bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent
Authors: Kearley Jennifer , Barker Jane E. , Robinson Douglas S. , Lloyd Clare M.
Published: November 2005

Deficient suppression of T cell responses to allergen by CD4+CD25+ regulatory T cells has been observed in patients with allergic disease. Our current experiments used a mouse model of airway inflammation to examine the suppressive activity of allergen-specific CD4+CD25+ T cells in vivo. Transfer of ovalbumin (OVA) peptide–specific CD4+CD25+ T cells to OVA-sensitized mice reduced airway hyperreactivity (AHR), recruitment of eosinophils, and T helper type 2 (Th2) cytokine expression in the lung after allergen challenge. This suppression was dependent on interleukin (IL) 10 because increased lung expression of IL-10 was detected after transfer of CD4+CD25+ T cells, and regulation was reversed by anti–IL-10R antibody. However, suppression of AHR, airway inflammation, and increased expression of IL-10 were still observed when CD4+CD25+ T cells from IL-10 gene–deficient mice were transferred. Intracellular cytokine staining confirmed that transfer of CD4+CD25+ T cells induced IL-10 expression in recipient CD4+ T cells, but no increase in IL-10 expression was detected in airway macrophages, dendritic cells, or B cells. These data suggest that CD4+CD25+ T cells can suppress the Th2 cell–driven response to allergen in vivo by an IL-10–dependent mechanism but that IL-10 production by the regulatory T cells themselves is not required for such suppression.
Endomucin, a CD34-like sialomucin, marks hematopoietic stem cells throughout development
Authors: Matsubara Azusa , Iwama Atsushi , Yamazaki Satoshi , Furuta Chie , Hirasawa Ryutaro , Morita Yohei , Osawa Mitsujiro , Motohashi Tsutomu , Eto Koji , Ema Hideo , Kitamura Toshio , Vestweber Dietmar , Nakauchi Hiromitsu
Published: November 2005

To detect as yet unidentified cell-surface molecules specific to hematopoietic stem cells (HSCs), a modified signal sequence trap was successfully applied to mouse bone marrow (BM) CD34−c-Kit+Sca-1+Lin− (CD34−KSL) HSCs. One of the identified molecules, Endomucin, is an endothelial sialomucin closely related to CD34. High-level expression of Endomucin was confined to the BM KSL HSCs and progenitor cells, and, importantly, long-term repopulating (LTR)–HSCs were exclusively present in the Endomucin+CD34−KSL population. Notably, in the yolk sac, Endomucin expression separated multipotential hematopoietic cells from committed erythroid progenitors in the cell fraction positive for CD41, an early embryonic hematopoietic marker. Furthermore, developing HSCs in the intraembryonic aorta-gonad-mesonephros (AGM) region were highly enriched in the CD45−CD41+Endomucin+ fraction at day 10.5 of gestation (E10.5) and in the CD45+CD41+Endomucin+ fraction at E11.5. Detailed analyses of these fractions uncovered drastic changes in their BM repopulating capacities as well as in vitro cytokine responsiveness within this narrow time frame. Our findings establish Endomucin as a novel cell-surface marker for LTR-HSCs throughout development and provide a powerful tool in understanding HSC ontogeny.
Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity
Authors: Zajonc Dirk M. , Maricic Igor , Wu Douglass , Halder Ramesh , Roy Keshab , Wong Chi-Huey , Kumar Vipin , Wilson Ian A.
Published: November 2005

Sulfatide derived from the myelin stimulates a distinct population of CD1d-restricted natural killer T (NKT) cells. Cis-tetracosenoyl sulfatide is one of the immunodominant species in myelin as identified by proliferation, cytokine secretion, and CD1d tetramer staining. The crystal structure of mouse CD1d in complex with cis-tetracosenoyl sulfatide at 1.9 Å resolution reveals that the longer cis-tetracosenoyl fatty acid chain fully occupies the A′ pocket of the CD1d binding groove, whereas the sphingosine chain fills up the F′ pocket. A precise hydrogen bond network in the center of the binding groove orients and positions the ceramide backbone for insertion of the lipid tails in their respective pockets. The 3′-sulfated galactose headgroup is highly exposed for presentation to the T cell receptor and projects up and away from the binding pocket due to its β linkage, compared with the more intimate binding of the α-glactosyl ceramide headgroup to CD1d. These structure and binding data on sulfatide presentation by CD1d have important implications for the design of therapeutics that target T cells reactive for myelin glycolipids in autoimmune diseases of the central nervous system.
Long Polyamines Act as Cofactors in PIP2 Activation of Inward Rectifier Potassium (Kir2.1) Channels
Authors: Xie Lai-Hua , John Scott A. , Ribalet Bernard , Weiss James N.
Published: November 2005

Phosphatidylinosital-4,5-bisphosphate (PIP2) acts as an essential factor regulating the activity of all Kir channels. In most Kir members, the dependence on PIP2 is modulated by other factors, such as protein kinases (in Kir1), Gβγ (in Kir3), and the sulfonylurea receptor (in Kir6). So far, however, no regulator has been identified in Kir2 channels. Here we show that polyamines, which cause inward rectification by selectively blocking outward current, also regulate the interaction of PIP2 with Kir2.1 channels to maintain channel availability. Using spermine and diamines as polyamine analogs, we demonstrate that both spontaneous and PIP2 antibody–induced rundown of Kir2.1 channels in excised inside-out patches was markedly slowed by long polyamines; in contrast, polyamines with shorter chain length were ineffective. In K188Q mutant channels, which have a low PIP2 affinity, application PIP2 (10 μM) was unable to activate channel activity in the absence of polyamines, but markedly activated channels in the presence of long diamines. Using neomycin as a measure of PIP2 affinity, we found that long polyamines were capable of strengthening either the wild type or K188Q channels' interaction with PIP2. The negatively charged D172 residue inside the transmembrane pore region was critical for the shift of channel–PIP2 binding affinity by long polyamines. Sustained pore block by polyamines was neither sufficient nor necessary for this effect. We conclude that long polyamines serve a dual role as both blockers and coactivators (with PIP2) of Kir2.1 channels.
A Unique Voltage Sensor Sensitizes the Potassium Channel AKT2 to Phosphoregulation
Authors: Michard Erwan , Lacombe Benoît , Porée Fabien , Mueller-Roeber Bernd , Sentenac Hervé , Thibaud Jean-Baptiste , Dreyer Ingo
Published: November 2005

Among all voltage-gated K+ channels from the model plant Arabidopsis thaliana, the weakly rectifying K+ channel (Kweak channel) AKT2 displays unique gating properties. AKT2 is exceptionally regulated by phosphorylation: when nonphosphorylated AKT2 behaves as an inward-rectifying potassium channel; phosphorylation of AKT2 abolishes inward rectification by shifting its activation threshold far positive (>200 mV) so that it closes only at voltages positive of +100 mV. In its phosphorylated form, AKT2 is thus locked in the open state in the entire physiological voltage range. To understand the molecular grounds of this unique gating behavior, we generated chimeras between AKT2 and the conventional inward-rectifying channel KAT1. The transfer of the pore from KAT1 to AKT2 altered the permeation properties of the channel. However, the gating properties were unaffected, suggesting that the pore region of AKT2 is not responsible for the unique Kweak gating. Instead, a lysine residue in S4, highly conserved among all Kweak channels but absent from other plant K+ channels, was pinpointed in a site-directed mutagenesis approach. Substitution of the lysine by serine or aspartate abolished the “open-lock” characteristic and converted AKT2 into an inward-rectifying channel. Interestingly, phosphoregulation of the mutant AKT2-K197S appeared to be similar to that of the Kin channel KAT1: as suggested by mimicking the phosphorylated and dephosphorylated states, phosphorylation induced a shift of the activation threshold of AKT2-K197S by about +50 mV. We conclude that the lysine residue K197 sensitizes AKT2 to phosphoregulation. The phosphorylation-induced reduction of the activation energy in AKT2 is ∼6 kT larger than in the K197S mutant. It is discussed that this hypersensitive response of AKT2 to phosphorylation equips a cell with the versatility to establish a potassium gradient and to make efficient use of it.
On the improvement of the metrological properties of manganin sensors
Authors: Rostocki Aleksander J , Urbański Michał K , Wiśniewski Roland , Wilczyńska Teresa
Published: November 2005

The paper presents the recent progress made in the accuracy improvement of the manganin pressure sensors at the Warsaw University of Technology (WUT) and at the Institute of Nuclear Energy. The efforts of the authors were concentrated on three problems:

(1) The improvement of the temperature characteristics by the design of a manganin sensor with the temperature compensation achieved by the application of two manganin coils with two different temperature characteristics;

(2) The improvement of the calibration process by

- (a) using a high pressure deadweight piston gauge (with the correction of effective area versus pressure dependence, built at WUT),

- (b) measurements of the manganin resistance as a function of the temperature and of the pressure using a precise multimeter and

- (c) application of statistical methods for long series of measurements.

(3) The modification of the thermal characteristic by implantation of bismuth and krypton ions.
Extracellular Signal-regulated Kinase Regulates Clathrin-independent Endosomal Trafficking
Authors: Robertson Sarah E. , Setty Subba Rao Gangi , Sitaram Anand , Marks Michael S. , Lewis Robert E. , Chou Margaret M.
Published: November 2005

Extracellular signal-regulated kinase (Erk) is widely recognized for its central role in cell proliferation and motility. Although previous work has shown that Erk is localized at endosomal compartments, no role for Erk in regulating endosomal trafficking has been demonstrated. Here, we report that Erk signaling regulates trafficking through the clathrin-independent, ADP-ribosylation factor 6 (Arf6) GTPase-regulated endosomal pathway. Inactivation of Erk induced by a variety of methods leads to a dramatic expansion of the Arf6 endosomal recycling compartment, and intracellular accumulation of cargo, such as class I major histocompatibility complex, within the expanded endosome. Treatment of cells with the mitogen-activated protein kinase kinase (MEK) inhibitor U0126 reduces surface expression of MHCI without affecting its rate of endocytosis, suggesting that inactivation of Erk perturbs recycling. Furthermore, under conditions where Erk activity is inhibited, a large cohort of Erk, MEK, and the Erk scaffold kinase suppressor of Ras 1 accumulates at the Arf6 recycling compartment. The requirement for Erk was highly specific for this endocytic pathway, because its inhibition had no effect on trafficking of cargo of the classical clathrin-dependent pathway. These studies reveal a previously unappreciated link of Erk signaling to organelle dynamics and endosomal trafficking.
Interaction of Hsp90 with Ribosomal Proteins Protects from Ubiquitination and Proteasome-dependent Degradation
Authors: Kim Tae-Sung , Jang Chang-Young , Kim Hag Dong , Lee Jae Yung , Ahn Byung-Yoon , Kim Joon
Published: November 2005

Heat-shock protein 90 (Hsp90) is a molecular chaperone that plays a key role in the conformational maturation of various transcription factors and protein kinases in signal transduction. Multifunctional ribosomal protein S3 (rpS3), a component of the ribosomal small subunit, is involved in DNA repair and apoptosis. Our data show that Hsp90 binds directly to rpS3 and the functional consequence of Hsp90-rpS3 interaction results in the prevention of the ubiquitination and the proteasome-dependent degradation of rpS3, subsequently retaining the function and the biogenesis of the ribosome. Interference of Hsp90 activity by Hsp90 inhibitors appears to dissociate rpS3 from Hsp90, associate the protein with Hsp70, and induce the degradation of free forms of rpS3. Furthermore, ribosomal protein S6 (rpS6) also interacted with Hsp90 and exhibited a similar effect upon treatment with Hsp90 inhibitors. Therefore, we conclude that Hsp90 regulates the function of ribosomes by maintaining the stability of 40S ribosomal proteins such as rpS3 and rpS6.
A primitive protostegid from Australia and early sea turtle evolution
Authors: Kear Benjamin P , Lee Michael S.Y
Published: November 2005

Sea turtles (Chelonioidea) are a prominent group of modern marine reptiles whose early history is poorly understood. Analysis of exceptionally well preserved fossils of
Bouliachelys suteri
gen. et sp. nov., a large-bodied basal protostegid (primitive chelonioid) from the Early Cretaceous (Albian) of Australia, indicates that early sea turtles were both larger and more diverse than previously thought. The analysis implies at least five distinct sea turtle lineages existed around 100 million years ago. Currently, the postcranially primitive
Ctenochelys
and
Toxochelys
are interpreted as crown-group sea turtles closely related to living cheloniids (e.g.
Chelonia
); in contrast, the new phylogeny suggests that they are transitional (intermediate stem-taxa) between continental testudines and derived, pelagic chelonioids.
Larval development and settlement of a whale barnacle
Authors: Nogata Yasuyuki , Matsumura Kiyotaka
Published: November 2005

Larval development and settlement of whale barnacles have not previously been described, unlike intertidal barnacles. Indeed, the mechanisms of the association between barnacles and whales have not been studied. Here we describe the larval development and settlement of the whale barnacle,
Coronula diadema
, and possible involvement of a cue from the host in inducing larval settlement. Eight-cell stage embryos were collected from
C. diadema
on a stranded humpback whale, incubated in filtered seawater for 7 days, and nauplius larvae hatched out. When fed with
Chaetoceros gracilis
, the nauplii developed to stage VI, and finally metamorphosed to the cypris stage. The larval development looked similar to that of intertidal barnacles with planktotrophic larval stages. The cyprids did not settle in normal seawater, but did settle in polystyrene Petri dishes when incubated in seawater with a small piece of skin tissue from the host whale. This strongly suggests the involvement of a chemical cue from the host whale tissue to induce larval settlement.
Genetic evidence for female-biased dispersal and gene flow in a polygynous primate
Authors: Hammond Robert L , Lawson Handley Lori J , Winney Bruce J , Bruford Michael W , Perrin Nicolas
Published: November 2005

Many models of sex-biased dispersal predict that the direction of sex-bias depends upon a species' mating system. In agreement with this, almost all polygynous mammals show male-biased dispersal whereas largely monogamous birds show female-biased dispersal (FBD). The hamadryas baboon (Papio hamadryas hamadryas) is polygynous and so dispersal is predicted to be male biased, as is found in all other baboon subspecies, but there are conflicting field data showing both female and male dispersal. Using 19 autosomal genetic markers genotyped in baboons from four Saudi Arabian populations, we found strong evidence for FBD in post-dispersal adults but not, as expected, in pre-dispersal infants and young juveniles, when we compared male and female: population structure (Fst), inbreeding (Fis), relatedness (r), and the mean assignment index (mAIc). Furthermore, we found evidence for female-biased gene flow as population genetic structure (Fst), was about four times higher for the paternally inherited Y, than for either autosomal markers or for maternally inherited mtDNA. These results contradict the direction of sex-bias predicted by the mating system and show that FBD has evolved recently from an ancestral state of male-biased dispersal. We suggest that the cost–benefit balance of dispersal to males and females is tightly linked to the unique hierarchical social structure of hamadryas baboons and that dispersal and social organization have coevolved.
Spatial ecology of mating success in a sexually polymorphic plant
Authors: Stehlik Ivana , Caspersen John P , Barrett Spencer C.H
Published: November 2005

The spatial context of reproduction is of crucial importance to plants because of their sessile habit. Since pollen and seed dispersal is often restricted, mating success is likely to depend on the quantity and quality of mates in local neighbourhoods. Here we use neighbourhood models to investigate the spatial ecology of pollination and mating in
Narcissus assoanus
, a sexually polymorphic plant with two mating morphs that differ in style length. By mapping individuals in eight populations from southwestern France, we investigated the influence of the density and morph identity of plants at different spatial scales on variation in female fertility. By using inferences on the expected patterns of pollen transfer based on floral morphology, we were able to predict the quantitative relations between local morph ratios and variation in fertility. Our analyses revealed differences in the spatial clustering of morphs and in their response to plant density and morph identity within local neighbourhoods. Mating success in
N. assoanus
was characterized by both density- and frequency-dependent processes, a condition that may be a general feature of the spatial ecology of plant mating.
Coprophagy in a cave-adapted salamander; the importance of bat guano examined through nutritional and stable isotope analyses
Authors: Fenolio Danté B , Graening G.O , Collier Bret A , Stout Jim F
Published: November 2005

During a two year population ecology study in a cave environment, 15Eurycea(=Typhlotriton)spelaeawere observed ingesting bat guano. Furthermore,E. spelaeacapture numbers increased significantly during the time that grey bats (Myotis grisescens) deposited fresh guano. We investigated the hypothesis that this behaviour was not incidental to the capture of invertebrate prey, but a diet switch to an energy-rich detritus in an oligotrophic environment. Stable isotope assays determined that guano may be assimilated into salamander muscle tissue, and nutritional analyses revealed that guano is a comparable food source to potential invertebrate prey items. This is the first report of coprophagy in a salamander and in any amphibian for reasons other than intestinal inoculation. Because many temperate subterranean environments are often energy poor and this limitation is thought to select for increased diet breadth, we predict that coprophagy may be common in subterranean vertebrates where it is not currently recognized.
Interactions between predator- and diet-induced phenotypic changes in body shape of crucian carp
Authors: Andersson Jens , Johansson Frank , Söderlund Tony
Published: November 2005

Predator cues and diet, when studied separately, have been shown to affect body shape of organisms. Previous studies show that the morphological responses to predator absence/presence and diet may be similar, and hence could confound the interpretation of the causes of morphological differences found between groups of individuals. In this study, we simultaneously examined the effect of these two factors on body shape and performance in crucian carp in a laboratory experiment. Crucian carp (Carassius carassius) developed a shallow body shape when feeding on zooplankton prey and a deep body shape when feeding on benthic chironomids. In addition, the presence of chemical cues from a pike predator affected body shape, where a shallow body shape was developed in the absence of pike and a deep body shape was developed in the presence of pike. Foraging activity was low in the presence of pike cues and when chironomids were given as prey. Our results thereby suggest that the change in body shape could be indirectly mediated through differences in foraging activity. Finally, the induced body shape changes affected the foraging efficiency, where crucians raised on a zooplankton diet or in the absence of pike cues had a higher foraging success on zooplankton compared to crucian raised on a chironomid diet or in the presence of pike. These results suggest that body changes in response to predators can be associated with a cost, in terms of competition for resources.
A critique of directionality theory
Authors: Bulmer Michael
Published: November 2005

Directionality theory suggests that demographic entropy, defined in a way analogous to thermodynamic entropy, is as important as the Malthusian parameter in determining life history evolution in an age-structured population. In particular, it suggests that entropy should increase in equilibrium species and decrease in opportunistic species. This theory has been applied to explain the evolution of body size and of senescence. It has been claimed recently that this theory has been validated by a simulation study, but it is argued here that this study reveals substantial flaws in directionality theory and that the Malthusian parameter rather than entropy is the appropriate tool in the study of life history evolution.
A shift to parasitism in the jellyfish symbiont
Symbiodinium microadriaticum
Authors: Sachs Joel L , Wilcox Thomas P
Published: November 2005

One of the outstanding and poorly understood examples of cooperation between species is found in corals, hydras and jellyfish that form symbioses with algae. These mutualistic algae are mostly acquired infectiously from the seawater and, according to models of virulence evolution, should be selected to parasitize their hosts. We altered algal transmission between jellyfish hosts in the laboratory to examine the potential for virulence evolution in this widespread symbiosis. In one experimental treatment, vertical transmission of algae (parent to offspring) selected for symbiont cooperation, because symbiont fitness was tied to host reproduction. In the other treatment, horizontal transmission (infectious spread) decoupled symbiont fitness from the host, potentially allowing parasitic symbionts to spread. Fitness estimates revealed a striking shift to parasitism in the horizontal treatment. The horizontally transmitted algae proliferated faster within hosts and had higher dispersal rates from hosts compared to the vertical treatment, while reducing host reproduction and growth. However, a trade-off was detected between harm caused to hosts and symbiont fitness. Virulence trade-offs have been modelled for pathogens and may be critical in stabilising ‘infectious’ symbioses. Our results demonstrate the dynamic nature of this symbiosis and illustrate the potential ease with which beneficial symbionts can evolve into parasites.
Preservation of hypericin and related polycyclic quinone pigments in fossil crinoids
Authors: Wolkenstein Klaus , Gross Jürgen H , Falk Heinz , Schöler Heinz F
Published: November 2005

The fringelite pigments, a group of phenanthroperylene quinones discovered in purple coloured specimens of the Upper Jurassic crinoid
Liliocrinus
, demonstrate exceptional preservation of organic compounds in macrofossils. Here we report the finding of hypericin and related phenanthroperylene quinones in
Liliocrinus munsterianus
from the original ‘Fringeli’ locality and in the Middle Triassic crinoid
Carnallicrinus carnalli
. Our results show that fringelites in fact consist of hypericin and closely related derivatives and that the stratigraphic range of phenanthroperylene quinones is much wider than previously known. The fossil occurrence of hypericin indicates a polyketide biosynthesis of hypericin-type pigments in Mesozoic crinoids analogous to similar polyketides, which occur in living crinoids. The common presence of a characteristic distribution pattern of the fossil pigments and related polycyclic aromatic hydrocarbons further suggests that this assemblage is the result of a stepwise degradation of hypericin via a general diagenetic pathway.
Coincident scales of forest feedback on climate and conservation in a diversity hot spot
Authors: Webb Thomas J , Gaston Kevin J , Hannah Lee , Ian Woodward F
Published: November 2005

The dynamic relationship between vegetation and climate is now widely acknowledged. Climate influences the distribution of vegetation; and through a number of feedback mechanisms vegetation affects climate. This implies that land-use changes such as deforestation will have climatic consequences. However, the spatial scales at which such feedbacks occur remain largely unknown. Here, we use a large database of precipitation and tree cover records for an area of the biodiversity-rich Atlantic forest region in south eastern Brazil to investigate the forest–rainfall feedback at a range of spatial scales fromca101–104 km2. We show that the strength of the feedback increases up to scales of at least 103 km2, with the climate at a particular locality influenced by the pattern of landcover extending over a large area. Thus, smaller forest fragments, even if well protected, may suffer degradation due to the climate responding to land-use change in the surrounding area. Atlantic forest vertebrate taxa also require large areas of forest to support viable populations. Areas of forest ofca103 km2would be large enough to support such populations at the same time as minimizing the risk of climatic feedbacks resulting from deforestation.
All wet or dried up? Real differences between aquatic and terrestrial food webs
Authors: Shurin Jonathan B , Gruner Daniel S , Hillebrand Helmut
Published: November 2005

Ecologists have greatly advanced our understanding of the processes that regulate trophic structure and dynamics in ecosystems. However, the causes of systematic variation among ecosystems remain controversial and poorly elucidated. Contrasts between aquatic and terrestrial ecosystems in particular have inspired much speculation, but only recent empirical quantification. Here, we review evidence for systematic differences in energy flow and biomass partitioning between producers and herbivores, detritus and decomposers, and higher trophic levels. The magnitudes of different trophic pathways vary considerably, with less herbivory, more decomposers and more detrital accumulation on land. Aquatic–terrestrial differences are consistent across the global range of primary productivity, indicating that structural contrasts between the two systems are preserved despite large variation in energy input. We argue that variable selective forces drive differences in plant allocation patterns in aquatic and terrestrial environments that propagate upward to shape food webs. The small size and lack of structural tissues in phytoplankton mean that aquatic primary producers achieve faster growth rates and are more nutritious to heterotrophs than their terrestrial counterparts. Plankton food webs are also strongly size-structured, while size and trophic position are less strongly correlated in most terrestrial (and many benthic) habitats. The available data indicate that contrasts between aquatic and terrestrial food webs are driven primarily by the growth rate, size and nutritional quality of autotrophs. Differences in food-web architecture (food chain length, the prevalence of omnivory, specialization or anti-predator defences) may arise as a consequence of systematic variation in the character of the producer community.
The principles of collective animal behaviour
Authors: Sumpter D.J.T
Published: November 2005

In recent years, the concept of self-organization has been used to understand collective behaviour of animals. The central tenet of self-organization is that simple repeated interactions between individuals can produce complex adaptive patterns at the level of the group. Inspiration comes from patterns seen in physical systems, such as spiralling chemical waves, which arise without complexity at the level of the individual units of which the system is composed. The suggestion is that biological structures such as termite mounds, ant trail networks and even human crowds can be explained in terms of repeated interactions between the animals and their environment, without invoking individual complexity. Here, I review cases in which the self-organization approach has been successful in explaining collective behaviour of animal groups and societies. Ant pheromone trail networks, aggregation of cockroaches, the applause of opera audiences and the migration of fish schools have all been accurately described in terms of individuals following simple sets of rules. Unlike the simple units composing physical systems, however, animals are themselves complex entities, and other examples of collective behaviour, such as honey bee foraging with its myriad of dance signals and behavioural cues, cannot be fully understood in terms of simple individuals alone. I argue that the key to understanding collective behaviour lies in identifying the principles of the behavioural algorithms followed by individual animals and of how information flows between the animals. These principles, such as positive feedback, response thresholds and individual integrity, are repeatedly observed in very different animal societies. The future of collective behaviour research lies in classifying these principles, establishing the properties they produce at a group level and asking why they have evolved in so many different and distinct natural systems. Ultimately, this research could inform not only our understanding of animal societies, but also the principles by which we organize our own society.
Nature's green revolution: the remarkable evolutionary rise of C4plants
Authors: Osborne Colin P , Beerling David J
Published: November 2005

Plants with the C4photosynthetic pathway dominate today's tropical savannahs and grasslands, and account for some 30% of global terrestrial carbon fixation. Their success stems from a physiological CO2-concentrating pump, which leads to high photosynthetic efficiency in warm climates and low atmospheric CO2concentrations. Remarkably, their dominance of tropical environments was achieved in only the past 10 million years (Myr), less than 3% of the time that terrestrial plants have existed on Earth. We critically review the proposal that declining atmospheric CO2triggered this tropical revolution via its effects on the photosynthetic efficiency of leaves. Our synthesis of the latest geological evidence from South Asia and North America suggests that this emphasis is misplaced. Instead, we find important roles for regional climate change and fire in South Asia, but no obvious environmental trigger for C4success in North America. CO2-starvation is implicated in the origins of C4plants 25–32 Myr ago, raising the possibility that the pathway evolved under more extreme atmospheric conditions experienced 10 times earlier. However, our geochemical analyses provide no evidence of the C4mechanism at this time, although possible ancestral components of the C4pathway are identified in ancient plant lineages. We suggest that future research must redress the substantial imbalance between experimental investigations and analyses of the geological record.
Longevity and ageing: appraising the evolutionary consequences of growing old
Authors: Bonsall Michael B
Published: November 2005

Senescence or ageing is an increase in mortality and/or decline in fertility with increasing age. Evolutionary theories predict that ageing or longevity evolves in response to patterns of extrinsic mortality or intrinsic damage. If ageing is viewed as the outcome of the processes of behaviour, growth and reproduction then it should be possible to predict mortality rate. Recent developments have shown that it is now possible to integrate these ecological and physiological processes and predict the shape of mortality trajectories. By drawing on the key exciting developments in the cellular, physiological and ecological process of longevity the evolutionary consequences of ageing are reviewed. In presenting these ideas an evolutionary demographic framework is used to argue how trade-offs in life-history strategies are important in the maintenance of variation in longevity within and between species. Evolutionary processes associated with longevity have an important role in explaining levels of biological diversity and speciation. In particular, the effects of life-history trait trade-offs in maintaining and promoting species diversity are explored. Such trade-offs can alleviate the effects of intense competition between species and promote species coexistence and diversification. These results have important implications for understanding a number of core ecological processes such as how species are divided among niches, how closely related species co-occur and the rules by which species assemble into food-webs. Theoretical work reveals that the proximate physiological processes are as important as the ecological factors in explaining the variation in the evolution of longevity. Possible future research challenges integrating work on the evolution and mechanisms of growing old are briefly discussed.
How do genes regulate simple behaviours? Understanding how different neurons in the vertebrate spinal cord are genetically specified
Authors: Lewis Katharine E
Published: November 2005

Understanding how the vertebrate central nervous system develops and functions is a major goal of a large body of biological research. This research is driven both by intellectual curiosity about this amazing organ that coordinates our conscious and unconscious bodily processes, perceptions and actions and by the practical desire to develop effective treatments for people with spinal cord injuries or neurological diseases. In recent years, we have learnt an impressive amount about how the nerve cells that communicate with muscles, motoneurons, are made in a developing embryo and this knowledge has enabled researchers to grow motoneurons from stem cells. Building on the success of these studies, researchers have now started to unravel how most of the other nerve cells in the spinal cord are made and function. This review will describe what we currently know about spinal cord nerve cell development, concentrating on the largest category of nerve cells, which are called interneurons. I will then discuss how we can build and expand upon this knowledge base to elucidate the complete genetic programme that determines how different spinal cord nerve cells are made and connected up into neural circuits with particular functions.
Complexities and uncertainties of neuronal network function
Authors: Parker David
Published: November 2005

The nervous system generates behaviours through the activity in groups of neurons assembled into networks. Understanding these networks is thus essential to our understanding of nervous system function.

Understanding a network requires information on its component cells, their interactions and their functional properties. Few networks come close to providing complete information on these aspects. However, even if complete information were available it would still only provide limited insight into network function. This is because the functional and structural properties of a network are not fixed but are plastic and can change over time. The number of interacting network components, their (variable) functional properties, and various plasticity mechanisms endows networks with considerable flexibility, but these features inevitably complicate network analyses.

This review will initially discuss the general approaches and problems of network analyses. It will then examine the success of these analyses in a model spinal cord locomotor network in the lamprey, to determine to what extent in this relatively simple vertebrate system it is possible to claim detailed understanding of network function and plasticity.
Shelf‐margin clinoforms and prediction of deepwater sands
Authors: Johannessen Erik P. , Steel Ron J.
Published: November 2005

Early Eocene successions from Spitsbergen and offshore Ireland, showing well‐developed shelf‐margin clinoforms and a variety of deepwater sands, are used to develop models to predict the presence or absence of turbidite sands in clinoform strata without significant slope disturbance/ponding by salt or mud diapers. The studied clinoforms formed in front of narrow to moderate width (10–60 km) shelves and have slopes, 2–4°, that are typical of accreting shelf margins. The clinoforms are evaluated in terms of both shelf‐transiting sediment‐delivery systems and the resultant partitioning of the sand and mud budget along their different segments. Although this sediment‐budget partitioning is controlled by sediment type and flux, shelf width and gradient, process regime on the shelf and relative sea‐level behaviour, the most tell‐tale or predictive signs in the stratigraphic record appear to be (1) sediment‐delivery system type, (2) degree of shelf‐edge channelling and (3) character of shelf‐edge trajectory through time. The clinoform data sets from the Porcupine Basin (wells and 3‐D seismic) and from the Central Basin on Spitsbergen (outcrops) suggest that river‐dominated deltas are the most efficient delivery systems for dispersing sand into deep water beyond the shelf‐slope break. In addition, low‐angle or flat, channelled shelf‐edge trajectories associate with co‐eval deepwater slope and basin‐floor sands, whereas rising trajectories tend to associate with muddy slopes and basin floors. Characteristic features of the shelf‐edge, slope and basin‐floor segments of clinoforms for these trajectory types are documented. Seismic lines along the slope to basin‐floor transects tend to show apparent up‐dip sandstone pinchouts, but most of these are likely to be simply sidelap features. Dip lines aligned along the axes of sandy fairways show that stratigraphic traps are unlikely, unless slope channels become mud‐filled or are structurally partitioned. Another feature that is prominent in the data sets examined is the lack of slope onlap. During the relative rise of sea level back up to the shelf, the clinoform slopes are generally mud‐prone and they are characteristically aggradational.
Discrete‐element modelling of detachment folding
Authors: Hardy Stuart , Finch Emma
Published: November 2005

A two‐dimensional, discrete‐element modelling technique is used to investigate the initiation and growth of detachment folds in sedimentary rocks above a weak décollement level. The model depicts the sedimentary rocks as an assemblage of spheres that obey Newton's equations of motion and that interact with elastic forces under the influence of gravity. Faulting or fracturing between neighbouring elements is represented by a transition from repulsive–attractive forces to solely repulsive forces. The sedimentary sequence is mechanically heterogeneous, consisting of intercalated layers of markedly different strengths and thicknesses. The interlayering of weak and strong layers within the sedimentary rocks promotes the localization of flexural flow deformation within the weak layers. Even with simple displacement boundary conditions, and straightforward interlayering of weak and strong layers, the structural geometries that develop are complex, with a combination of box, lift‐off and disharmonic detachment fold styles forming above the décollement. In detail, it is found that the modelled folds grow by both limb rotation and limb lengthening. The combination of these two mechanisms results in uplift patterns above the folds that are difficult, or misleading, to interpret in terms of simple kinematic models. Comparison of modelling results with natural examples and with kinematic models highlights the complexities of structural interpretation in such settings.
Novel therapeutic strategies targeting growth factor signalling cascades in multiple myeloma
Authors: Yasui Hiroshi , Hideshima Teru , Richardson Paul G. , Anderson Kenneth C.
Published: November 2005

Multiple myeloma (MM) remains largely incurable despite conventional and high‐dose therapies, and novel biologically based treatment approaches are urgently required. Recent studies demonstrate that various growth factors including interleukin (IL)‐6, insulin‐like growth factor (IGF)‐1, vascular endothelial growth factor (VEGF), the tumour necrosis factor (TNF) family proteins, Wnt, and Notch family members play an important role in MM pathogenesis, and mediate tumour cell proliferation, drug resistance and migration in the bone marrow (BM) milieu. Targeting growth factors, therefore, represents a promising therapeutic strategy in MM. Novel agents inhibiting growth factor signalling cascades can target ligands, receptors, and/or downstream signalling cascade proteins in MM cells and the BM microenvironment. Combinations of these novel agents with conventional therapies may not only enhance cytotoxicity, but also avoid drug resistance and thereby improve patient outcome in MM.
Impaired interaction of α‐haemoglobin‐stabilising protein with α‐globin termination mutant in a yeast two‐hybrid system
Authors: Turbpaiboon Chairat , Limjindaporn Thawornchai , Wongwiwat Wiyada , U‐Pratya Yaowalak , Siritanaratkul Noppadol , Yenchitsomanus Pa‐thai , Jitrapakdee Sarawut , Wilairat Prapon
Published: November 2005

α‐Thalassaemia caused by α‐globin gene termination codon mutations (αT‐globin) has been explained by their inherent mRNA instability and by oxidative damage arising from the presence of membrane‐bound αT‐globin chains. To better understand the latter phenomenon, a yeast two‐hybrid system was used to assay the interaction between αT‐globin and its molecular chaperone, α‐haemoglobin‐stabilising protein (AHSP) and impaired binding of αT‐globin with AHSP compared with αwild‐type‐globin was observed.
Herpes simplex virus 1 infection induces the expression of proinflammatory cytokines, interferons and TLR7 in human corneal epithelial cells
Authors: Li Hui , Zhang Jing , Kumar Ashok , Zheng Mei , Atherton Sally S. , Yu Fu‐Shin X.
Published: November 2005

Herpetic epithelial and stromal keratitis is a sight‐threatening ocular infection. To study the role of the epithelium in the innate response to herpes simplex virus 1 (HSV‐1) infection of the cornea, we used a telomerase‐immortalized human corneal epithelial cell (HCEC) line, HUCL, and primary HCECs as a model and infected the cells with HSV‐1 (KOS strain). HSV‐1 infection of HCECs resulted in a two‐phase activation of nuclear factor‐kappaB (NF‐κB), JNK and p38, with the first peak at 1–4 hr and a second peak at 8 hr. Concomitant with the first peak of activation, transcriptional expression of interleukin (IL)‐6, IL‐8, tumour necrosis factor (TNF)‐α and interferon (IFN)‐β was rapidly induced in HSV‐1‐infected cells. HSV‐1 infection also induced the production of IL‐6, IL‐8, and TNF‐α in both HUCL cells and primary HCECs. Coincident with the second phase of NF‐κB activation in HSV‐1‐infected HCECs, the expression of Toll‐like receptor 7 (TLR7) was induced, whereas the level of TLR3 was greatly down‐regulated. Thus, in response to HSV‐1 infection, HCECs produce proinflammatory cytokines, leading to infiltration, and IFNs to enhance the antiviral activity in the cornea, probably through sequential activation of TLRs.
A canine model of cutaneous late‐phase reactions: prednisolone inhibition of cellular and cytokine responses
Authors: Pucheu‐Haston Cherie M. , Shuster Dale , Olivry Thierry , Brianceau Philippe , Lockwood Patrick , McClanahan Terrill , de Waal Malefyt Rene , Mattson Jeanine D. , Hammerberg Bruce
Published: November 2005

Immunoglobulin E (IgE)‐mediated late‐phase reactions can be induced in atopic humans by intradermal injection of relevant allergens or anti‐IgE antibodies. The histology of these reactions resembles that of naturally occurring atopic dermatitis. Strikingly similar responses can be induced in dogs, suggesting that a canine model could prove valuable for preclinical investigation of drugs targeting late‐phase reactions. This study was designed to characterize the cellular, cytokine and chemokine responses after intradermal anti‐IgE injection in untreated and prednisolone‐treated dogs. Normal beagles were untreated or treated with prednisolone before intradermal injection of polyclonal rabbit anti‐canine IgE or normal rabbit IgG. Biopsies were taken before injection and 6, 24 and 48 hr after injection. Samples were evaluated by histological and immunohistochemical staining, as well as by real‐time quantitative polymerase chain reaction analysis. Dermal eosinophil and neutrophil numbers increased dramatically within 6 hr after injection of rabbit anti‐canine IgE, and remained moderately elevated at 48 hr. The numbers of CD1c+ and CD3+ mononuclear cells were also increased at 6 hr. The real‐time quantitative polymerase chain reaction demonstrated marked increases in mRNA expression for interleukin‐13 (IL‐13), CCL2, CCL5 and CCL17. Levels of mRNA for IL‐2, IL‐4, IL‐6 and IFN‐γ did not change within the limits of detection. Prednisolone administration suppressed the influx of neutrophils, eosinophils, CD1c+ and CD3+ cells, as well as expression of IL‐13, CCL2, CCL5 and CCL17. These data document the cytokine and chemokine responses to anti‐IgE injection in canine skin, and they demonstrate the ability of the model to characterize the anti‐inflammatory effects of a known therapeutic agent.
A novel mechanism of nuclear factor‐κB regulation by adenoviral protein 14·7K
Authors: Carmody Ruaidhrí J. , Maguschak Kimberly , Chen Youhai H.
Published: November 2005

Viruses have evolved many different ways to evade immune attacks. The adenoviral E3 protein 14·7K effectively inhibits antiviral immunity and inflammation. However, the underlying mechanism for this effect is unclear. Here we show that 14·7K is a potent inhibitor of nuclear factor (NF)‐κB transcriptional activity following Toll‐like receptor (TLR) or tumour necrosis factor (TNF) receptor signalling. The inhibition of the NF‐κB activity occurs downstream of IκBα degradation and NF‐κB translocation into the nucleus. Analysis of NF‐κB DNA binding reveals that 14·7K specifically inhibits p50 homodimer DNA binding and that this inhibition is mediated through the interaction of 14·7K with p50. We propose that 14·7K inhibits NF‐κB activity through directly blocking p50 binding to DNA and that this is the basis for its anti‐inflammatory properties. Our data also indicate a role for p50 homodimer‐dependent transcription in inflammation.
Molecular characterization of an arthritogenic collagen peptide interacting with I‐Ar
Authors: Sakurai Yoshihiko , Tang Bo , Rosloniec Edward F. , Stuart John M. , Kang Andrew H. , Myers Linda K.
Published: November 2005

Collagen‐induced arthritis (CIA) is an autoimmune arthritis that can be elicited by the immunization of genetically susceptible strains of mice with type II collagen (CII). We have analysed the molecular interactions that occur between an arthritogenic T‐cell determinant CII (442–457) and the murine class II susceptibility allele I‐Ar. To determine which amino acid residues within the CII (442–457) sequence are responsible for binding to I‐Ar, a soluble I‐Ar : IgG2aFc fusion protein–peptide binding assay was developed. Various concentrations of analogue peptides were tested for their ability to compete with biotinylated CII (607–622) for binding to I‐Ar, thereby establishing a relative comparison of the binding affinities among these analogues. Analogue peptides with substitutions at positions 447 (Ala → Val), 448 (Gly → Ala) and 451 (Gly → Ala) bound poorly to the I‐Ar molecule. These data suggest that positions 447, 448 and 451 on CII are the major anchor points to I‐Ar molecules. In cytokine assays, only substitutions within positions 445–454 decreased the interferon‐γ production by T cells. These data narrow the core of the arthritogenic T‐cell determinant to CII (445–454). Identification of the molecular interactions involved in T‐cell recognition of CII should lead to antigen‐specific means of inhibiting autoimmune arthritis.