corresponding experiments. We assessed the ecological stability of the reported contrasting states using the minimum turnover of individuals in terms of life span and classified the studies according to 4 categories: (1) experimental system, (2) habitat type, (3) involved organisms and (4) theoretical framework. 13 experiments have directly demonstrated the existence of alternative stable states while 8 showed the absence of ASS in other cases. 14 experiments did not fulfil the requirements of a conclusive test, mostly because they applied a too short time scale. We found a bias towards laboratory experiments compared to field experiments in demonstrating bistability. There was no clear pattern of the distribution of ASS over categories. The absence of ASS in 38% of the tested systems indicates that ASS are just one possibility of how ecological systems can behave. The relevance of the concept of ASS for natural systems is discussed, in particular under consideration of the observed laboratory bias, perturbation frequency and variable environments. It is argued, that even for a permanently transient system, alternative attractors may still be of relevance.
Cellular automata and ecology
Authors: Rohde Klaus
Published: May 2005

A fascinating and potentially very fertile new approach for solving various scientific problems in mathematics, physics, cosmology, chemistry, biology, psychology and economics, to mention only the most important ones, is that pioneered by Stephan Wolfram. In the following, I give a brief outline of his “NKS” (new kind of science”) with emphasis on cellular automata; some of his conclusions concerning evolutionary biology; a comparison with other approaches; and an application of the method to some problems of ecology.

The principles of NKS (“new kind of science”) developed by Stephen Wolfram are discussed, with emphasis on cellular automata. Wolfram's conclusions concerning optimisation and the evolution of complexity in biological systems are outlined and compared with those from some other recent approaches. NKS is applied to some central problems of ecology, i.e. the possibility of establishing general ecological laws, the existence of vacant niches, the importance of interspecific competition and the causes of latitudinal gradients in species diversity.
The role of CD8+ T‐cell replicative senescence in human aging
Authors: Effros Rita B. , Dagarag Mirabelle , Spaulding Carolyn , Man Janice
Published: May 2005

Summary:  The strict limit in proliferative potential of normal human somatic cells – a process known as replicative senescence – is highly relevant to the immune system, because clonal expansion is fundamental to adaptive immunity. CD8+ T cells that undergo extensive rounds of antigen‐driven proliferation in cell culture invariably reach the end stage of replicative senescence, characterized by irreversible cell‐cycle arrest and a critically short telomere length. Cultures of senescent CD8+ T cells also show resistance to apoptosis, permanent loss of CD28 expression, altered cytokine profiles, reduced ability to respond to stress, and various functional changes. Cells with similar characteristics accumulate during normal aging as well as in younger persons infected with human immunodeficiency virus, suggesting that the process of replicative senescence is not an artifact of cell culture but is also occurring in vivo. Interestingly, in elderly persons, the presence of high proportions of CD8+ T cells with characteristics of replicative senescence is correlated with reduced antibody responses to vaccines as well as with osteoporotic fractures. CD8+CD28– T cells also accumulate in patients with certain types of cancer. The emerging picture is that senescent CD8+ T cells may modulate both immune and non‐immune functions, contributing not only to reduced anti‐viral immunity but also to diverse age‐related pathologies.
Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age‐associated microenvironmental changes
Authors: Stout Robert D. , Suttles Jill
Published: May 2005

Summary:  The macrophage lineage displays extreme functional and phenotypic heterogeneity, which appears to be because, in large part, of the ability of macrophages to functionally adapt to changes in their tissue microenvironment. This functional plasticity of macrophages plays a critical role in their ability to respond to tissue damage and/or infection and to contribute to clearance of damaged tissue and invading microorganisms, to recruitment of the adaptive immune system, and to resolution of the wound and of the immune response. Evidence has accumulated that environmental influences, such as stromal function and imbalances in hormones and cytokines, contribute significantly to the dysfunction of the adaptive immune system. The innate immune system also appears to be dysfunctional in aged animals and humans. In this review, the hypothesis is presented and discussed that the observed age‐associated ‘dysfunction’ of macrophages is the result of their functional adaptation to the age‐associated changes in tissue environments. The resultant loss of orchestration of the manifold functional capabilities of macrophages would undermine the efficacy of both the innate and adaptive immune systems. The macrophages appear to maintain functional plasticity during this dysregulation, making them a prime target of cytokine therapy that could enhance both innate and adaptive immune systems.
Non‐malignant clonal expansions of CD8+ memory T cells in aged individuals
Authors: Clambey Eric T. , Van Dyk Linda F. , Kappler John W. , Marrack Philippa
Published: May 2005

Summary:  CD8+ T cells provide a major line of defense against intracellular pathogens. Upon encounter with antigen, CD8+ T cells go through three distinct phases involving proliferation, contraction, and differentiation to become eventually long‐lived CD8+ memory T cells. CD8+ memory T cells provide long‐term protection against infection by intracellular pathogens. CD8+ memory T‐cell proliferation and survival are regulated by many factors, including cytokines, and CD8+ memory T cells are stably maintained over a period of months to years. In aged humans and mice, however, there are significant alterations to the CD8+ memory T‐cell compartment with frequent development of monoclonal expansions of CD8+ memory T cells in healthy individuals. Interestingly, CD8+ clonal expansions are not malignant and do not progress to lymphomas, suggesting that these cells must still be under certain constraints. In this review, we discuss our current understanding of factors that contribute to and regulate these CD8+ clonal expansions as well as the impact of CD8+ clonal expansions on immune function of the aged. In addition, we discuss similarities and differences between CD8+ clonal expansions observed in humans and mice, and we postulate that CD8+ clonal expansions represent a spectrum of biological outcomes ranging from antigen‐driven to antigen‐independent phenomena.
The aging of early B‐cell precursors
Authors: Allman David , Miller Juli P.
Published: May 2005

Summary:  B‐cell genesis in the bone marrow declines with advancing age. In this review, we discuss our current understanding of why B‐cell production rates decline with age with a special emphasis on why age‐related factors might target very early lymphoid precursors. We consider the impact of aging on cytokine responsiveness and how current models for lineage relationships for very early B‐ and T‐cell precursors might influence interpretations of experiments addressing age‐associated declines in B‐ and T‐cell differentiation. This discussion centers on the notion that aging affects events associated with the process by which hematopoietic stem cells are guided toward the B‐cell pathway. Finally, we present a model in which the age‐associated loss of early B‐cell precursors is linked to suboptimal function of key transcriptional regulators of very early B‐cell development.
B cells and aging: gauging the interplay of generative, selective, and homeostatic events
Authors: Cancro Michael P.
Published: May 2005

Summary:  Lymphocyte homeostasis encompasses a continuum of processes that together determine the production, turnover, composition, and representation of lymphocyte pools. These processes include commitment to lymphoid lineages, expansion of progenitor pools, successful transit through intermediate maturation stages, negative and positive selection based on receptor specificity, steady‐state maintenance of peripheral lymphocytes, and regulation of antigen‐driven activation. Understanding the impact of aging on lymphocyte homeostasis thus requires appreciation of not only the mechanisms responsible for generating and sustaining antigen‐reactive B and T cells but also how age‐related events can subvert these. Even under the influence of normally operating homeostatic mechanisms, lesions yielding perturbations outside of evolutionarily anticipated boundaries will yield aberrant lymphoid function and representation both upstream and downstream of the primary defect. Accordingly, determining the relative contribution of lineage‐intrinsic versus compensatory homoeostatic processes throughout the continuum of lymphoid system development, selection, and maintenance are critical first steps towards understanding age‐associated alterations in the immune system.
Expression of hurpin, a serine proteinase inhibitor, in normal and pathological skin: overexpression and redistribution in psoriasis and cutaneous carcinomas
Authors: Moussali Hayat , Bylaite Matilda , Welss Thomas , Abts Harry F. , Ruzicka Thomas , Walz Markus
Published: May 2005

Abstract:  Hurpin was identified by differential display analysis studying UV‐repressible genes in the keratinocyte cell line HaCaT. We have previously reported that hurpin mRNA is overexpressed in psoriatic skin compared to non‐lesional or normal skin; hurpin inhibits cathepsin L and that, after overexpression in keratinocytes, hurpin decreases UV‐induced apoptosis. To further study the expression of hurpin, we have isolated monoclonal antibodies against hurpin and analyzed its expression in normal and diseased skin by immunohistochemistry (IHC). In the epidermis of normal skin, we found hurpin to be mainly expressed in the stratum basale. In contrast, we found an enhanced expression of hurpin in the stratum spinosum and stratum granulosum in the majority of diseased skin samples. Within the dermis of normal and diseased skin, hurpin was detected in sebaceous and sweat glands, hair follicles, and endothelial cells of blood vessels. Hurpin was localized in the cytoplasm in normal and diseased skin. Additionally to IHC, we analyzed hurpin expression in selected skin diseases by semiquantitative reverse‐transcription polymerase chain reaction. We found overexpression of hurpin mRNA in psoriasis, squamous cell carcinoma (SCC), and actinic keratosis. In contrast, expression of hurpin in melanoma and basal cell carcinoma was comparable to that in normal skin. Overall, the strongest overexpression was observed in SCC and psoriasis. Individual differences in hurpin expression between patients were observed. The increased expression and redistribution of hurpin in diseased skin suggests its possible involvement in inflammatory processes or the regulation of endogenous or pathogen‐derived proteinase activity. Additional studies will elucidate the physiological role of hurpin.
Non‐lesional vitiliginous melanocytes are not characterized by an increased proneness to nitric oxide‐induced apoptosis
Authors: Ivanova Krassimira , Van Den Wijngaard Rene , Gerzer Rupert , Lamers Wouter H. , Das Pranab K.
Published: May 2005

Abstract:  Nitric oxide (NO) is a reactive endogenous molecule with multiple functions including inflammation and immunity. NO stimulates melanogenesis by activating soluble guanylyl cyclase (sGC) resulting in increases in intracellular guanosine 3′,5′‐cyclic monophosphate (cGMP). In vitro experiments showed that NO could inhibit the de novo attachment of melanocytes to extracellular matrix (ECM) suggesting that NO‐induced aberrant perturbation of melanocyte–ECM interaction could be a reason for melanocyte loss in vitiliginous lesions. Here, we examined whether there might be differences between normal melanocytes and vitiliginous melanocytes (VMs) with respect to NO‐induced detachment from ECM and whether cGMP is involved. We used the direct NO donor (Z)‐1‐[N‐(3‐ammoniopropyl)‐N‐(n‐propyl)amino]diazen‐1‐ium‐1,2‐diolate and the peroxynitrite donor 3‐morpholino‐sydnonimine for the present studies. These donors induced detachment of both normal melanocytes and non‐lesional VMs in a time‐ and concentration‐dependent manner with comparable susceptibility and similar expression profile of sGC. Treatment of melanocytes with caspase inhibitors reduced cell detachment, indicating that a major part of the detachment is due to apoptosis. The NO‐induced detachment but not apoptosis was partly inhibited in the presence of sGC and cGMP‐dependent protein kinase inhibitors. In addition, the membrane‐permeable cGMP analog 8‐(4‐chlorophenyethio/guanosine‐3′,5′‐cyclic monophosphate (PCPT) cGMP was not able to induce apoptosis in melanocytes, suggesting that NO‐induced detachment of melanocytes via apoptosis is cGMP‐independent. The present results also indicate that there are no apparent differences between NO‐induced detachment of non‐lesional vitiliginous and normal melanocytes from ECM.
Grain Size Distributions and Strength Variability of High‐Purity Alumina
Authors: Kovar Desiderio , Readey Michael J.
Published: May 2005

Two batches of high‐purity, alumina ceramics having an equiaxed grain morphology were manufactured with a mean grain size of approximately 10 μm. A low‐temperature heat treatment performed prior to sintering on one batch of specimens resulted in a narrow grain size distribution. The other batch of specimens was fired in a conventional manner and exhibited a broader grain size distribution. Mechanical tests performed on these specimens indicated little difference in the flaw tolerance of T‐curve behavior of the aluminas, despite the presence of coarser grains in the conventionally fired alumina. Observations of cracks in these high‐purity aluminas revealed that large grains ruptured transgranularly and therefore did not act as effective bridging sites. Strength tests on polished specimens indicated that the alumina with the broad grain size distribution exhibited greater strength variability than the alumina with a narrow grain size distribution. A simple analysis shows that, because of the shallow T‐curve behavior observed in both aluminas, stable crack extension should not occur from natural flaws. The strength of these high‐purity aluminas is therefore controlled by the initial flaw size and the initial toughness. The increased strength variability in the alumina with the broad grain size distribution is rationalized in terms of a wider distribution of critical flaws.
Estimation of Hamaker Constants of Ceramic Materials from Optical Data Using Lifshitz Theory
Authors: Bergstrom Lennart , Meurk Anders , Arwin Hans , Rowcliffe David J.
Published: May 2005

The Hamaker constants of eight different ceramic materials, 6H‐SiC, tetragonal, partially stabilized ZrO2 (3% Y2O3), β‐Si3N4, α‐Al2O3, Y2O3, sapphire (single‐crystal α‐Al2O3), MgO, MgAl2O4, and fused silica, across air, water, and n‐dodecane at room temperature and across silica at 2000 K have been calculated from optical data using the Lifshitz theory. Spectroscopic ellipsometry was used to measure the photon energy dependence of the refractive index, n, and the extinction coefficient, k, in the visible and near‐UV range on several important ceramic materials. This relatively simple, nondestructive technique has proved to yield reliable optical data on sintered, polycrystalline materials such as Si3N4, SiC, ZrO2, Al2O3, and ZnO. For the other materials, Y2O3, sapphire, MgO, MgAl2O4, and fused silica, optical data from the literature were used to calculate the Hamaker constants. The calculated Hamaker constants were estimated to be accurate within ±10%.