bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions and dynamics of the Shine–Dalgarno helix in the 70S ribosome
Authors: Korostelev Andrei , Trakhanov Sergei , Asahara Haruichi , Laurberg Martin , Lancaster Laura , Noller Harry F.
Published: October 2007

The crystal structure of an initiation-like 70S ribosome complex containing an 8-bp Shine–Dalgarno (SD) helix was determined at 3.8-Å resolution. Translation–libration–screw analysis showed that the inherent anisotropic motions of the SD helix were biased along its helical axis, suggesting that during the first step of translocation, the SD helix moves along its helical screw axis. Contacts between the SD helix and the ribosome were primarily through interactions with helices 23a, 26, and 28 of 16S rRNA. Contact with the neck (helix 28) of the 30S subunit near its hinge point suggests that formation of the SD helix could affect positioning of the head of the 30S subunit for optimal interaction with initiator tRNA. The bulged U723 in helix 23a interacts with the minor groove of the SD helix at the C1539·G-10 base pair, explaining its selective conservation in bacteria and archaea.
Neural correlates of a postponed decision report
Authors: Lemus Luis , Hernández Adrián , Luna Rogelio , Zainos Antonio , Nácher Verónica , Romo Ranulfo
Published: October 2007

Depending on environmental demands, a decision based on a sensory evaluation may be either immediately reported or postponed for later report. If postponed, the decision must be held in memory. But what exactly is stored by the underlying memory circuits, the final decision itself or the sensory information that led to it? Here, we report that, during a postponed decision report period, the activity of medial premotor cortex neurons encodes both the result of the sensory evaluation that corresponds to the monkey's possible choices and past sensory information on which the decision is based. These responses could switch back and forth with remarkable flexibility across the postponed decision report period. Moreover, these responses covaried with the animal's decision report. We propose that maintaining in working memory the original stimulus information on which the decision is based could serve to continuously update the postponed decision report in this task.
Immunotoxin and Taxol synergy results from a decrease in shed mesothelin levels in the extracellular space of tumors
Authors: Zhang Yujian , Xiang Laiman , Hassan Raffit , Pastan Ira
Published: October 2007

Recombinant immunotoxins are chimeric proteins composed of the Fv portion of a tumor-specific antibody fused to a toxin. SS1P (CAT-5001) is an immunotoxin composed of an antimesothelin Fv fused to a 38-kDa portion of
Pseudomonas
exotoxin A. Immunotoxins have been shown to be active in lymphomas and leukemias, but are much less active against solid tumors. We recently reported that Taxol and other chemotherapeutic agents show striking synergistic antitumor activity in mice when immunotoxin SS1P, which targets the mesothelin antigen on solid tumors, is given with Taxol. Using a pair of Taxol-sensitive and Taxol-resistant KB tumors equally sensitive to immunotoxin SS1P, we examined the mechanism of synergy. We show that synergy is only observed with Taxol-sensitive tumors, ruling out an effect of Taxol on endothelial cells. We also show that the KB tumors have high levels of shed mesothelin in their extracellular space; these levels increase with tumor size and, after Taxol treatment, dramatically fall in the drug-sensitive but not the drug-resistant tumors. Because the mesothelin levels in the tumor exceed the levels of SS1P in the tumor, and because shed mesothelin is being continuously released into the circulation at a high rate, we propose that synergy is due to the Taxol-induced fall in shed antigen levels.
Type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase regulates stress-induced apoptosis
Authors: Zou Jun , Marjanovic Jasna , Kisseleva Marina V. , Wilson Monita , Majerus Philip W.
Published: October 2007

A recently discovered phosphatidylinositol monophosphate, phosphatidylinositol 5-phosphate (PtdIns-5-P), plays an important role in nuclear signaling by influencing p53-dependent apoptosis. It interacts with a plant homeodomain finger of inhibitor of growth protein-2, causing an increase in the acetylation and stability of p53. Here we show that type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase (type I 4-phosphatase), an enzyme that dephosphorylates phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P
2
), forming PtdIns-5-P
in vitro
, can increase the cellular levels of PtdIns-5-P. When HeLa cells were treated with the DNA-damaging agents etoposide or doxorubicin, type I 4-phosphatase translocated to the nucleus and nuclear levels of PtdIns-5-P increased. This action resulted in increased p53 acetylation, which stabilized p53, leading to increased apoptosis. Overexpression of type I 4-phosphatase increased apoptosis, whereas RNAi of the enzyme diminished it. The half-life of p53 was shortened from 7 h to 1.8 h upon RNAi of type I 4-phosphatase. This enzyme therefore controls nuclear levels of PtdIns-5-P and thereby p53-dependent apoptosis.
Activation-dependent intrachromosomal interactions formed by theTNFgene promoter and two distal enhancers
Authors: Tsytsykova Alla V. , Rajsbaum Ricardo , Falvo James V. , Ligeiro Filipa , Neely Simon R. , Goldfeld Anne E.
Published: October 2007

Here we provide a mechanism for specific, efficient transcription of theTNFgene and, potentially, other genes residing within multigene loci. We identify and characterize highly conserved noncoding elements flanking theTNFgene, which undergo activation-dependent intrachromosomal interactions. These elements, hypersensitive site (HSS)−9 and HSS+3 (9 kb upstream and 3 kb downstream of theTNFgene, respectively), contain DNase I hypersensitive sites in naive, T helper 1, and T helper 2 primary T cells. Both HSS-9 and HSS+3 inducibly associate with acetylated histones, indicative of chromatin remodeling, bind the transcription factor nuclear factor of activated T cells (NFAT)pin vitroandin vivo, and function as enhancers of NFAT-dependent transactivation mediated by theTNFpromoter. Using the chromosome conformation capture assay, we demonstrate that upon T cell activation intrachromosomal looping occurs in theTNFlocus. HSS-9 and HSS+3 each associate with theTNFpromoter and with each other, circularizing theTNFgene and bringing NFAT-containing nucleoprotein complexes into close proximity.TNFgene regulation thus reveals a mode of intrachromosomal interaction that combines a looped gene topology with interactions between enhancers and a gene promoter.
Diminished adult neurogenesis in the marmoset brain precedes old age
Authors: Leuner Benedetta , Kozorovitskiy Yevgenia , Gross Charles G. , Gould Elizabeth
Published: October 2007

With aging there is a decline in the number of newly generated neurons in the dentate gyrus of the hippocampus. In rodents and tree shrews, this age-related decrease in neurogenesis is evident long before the animals become aged. No previous studies have investigated whether primates exhibit a similar decline in hippocampal neurogenesis with aging. To investigate this possibility, young to middle aged adult common marmosets (
Callithrix jacchus
) were injected with BrdU and perfused 3 weeks later. The number of newly generated cells in the subgranular zone/granule cell layer of the dentate gyrus was significantly lower in older animals and decreased linearly with age. A similar age-related decline in new cells was observed in the subventricular zone but not in the hilar region of the dentate gyrus. These data demonstrate that a substantial decrease in neurogenesis occurs before the onset of old age in the adult marmoset brain, suggesting the possibility that similar alterations occur in the human brain.
Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits
Authors: DiFiglia M. , Sena-Esteves M. , Chase K. , Sapp E. , Pfister E. , Sass M. , Yoder J. , Reeves P. , Pandey R. K. , Rajeev K. G. , Manoharan M. , Sah D. W. Y. , Zamore P. D. , Aronin N.
Published: October 2007

Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a CAG repeat in the
huntingtin
(
Htt
) gene. HD is autosomal dominant and, in theory, amenable to therapeutic RNA silencing. We introduced cholesterol-conjugated small interfering RNA duplexes (cc-siRNA) targeting human
Htt
mRNA (siRNA-
Htt
) into mouse striata that also received adeno-associated virus containing either expanded (100 CAG) or wild-type (18 CAG)
Htt
cDNA encoding huntingtin (Htt) 1–400. Adeno-associated virus delivery to striatum and overlying cortex of the mutant
Htt
gene, but not the wild type, produced neuropathology and motor deficits. Treatment with cc-siRNA-
Htt
in mice with mutant
Htt
prolonged survival of striatal neurons, reduced neuropil aggregates, diminished inclusion size, and lowered the frequency of clasping and footslips on balance beam. cc-siRNA-
Htt
was designed to target human wild-type and mutant
Htt
and decreased levels of both in the striatum. Our findings indicate that a single administration into the adult striatum of an siRNA targeting
Htt
can silence mutant
Htt
, attenuate neuronal pathology, and delay the abnormal behavioral phenotype observed in a rapid-onset, viral transgenic mouse model of HD.
A Fatal Case of Fulminant Hepatic Necrosis Following Sevoflurane Anesthesia
Authors: Turillazzi Emanuela , D’Errico Stefano , Neri Margherita , Riezzo Irene , Fineschi Vittorio
Published: October 2007

Volatile anesthetics can elevate cytosolic free Ca2+ by releasing calcium from internal calcium stores and uptaking calcium from extracellular medium. Sevoflurane is an inhaled anesthetic used worldwide. A clear understanding of the exact mechanism of hepatic injury induced by sevoflurane remains elusive. A 69-year-old man with preexisting mild renal dysfunction, having undergone sevoflurane general anesthesia twice in 2 days, developed moderate jaundice. Liver enzymes strongly increased and remained elevated until death, which occurred on the 6th day after the first surgical intervention. The microscopic liver examination revealed an extensive and confluent hepatic necrosis, characterised by a large amount of calcium deposition in hepatic cell cytoplasm. These data were confirmed by confocal laser scanning microscopy and a 3-D visualization of calcium depositions was evident in hepatocytes cytoplasm. Our findings are suggestive with the previous experimental reports that consider elevation of cytoplasmic calcium may be the basis of sevoflurane – induced hepatotoxicity.
2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) or Diethylstilbestrol (DES) Cause Similar Hematopoietic Hypocellularity and Hepatocellular Changes in Murine Fetal Liver, but Differentially Affect Gene Expression
Authors: Besteman Elizabeth G. , Zimmerman Kurt L. , Huckle William R. , Prater M. Renee , Gogal Robert M. , Holladay Steven D.
Published: October 2007

TCDD and DES have immunotoxic effects, including selective diminution of T lymphocyte progenitors in the fetal liver. The histologic presentation of fetal liver after exposure to either chemical has not been described. Similarly, limited information exists regarding mechanisms by which TCDD or DES may alter fetal hematopoiesis. Treatment of pregnant C57BL/6 mice with either 10 μg/kg/day TCDD or 48 μg/kg/day DES on gestation days (gd) 14 and 16 led to increased fetal liver weight on gd 18. Moderate anisocytosis and anisokaryosis with increased cytoplasmic and nuclear sizes, and increased cytoplasmic basophilia were present within hepatocytes after TCDD or DES. Both chemicals also decreased the presence of hematopoietic cells, however megakaryocyte numbers were unaffected. In contrast to these similar outcomes, real time quantitative PCR using a preliminary panel of 4 genes suggested that the chemicals act through different gene targets. TCDD increased c-jun gene expression in fetal liver, and decreased p53 without alteration in bcl-2 expression, indicating possible pro-proliferative and antiapoptotic effects. DES decreased c-jun and bcl-2, without altering p53, suggesting a shift away from proliferation. Both agents decreased PKC α expression, which may suggest shared decreased phosphorylation of substrates required for normal cell cycle progression.
Role of Neutrophils in the Pathogenesis of Acute Inflammatory Liver Injury
Authors: Ramaiah Shashi K. , Jaeschke Hartmut
Published: October 2007

Polymorphonuclear leukocytes (neutrophils) are essential in the defense against invading microorganisms, tissue trauma or any inciting inflammatory signals. Hepatic infiltration of neutrophils is an acute response to recent or ongoing liver injury, hepatic stress or unknown systemic inflammatory signals. Once neutrophils reach the liver, they can cause mild-to-severe tissue damage and consequent liver failure. For neutrophils to appear in the liver, neutrophils have to undergo systemic activation (priming) by inflammatory mediators such as cytokines, chemokines, complement factors, immune complexes, opsonized particles and other biologically active molecules, e.g., platelet activating factor. Neutrophils accumulated in the hepatic microvasculature (sinusoids and postsinusoidal venules) can extravasate (transmigrate) into the hepatic parenchyma if they receive a signal from distressed cells. Transmigration can be mediated by a chemokine gradient established towards the hepatic parenchyma and generally involves orchestration by adhesion molecules on neutrophils (β2integrins) and on endothelial cells (intracellular adhesion molecules, ICAM-1). After transmigration, neutrophils adhere to distressed hepatocytes through their β2integrins and ICAM-1 expressed on hepatocytes. Neutrophil contact with hepatocytes mediate oxidative killing of hepatocytes by initiation of respiratory burst and neutrophil degranulation leading to hepatocellular oncotic necrosis. Neutrophil-mediated liver injury has been demonstrated in a variety of diseases and chemical/drug toxicities. Relevant examples are discussed in this review.
Chronic Phenobarbital-Induced Mitochondrial Pleomorphism in the Rat Liver
Authors: Almsherqi Zakaria , Mclachlan Craig Steven , Tay Stacey K. H. , Deng Yuru
Published: October 2007

Posttreatment effects of phenobarbital (30 mg/kg I.P. per day for 5 days) on liver mitochondrial TEM ultra-structure in adult rats were studied. Liver mitochondria population samples in treated rats exhibited pleomorphic morphological dumbbell shapes (7%), U-type (crescent) shapes (4%) and O-type (ring-like) shapes (4%). This pathology was not observed in vehicle-treated animals. Phenobarbital is a drug that induces within the rat liver increased protein synthesis in the mitochondria and mitochondrial morphological shape changes.
Novel Insights into Wound Healing Sequence of Events
Authors: Braiman-Wiksman Liora , Solomonik Inessa , Spira Ram , Tennenbaum Tamar
Published: October 2007

Effective wound healing leads to restoration of tissue integrity and occurs through a highly organized multistage process involving various cell types. Currently, methods for wound healing assessment lack a structured system for analysis of quantitative parameters. We have established a unique quantitative assessment strategy of wound healing stages based on histological criteria. Distinctive immunohistochemical parameters including re-epithelialization, epidermal differentiation, cell migration, proliferation, inflammatory response as well as dermal closure, matrix distribution, and skin remodelling were identified and followed during the timeline of wound healing progression. Assessment was based on various defined characteristics and each stage-specific parameter was independently quantified for complete wound closure. This analysis allowed a follow-up of wound healing dynamics and identified the contribution of critical and specific parameters to wound healing physiology and pathology. In this review we demonstrate our assessment strategy of crucial wound healing events and introduce a unique quantification system for each of the processes involved in wound repair. We believe that our unique method can be utilized as a diagnostic platform for standardizing assessment of wound healing progression as well as a screening tool for potential therapies.
Ultraviolet Radiation-Induced Corneal Degeneration in 129 Mice
Authors: Newkirk Kimberly M. , Chandler Heather L. , Parent Allison E. , Young Donn C. , Colitz Carmen M. H. , Wilkie David A. , Kusewitt Donna F.
Published: October 2007

Ultraviolet radiation (UVR) is a risk factor for the development of ocular disease in humans, including acute photokeratitis, chronic corneal spheroidal degeneration, and cataract formation. This report describes the ocular lesions seen in 21 mice chronically exposed to UVR as part of a skin carcinogenicity study. All globes were affected to varying degrees. The primary lesion, not previously reported in UVR-exposed mice, was marked loss of keratocytes relative to age-matched controls. Secondary lesions included corneal stromal thinning, keratoconus, corneal vascularization and fibrosis, keratitis, globe rupture, and phthisis bulbi. In addition, more than 90% of UVR-exposed and unexposed lenses had evidence of cataract formation; this is the first report of the occurrence of spontaneous cataracts in 129 mice. In a subsequent study, apoptotic cells were identified histologically and by cleaved caspase 3 immunoreactivity in the corneal epithelium and, less commonly, in the corneal stroma after acute UVR exposure. Based on this finding, we propose that the loss of keratocytes observed in the chronic study was due to UVR-induced apoptosis.
Effects of Neonatally Administered Diethylstilbestrol on Induction of Mammary Carcinomas Induced by 7, 12-Dimethylbenz[A]Anthracene in Female Rats
Authors: Ninomiya Kenjiro , Kawaguchi Hiroaki , Souda Masakazu , Taguchi Shuuhei , Funato Mamoru , Umekita Yoshihisa , Yoshida Hiroki
Published: October 2007

Various doses of diethylstilbestrol (DES) were administered to rats once at birth. Thereafter, at 50 days after birth, the rats in all groups were given 10 mg 7, 12-dimethylbenz[a]anthracene (DMBA) and undergone necropsy at 300 days after birth. The incidence of mammary carcinomas (MCs) were 50, 54, 91, 39, 19% at 175 days after birth, and 77, 87, 100, 85, 75% at necropsy in the 0, 0.1, 1, 10, 100 μg groups, respectively. The incidence of rats without corpus luteum were 0, 0, 0, 30, 100% at 50 days after birth, and 0, 40, 53, 93, 100% at necropsy in the 0, 0.1, 1, 10, 100 μg groups, respectively. Observation of the whole mount specimens showed a higher number of terminal end buds (TEBs) in the 1 μg group and a lower number in the 100 μg group compared with the control at 50 days after birth. It suggested that the administration of a relatively low dose (1 μg) of DES during neonatal period may increase TEBs, thus resulting in a stimulatory effect on the initiation of MCs.
Mammary Gland Development in Early Pubertal Female Macaques
Authors: Wood Charles E. , Hester Joy M. , Cline J. Mark
Published: October 2007

Ductal morphogenesis of the mammary gland occurs largely in the early pubertal period under the influence of ovarian sex hormones. In this study we characterized developing ductal structures in breast tissue of 14 female prepubertal or early pubertal rhesus monkeys (average age, 2.6 ± 0.1 years). Serum estradiol concentrations ranged from < 5.0 to 61.2 pg/ml, while progesterone concentrations were low in all animals (< 0.6 ng/ml). No corpora lutea were seen on ovarian histology. The most immature mammary glands contained multilayered ducts frequently ending in distinctive terminal end bud structures. Transitional ducts had variably stratified columnar epithelium, often with prominent rounded myoepithelial cells and loose periductal stroma. Mature ducts had simple cuboidal luminal epithelium, flattened myoepithelium, and associated lobular development, typical of the premenopausal breast. Expression of estrogen receptor alpha was significantly higher in immature ducts compared to mature ducts, while progesterone receptor expression, epithelial proliferation, and cytokeratin expression did not show a relationship to the maturity of the ducts. These findings identify dynamic morphologic changes occurring in the primate breast during early puberty and suggest that estradiol (rather than progesterone) is the predominant hormonal stimulus for early ductal and lobular development.
Toxicity and Biomedical Imaging of Layered Nanohybrids in the Mouse
Authors: Flesken-Nikitin Andrea , Toshkov Illia , Naskar Jishnu , Tyner Katherine M. , Williams Rebecca M. , Zipfel Warren R. , Giannelis Emmanuel P. , Nikitin Alexander Yu.
Published: October 2007

Layered nanohybrids (LNH) are a promising nonviral system allowing controlled drug and DNA delivery. In order to test the toxicity of LNH consisting of a magnesium/aluminum core, mice were subjected to subcutaneous, intraperitoneal, and intravenous injections of these nanoparticles at three doses. Intravenous injections resulted in 8% (1 out of 12) lethality at doses 100 μl and 200 μl of 6.96 × 10−4 M solution, while all mice survived after LNH administration by any other routes. Histopathological alterations were limited to mild localized inflammatory lesions in the lungs and the dermis after intravenous and subcutaneous administration, respectively. LNH labeled with Lucifer Yellow were readily detectable in both locations by fluorescent microscopy. To test their potential for intravital imaging, LNH-Lucifer Yellow were injected into the ovarian bursa and successfully visualized by multiphoton microscopy within the ovarian surface epithelial cells. In similar experiments, the ovary and the ovarian bursa were readily detectable by magnetic resonance imaging after administration of modified LNH, where aluminum was substituted for gadolinium. Taken together, these results demonstrate minimal in vivo toxicity of LNH and illuminate their potential as multifunctional nanoscale particles suitable for combination of intravital biomedical imaging with controlled drug release.
The Use of Toxicokinetic Data in Preclinical Safety Assessment: A Toxicologic Pathologist Perspective
Authors: Ploemen Jan-Peter H. T. M. , Kramer Hester , Krajnc Ernö I. , Martin Iain
Published: October 2007

Collection of toxicokinetic data has become a routine practice during the last 15 years in most general toxicity studies on pharma. It enables the correlation of pathological changes with the plasma concentration of drugs and/or their metabolites. This overview summarizes the use of the toxicokinetic data from the perspective of the toxicologic pathologist.
Ocean acidification disrupts induced defences in the intertidal gastropodLittorina littorea
Authors: Bibby Ruth , Cleall-Harding Polly , Rundle Simon , Widdicombe Steve , Spicer John
Published: October 2007

Carbon dioxide-induced ocean acidification is predicted to have major implications for marine life, but the research focus to date has been on direct effects. We demonstrate that acidified seawater can have indirect biological effects by disrupting the capability of organisms to express induced defences, hence, increasing their vulnerability to predation. The intertidal gastropodLittorina littoreaproduced thicker shells in the presence of predation (crab) cues but this response was disrupted at low seawater pH. This response was accompanied by a marked depression in metabolic rate (hypometabolism) under the joint stress of high predation risk and reduced pH. However, snails in this treatment apparently compensated for a lack of morphological defence, by increasing their avoidance behaviour, which, in turn, could affect their interactions with other organisms. Together, these findings suggest that biological effects from ocean acidification may be complex and extend beyond simple direct effects.
The simulation of stress fibre and focal adhesion development in cells on patterned substrates
Authors: Pathak Amit , Deshpande Vikram S , McMeeking Robert M , Evans Anthony G
Published: October 2007

The remodelling of the cytoskeleton and focal adhesion (FA) distributions for cells on substrates with micro-patterned ligand patches is investigated using a bio-chemo-mechanical model. We investigate the effect of ligand pattern shape on the cytoskeletal arrangements and FA distributions for cells having approximately the same area. The cytoskeleton model accounts for the dynamic rearrangement of the actin/myosin stress fibres. It entails the highly nonlinear interactions between signalling, the kinetics of tension-dependent stress-fibre formation/dissolution and stress-dependent contractility. This model is coupled with another model that governs FA formation and accounts for the mechano-sensitivity of the adhesions from thermodynamic considerations. This coupled modelling scheme is shown to capture a variety of key experimental observations including: (i) the formation of high concentrations of stress fibres and FAs at the periphery of circular and triangular, convex-shaped ligand patterns; (ii) the development of high FA concentrations along the edges of the V-, T-, Y- and U-shaped concave ligand patterns; and (iii) the formation of highly aligned stress fibres along the non-adhered edges of cells on the concave ligand patterns. When appropriately calibrated, the model also accurately predicts the radii of curvature of the non-adhered edges of cells on the concave-shaped ligand patterns.
Relative importance of growth and behaviour to elasmobranch suction-feeding performance over early ontogeny
Authors: Lowry Dayv , Motta Philip J
Published: October 2007

Development of the ability to capture prey is crucial to predator survival. Trends in food-capture performance over early ontogeny were quantified for leopard sharksTriakis semifasciataand whitespotted bamboosharksChiloscyllium plagiosumby measuring suction pressure and flow in front of the mouth during feeding. At any size,C. plagiosumproduce greater subambient pressure and ingest more rounded water parcels. Maximum subambient pressure scaled with negative allometry inT. semifasciataand was accompanied by an increase in the time to reach maximum gape. Despite a similar trend in buccal expansion timing, maximum pressure inC. plagiosumscaled with isometry and was accompanied by an earlier onset of hyoid depression and a positive allometric increase in buccal reserve volume. Growth was the primary factor responsible for developmental trends in both species, with size-independent behavioural changes contributing little to overall performance variability. Ontogenetic dietary shifts are predicted for both species as a consequence of size-dependent changes in performance.Chiloscyllium plagiosumbecomes anatomically and behaviourally canalized towards suction feeding, limiting the effective range of prey capture and possibly necessitating stalking.Triakis semifasciata, by contrast, retains the flexibility to employ both ram and suction and therefore captures more elusive prey with age.
Close-up of mushroom-shaped fibrillar adhesive microstructure: contact element behaviour
Authors: Varenberg M , Gorb S
Published: October 2007

To analyse the performance of mushroom-shaped fibrillar adhesive microstructure, its behaviour was studied during different stages of attachment–loading–detachment cycle. Visualizing the evolutions of real contact area of single microfibres, it is shown that the mushroom-shaped geometry of contact elements promotes fast and simple generation of reliable adhesion. The mushroom-shaped geometry seems to transform fibrillar contact elements into passive suction devices and makes them tolerant to overload, thus enhancing their robustness and stability. These findings may also be extrapolated to biological fibrillar attachment devices sharing the same geometry.
Why should anyone care about computing with anyons?
Authors: Brennen Gavin K , Pachos Jiannis K
Published: October 2007

In this article we present a pedagogical introduction of the main ideas and recent advances in the area of topological quantum computation. We give an overview of the concept of anyons and their exotic statistics, present various models that exhibit topological behaviour and establish their relation to quantum computation. Possible directions for the physical realization of topological systems and the detection of anyonic behaviour are elaborated.
On the relation between the principle of maximum dissipation and inelastic evolution given by dissipation potentials
Authors: Hackl Klaus , Fischer Franz Dieter
Published: October 2007

We study the evolution of systems described by internal variables. After the introduction of thermodynamic forces and fluxes, both the dissipation and dissipation potential are defined. Then, the principle of maximum dissipation (PMD) and a minimum principle for the dissipation potential are developed in a variational formulation. Both principles are related to each other. Several cases are shown where both principles lead to the same evolution equations for the internal variables. However, also counterexamples are reported where such an equivalence is not valid. In this case, an extended PMD can be formulated.
A density functional theory of one- and two-layer freezing in a confined colloid system
Authors: Xu Xinliang , Rice Stuart A
Published: October 2007

We report an analysis of the change in character of the fluid-to-solid transition in a quasi-two-dimensional hard-sphere colloid system as the confining wall separation changes from one to two hard-sphere diameters. Our analysis is based on a study of the bifurcation of solutions of the integral equation for the singlet density, using both direct and pair correlation function representations. Two approximations used in previous bifurcation analyses of freezing are improved in the work reported in this paper. The results of the analysis correctly predict the qualitative change in freezing as a function of the confining wall separation and density, specifically the change from a fluid-to-one-layer hexagonal solid transition to a fluid-to-two-layer square solid transition at a wall separation of 1.6 hard-sphere diameters. The numerical predictions of the theory are in semi-quantitative agreement with simulation data for the density dependence of the liquid–solid transition line for wall separations up to 1.6 hard-sphere diameters.
The role of particle shape on the stress distribution in a sandpile
Authors: Zuriguel I , Mullin T
Published: October 2007

The results of an experimental investigation into the counter-intuitive phenomenon that a local minimum in the normal stress profile is sometimes found under the apex of a sandpile are presented. Specifically, the effects of particle shape on the stress distribution are studied and it is shown that anisotropy of the particles significantly enhances the dip. This amplification is attributed to the mechanical stability induced by boundary alignment of the anisotropic particles. Circular, ellipsoidal and pear-shaped cylinders are used and the stress propagates principally towards the sides of the pile through primary stress chains. Secondary chains are also present and we propose that the relationship between the magnitudes of the ratio of primary to secondary chains is correlated with the size of the dip.
A nonlinear stability analysis for magnetized ferrofluid heated from below
Authors: Sunil  , Mahajan Amit
Published: October 2007

A nonlinear (energy) stability analysis is performed for a magnetized ferrofluid layer heated from below, in the stress-free boundary case. By introducing a suitable generalized energy functional, a rigorous nonlinear stability result is derived for a thermoconvective magnetized ferrofluid. The mathematical emphasis is on how to control the nonlinear terms caused by the magnetic body and inertia forces. It is found that the nonlinear critical stability magnetic thermal Rayleigh number does not coincide with that of the linear instability analysis, and thus indicates that the subcritical instabilities are possible. However, it is noted that, in the case of non-ferrofluid, global nonlinear stability Rayleigh number is exactly the same as that for linear instability. For lower values of magnetic parameters, this coincidence is immediately lost. The effect of magnetic parameter,M3, on subcritical instability region has also been analysed. It is shown that with the increase of magnetic parameter,M3, the subcritical instability region between the two theories decreases quickly. We also demonstrate coupling between the buoyancy and the magnetic forces in the nonlinear energy stability analysis.
Who is in control of the stickleback immune system: interactions between
Schistocephalus solidus
and its specific vertebrate host
Authors: Scharsack Jörn Peter , Koch Kamilla , Hammerschmidt Katrin
Published: October 2007

The cestode
Schistocephalus solidus
is a frequent parasite of three-spined sticklebacks and has a large impact on its host's fitness. Selection pressure should therefore be high on stickleback defence mechanisms, like an efficient immune system, and also on parasite strategies to overcome these. Even though there are indications for manipulation of the immune system of its specific second intermediate host by the cestode, nothing is yet known about the chronology of specific interactions of
S. solidus
with the stickleback immune system. We here expected sticklebacks to first mount an innate immune response directly post-exposure to the parasite to clear the infection at an early stage and after an initial lag phase to upregulate adaptive immunity. Most interestingly, we did not find any upregulation of the specific lymphocyte-mediated immune response. Also, the pattern of activation of the innate immune system did not match our expectations: the proliferation of monocytes followed fluctuating kinetics suggesting that the parasite repeatedly installs a new surface coat not immunogenic to the host. Furthermore, the respiratory burst activity, which has the potential to clear an early
S. solidus
infection, was upregulated very late during infection, when the parasite was too big to be cleared but ready for transmission to its final host. We here suggest that the late activation of the innate immune system interferes with the neuroendocrine system, which mediates reduced predation avoidance behaviour and so facilitates the transmission to the final host.
Climatically driven fluctuations in Southern Ocean ecosystems
Authors: Murphy Eugene J , Trathan Philip N , Watkins Jon L , Reid Keith , Meredith Michael P , Forcada Jaume , Thorpe Sally E , Johnston Nadine M , Rothery Peter
Published: October 2007

Determining how climate fluctuations affect ocean ecosystems requires an understanding of how biological and physical processes interact across a wide range of scales. Here we examine the role of physical and biological processes in generating fluctuations in the ecosystem around South Georgia in the South Atlantic sector of the Southern Ocean. Anomalies in sea surface temperature (SST) in the South Pacific sector of the Southern Ocean have previously been shown to be generated through atmospheric teleconnections with El Niño Southern Oscillation (ENSO)-related processes. These SST anomalies are propagated via the Antarctic Circumpolar Current into the South Atlantic (on time scales of more than 1 year), where ENSO and Southern Annular Mode-related atmospheric processes have a direct influence on short (less than six months) time scales. We find that across the South Atlantic sector, these changes in SST, and related fluctuations in winter sea ice extent, affect the recruitment and dispersal of Antarctic krill. This oceanographically driven variation in krill population dynamics and abundance in turn affects the breeding success of seabird and marine mammal predators that depend on krill as food. Such propagating anomalies, mediated through physical and trophic interactions, are likely to be an important component of variation in ocean ecosystems and affect responses to longer term change. Population models derived on the basis of these oceanic fluctuations indicate that plausible rates of regional warming of 1
o
C over the next 100 years could lead to more than a 95% reduction in the biomass and abundance of krill across the Scotia Sea by the end of the century.
Human selection and the relaxation of legume defences against ineffective rhizobia
Authors: Kiers E. Toby , Hutton Mark G , Denison R. Ford
Published: October 2007

Enforcement mechanisms are thought to be important in maintaining mutualistic cooperation between species. A clear example of an enforcement mechanism is how legumes impose sanctions on rhizobial symbionts that fail to provide sufficient fixed N
2
. However, with domestication and breeding in high-soil-N environments, humans may have altered these natural legume defences and reduced the agricultural benefits of the symbiosis. Using six genotypes of soya beans, representing 60 years of breeding, we show that, as a group, older cultivars were better able to maintain fitness than newer cultivars (seed production) when infected with a mixture of effective and ineffective rhizobial strains. Additionally, we found small differences among cultivars in the ratio of effective : ineffective rhizobia released from their nodules, an indicator of future rhizobial strain fitness. When infected by symbionts varying in quality, legume defences against poor-quality partners have apparently worsened under decades of artificial selection.
Quasi-species evolution in subdivided populations favours maximally deleterious mutations
Authors: O'Fallon Brendan D , Adler Frederick R , Proulx Stephen R
Published: October 2007

Most models of quasi-species evolution predict that populations will evolve to occupy areas of sequence space with the greatest concentration of neutral sequences, thus minimizing the deleterious mutation rate and creating mutationally ‘robust’ genomes. In contrast, empirical studies of the principal model of quasi-species evolution, RNA viruses, suggest that the effects of deleterious mutations are more severe than in similar DNA-based microbes. We demonstrate that populations divided into discrete patches connected by dispersal may favour genotypes where the deleterious effect of non-neutral mutations is maximized. This effect is especially strong in the absence of back mutation and when the amount of time spent in hosts prior to dispersal is intermediate. Our results indicate that RNA viruses that produce acute infections initiated by a small number of virions are expected to evolve fragile genetic architectures when compared with other RNA viruses.
A primary role of developmental instability in sexual selection
Authors: Polak Michal , Taylor Phillip W
Published: October 2007

In evolutionary biology, fluctuating asymmetry (FA) is thought to reveal developmental instability (DI, inability to buffer development against perturbations), but its adaptive and genetic bases are being debated. In other fields, such as human clinical genetics, DI is being assessed as incidence of minor morphological abnormalities (MMAs) and used to predict certain fitness outcomes. Here, for the first time, we combine these complementary measures of DI in sexual selection and quantitative genetic studies of a natural population. Comprehensive multivariate analyses demonstrate that FA and MMAs in a condition-dependent sexual ornament, the maleDrosophila bipectinatasex comb used in courtship, are sole significant targets of selection favouring their reduced expression in New Caledonia. Comb FA and MMAs are positively correlated, confirming that each are linked to a common buffering system. Ornament size and DI (as FA and MMAs) are positively correlated, genetically and phenotypically, contrary to theoretical expectation of negative size-FA scaling under the assumption that FA reveals overall genetic quality. There exists significant additive genetic variance for MMAs, demonstrating their evolutionary potential. Ornament DI in New Caledonia is markedly elevated compared with populations where such selection was not detected, suggesting that the increased population-level DI is capacitating adaptive evolution.
Mountain chickadees discriminate between potential cache pilferers and non-pilferers
Authors: Pravosudov Vladimir V
Published: October 2007

Evolution of complex cognition in animals has been linked to complex social behaviour. One of the costs of sociality is increased competition for food which may be reduced by food caching, but cache theft may undermine the benefits of caching. In birds, sophisticated food-caching-related cognition has been demonstrated only for corvids and attributed to their highly social behaviour. Many non-corvid food-caching species exhibit similar complex social behaviour and here I provide experimental evidence that mountain chickadees (
Poecile gambeli
) adjust their caching strategies depending on social context. Chickadees were allowed to cache seeds in the presence of potential cache pilferer, either conspecific or heterospecific (red-breasted nuthatch,
Sitta canadensis
) and a non-pilferer (dark-eyed junco,
Junco hyemalis
) positioned at the opposite sides of the experimental arena. Available caching sites were either exposed to these observers or hidden from their view while the cacher could always see both observers. Chickadees chose caching sites that were hidden from direct view of the potential pilferers while caching in direct view of the non-pilferers. When no pilferers were present, chickadees made equal use of all available caching substrates and there were no differences in the amount of caching in the presence or absence of pilferers. These results suggest that (i) chickadees may be able to recognize potential cache thieves, both conspecific and heterospecific, and adjust their caching strategies to minimize potential cache pilferage and (ii) chickadees appear to discriminate between caching sites that can or cannot be seen by observers, which may allow them to control visual information available to potential pilferers.
Portage in the UK: recent developments
Authors: Russell F.
Published: October 2007

Background  Portage provides home‐based, early intervention and support to families who have a young child with additional needs. Working in the context of the Every Child Matters agenda, the National Portage Association (NPA) aims to develop inclusive, high‐quality provision. This paper reviews their recent work, presents a summary of the findings of a national survey of Portage and discusses their implications.

Methods  All Portage services known to the NPA and local authorities in England were asked to complete a questionnaire and forward another to families using early years' services to evaluate the support they receive.

Results  The survey identified the extent and gaps in Portage provision and the level of unmet need. Families who contributed said they valued Portage because it helped their child and provided support for the whole family.

Discussion of findings  The survey identified 31 local authorities in England, where Portage is not available. Geographical gaps were most notable in the North East and West Midlands regions. Despite a small increase in the extent of Portage provision, it is estimated that services only meet the needs of a small proportion of families that are eligible. Current work may help overcome geographical gaps through supporting the development of high‐quality Portage services but, in endeavouring to meet the needs of families waiting for Portage, it is important not to diminish the quality of support already provided. Portage aims to provide flexible support for families to respond to their individual needs. Evaluating its effectiveness is problematic because of its complex nature but this survey provided an opportunity for families to share their views at a national level.

Conclusions  Continued development work can help Portage provision become more accessible and one of the options routinely available to families who have a young child with additional needs.
Early support developmental journal for children with visual impairment: the case for a new developmental framework for early intervention
Authors: Dale N. , Salt A.
Published: October 2007

Background  Congenital visual impairment has serious consequences for early development, particularly in those with the most profound impairment. Although there is individual variation, developmental delays and risks, including ‘developmental setback’, are widespread. There is no scientifically robust developmental framework grounded in contemporary theory and scientific knowledge to guide early intervention which may prevent or minimize the risk factors and developmental difficulties. The UK governmental initiative, Early Support, gave the impetus for developing a new developmental framework for babies and young children with visual impairment.

Methods  This paper reports on the scientific literature that underpins the new framework and the limitations of existing intervention materials. The case for focusing on particular vulnerable areas and developing a new developmental framework, the Early Support Developmental Journal for babies and children with severe visual impairment, is presented.

Conclusions  The future direction for service delivery and evaluation is briefly described.
Fire effects on insect herbivores in an oak savanna: the role of light and nutrients
Authors: KAY ADAM D. , SCHADE JOHN D. , OGDAHL MEGAN , WESSERLE ELEONORE O. , HOBBIE SARAH E.
Published: October 2007

Abstract 1. Environmental heterogeneity created by prescribed burning provided the context for testing whether the distribution of an oak specialist (the lace bug, Corythuca arcuata) could be explained by stoichiometric mismatches between herbivore and host plant composition.

2. Field observations showed that lace bug density was seven‐fold higher in frequently burned than in unburned units.

3. Lace bug density did not increase with leaf nutrient concentrations, but was instead associated with higher light levels, higher concentrations of leaf carbon (C), lignin and total phenolics, and lower levels of cellulose. In addition, lace bugs reared on high‐light leaves had higher levels of survivorship than those fed on low‐light leaves.

4. Sampling restricted to full‐sun leaves was used to test whether fire‐related changes in leaf nitrogen (N) and phosphorus (P) concentrations have a secondary influence on lace bug success. This sampling provided only limited evidence for nutrient limitation, as decreases in leaf N and P were associated with an increase in lace bug mass but a decrease in density.

5. It is concluded that burning probably promotes lace bug population growth by increasing canopy openness, light penetration, and the availability of C‐based metabolites, and thus simple stoichoimetric mismatches between herbivores and host plants are not of primary importance in this system.