bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of electric and stress field on structures and quantum conduction of Cu nanowires
Authors: He C. , Qi L. , Zhang W. X. , Pan H.
Published: August 2011

The ballistic transport properties of Cu nanowires under different electric and stress fields are investigated for future application in microelectronics using first-principles density-function theory. Relative to the case with the electric field only, the stability and quantum conduction of both nonhelical and helical atomic strands are enhanced by applying a stress field F. Under V = 1 V/Å, the most excellent quantum conductivity is exhibited at F = 1.5 nN for the nonhelical atomic strands while at F = 2 nN for the helical ones, and the latter is more stable with collapse-resistant F high as 3 nN compared to the former as 2 nN.
Ozone: Unresolved discrepancies for dipole oscillator strength distributions, dipole sums, and van der Waals coefficients
Authors: Kumar Ashok , Thakkar Ajit J.
Published: August 2011

Dipole oscillator strength distributions (DOSDs) for ozone are constructed from experimental photoabsorption cross-sections combined with constraints provided by the Kuhn-Reiche-Thomas sum rule, the high-energy behavior of the dipole-oscillator-strength density, and molar refractivity data. A lack of photoabsorption data in the intermediate energy region from 24 to 524 eV necessitates the use of a mixture rule in that region. For this purpose, a DOSD for O2 is constructed first. The dipole properties for O2 are essentially the same as those obtained in earlier work even though most of the input data is from more recent experiments. A discrepancy is found between the refractivity data and photoabsorption data in the 10–20.6 eV range for ozone. A reliable ozone DOSD of the sort obtained for many other species remains out of reach. However, it is suggested that the true dipole properties of ozone lie between those predicted by two distributions that we present.
Communication: Toward ultrafast, reconfigurable logic in the nanoscale
Authors: Amankona-Diawuo Felix K. , Seideman Tamar
Published: August 2011

We propose and illustrate numerically a class of nanoscale, ultrafast logic gates with the further advantage of reconfigurability. Underlying the operation of the gates and their versatility is the concept of polarization control of the electromagnetic energy propagating via metal nanoparticle arrays. Specifically, a set of different logic gates is shown to obtain from a single metal nanoparticle junction by modification of the polarization properties of the input light sources. Implications and extensions of the gates are discussed.
Anti-Landscapes: Caves and Apophasis in the Christian East
Authors: della Dora Veronica
Published: August 2011

Caves occupy a special place in the Christian East. According to the Byzantine traditions, caves are the spaces where biblical paradoxical wonders took place, beyond human vision and understanding (from the birth of Christ from a virgin to his resurrection and the revelation to Saint John on Patmos). In the 4th century biblical caves were officially put on the map of empire by Constantine as sites physically marking the inexplicable dogmas of the newly sanctioned creed. As such they came to constitute primary pilgrimage destinations. But a number of other caves were being populated by increasing numbers of hermits who found in them privileged physical settings for ascetic struggle—for ‘emptying’ themselves of passions and earthly cares in order to be filled by divine grace. Defined by ‘lack of’ matter, light, and comfort, ascetic caves were ‘anti-landscapes’, powerful metaphorical spaces charged with scriptural narratives linked to the apophatic doctrine's via negativa, the encounter with God beyond image, language, and understanding. Finally, caves were also those of the human soul: profundities that took ascetics an entire life to penetrate. This paper explores the physical and imaginative complexities of these anti-landscapes, in which sight is overruled by other senses and conceptual thinking by precognition.
A comparison of population differentiation in two shore crab species with contrasting distribution along the Portuguese coast, using two morphological methodologies
Authors: Silva Inês C. , Hawkins Stephen J. , Paula José
Published: August 2011

Along the Portuguese coast, Pachygrapsus marmoratus has a continuous distribution on rocky shores. In contrast, Carcinus maenas has a discontinuous distribution, inhabiting estuaries. Surveys along a coastal latitudinal gradient were made to assess the effect of the distribution pattern on population differentiation of these two species. Population differentiation was studied using two different morphometric methodologies: linear-based morphometrics and landmark-based morphometrics. The linear-based analysis revealed no significant morphological differentiation among the eleven P. marmoratus populations. Landmark-based analysis showed that the northern and central populations were more similar in shape than the southern populations. Nevertheless, there was still some overlap in shape that could be due to the continuous distribution of P. marmoratus along the coast, promoting population panmixia. In C. maenas, both morphometric techniques revealed the existence of morphological differentiation among populations. This shape differentiation showed a clinal variation, explained by a higher degree of isolation of populations that might be due to limited larval flow between them. Environmental factors may also play an important role in causing variation of shape. Landmark-based morphometrics yielded stronger evidence of morphological differences among forms than a linear approach, suggesting that this method may be more suitable for analysis of body shape.
Reducing impacts of trawling on protected sea snakes: by-catch reduction devices improve escapement and survival
Authors: Milton David A. , Fry Gary C. , Dell Quinton
Published: August 2011

Sea snakes (Hydrophidae) are by-catch of prawn trawling throughout the tropical Indo-western Pacific. We tested the effectiveness of three by-catch reduction device (BRD) types set at different distances from the codend in Australia’s Northern Prawn Fishery (NPF). Trained crew-member observers compared the numbers of sea snakes caught in paired Control and Treatment nets in 1365 trawls. Catches of sea snakes were reduced by 43% on those vessels where a Fisheye BRD was positioned less than 70 meshes from the codend. A separate study with a scientific observer undertook trials with a ‘popeye’ Fishbox BRD. This BRD reduced sea snake catch by 85% and small fish by-catch by 48%. Catches of target prawn were similar for all nets in both studies (difference <2%). Adoption of the more effective BRDs (‘popeye’ Fishbox or Fisheye BRDs) by the NPF and locating them within 70 meshes of the codend can potentially reduce sea snake catch and thus their mortality from ~7000 in the 2007 fishing season to as few as 1500 snakes. Our study shows that the use of BRDs in tropical coastal demersal fisheries and positioning them closer to the codend will greatly reduce the catch of vulnerable sea snakes.
Spatial and temporal variation in lipid and fatty acid profiles of western rock lobster pueruli at first settlement: biochemical indicators of diet and nutritional status
Authors: Limbourn A. J. , Babcock R. C. , Johnston D. J. , Nichols P. D. , Knott B.
Published: August 2011

Rock lobster species are found worldwide and have a life history that includes development through a planktonic phyllosoma followed by a nektonic non-feeding puerulus that relies on stored energy during recruitment into near-shore habitats. Recruitment to adult populations of western rock lobster (Panulirus cygnus) is highly variable and is likely to be strongly influenced by shelf width and oceanic conditions affecting cross-shelf transport and nutrition. Since the nutritional status of newly settled pueruli will reflect the phyllosoma feeding environment and distance swum, we studied levels of lipid, fatty acid (FA) and protein of 422 pueruli and 79 first instar juveniles from four Western Australian locations. Lipid levels generally were inversely related to shelf width but were variable, suggesting pueruli may travel complex trajectories to coastal settlement. Lipid and FA composition of pueruli were consistent with spatial and seasonal variation in Leeuwin Current and coastal productivity regimes. Seasonal differences in FA composition occurred regardless of the year of settlement. Pueruli had lower lipid levels during ENSO years, when recruitment tends to be lower also. Measures of puerulus nutritional status appear to provide valuable insights into the processes underpinning recruitment in Panulirus cygnus and other commercially and ecologically important species.
Dispersal and gene flow in the habitat-forming kelp, Ecklonia radiata: relative degrees of isolation across an east - west coastline
Authors: Coleman M. A. , Gillanders B. M. , Connell S. D.
Published: August 2011

Characterising patterns of dispersal and gene flow in habitat-forming organisms is becoming a focal concern for conservation and management strategies as anthropogenic impacts drive change in coastal ecosystems. Here, we use six microsatellite markers to characterise dispersal and gene flow across the South Australian distribution of the habitat-forming kelp Ecklonia radiata. Populations of E. radiata on subtidal reefs in South Australia were highly genetically structured on large (100s of km, FST = 0.211) and small (10s of km, FST = 0.042) spatial scales with the extent of differentiation positively correlated with geographic distances among populations. Neither the presence of oceanic currents nor intervening rocky reef habitats appeared to facilitate widespread gene flow. There was a trend for island populations to be more genetically differentiated from those on the mainland and to have slightly greater levels of heterozygosity than mainland populations. Our results show relatively low dispersal and gene flow suggesting that recovery following kelp loss may be slow. Such information not only provides insights into relative rates of recovery, but may also identify which populations may be best used for propagation and restoration efforts.
Rab22 controls NGF signaling and neurite outgrowth in PC12 cells
Authors: Wang Liang , Liang Zhimin , Li Guangpu
Published: August 2011

Rab22 is a small GTPase that is localized on early endosomes and regulates early endosomal sorting. This study reports that Rab22 promotes nerve growth factor (NGF) signaling-dependent neurite outgrowth and gene expression in PC12 cells by sorting NGF and the activated/phosphorylated receptor (pTrkA) into signaling endosomes to sustain signal transduction in the cell. NGF binding induces the endocytosis of pTrkA into Rab22-containing endosomes. Knockdown of Rab22 via small hairpin RNA (shRNA) blocks NGF-induced pTrkA endocytosis into the endosomes and gene expression (VGF) and neurite outgrowth. Overexpression of human Rab22 can rescue the inhibitory effects of the Rab22 shRNA, suggesting a specific Rab22 function in NGF signal transduction, rather than off-target effects. Furthermore, the Rab22 effector, Rabex-5, is necessary for NGF-induced neurite outgrowth and gene expression, as evidenced by the inhibitory effect of shRNA-mediated knockdown of Rabex-5. Disruption of the Rab22–Rabex-5 interaction via overexpression of the Rab22-binding domain of Rabex-5 in the cell also blocks NGF-induced neurite outgrowth, suggesting a critical role of Rab22–Rabex-5 interaction in the biogenesis of NGF-signaling endosomes to sustain the signal for neurite outgrowth. These data provide the first evidence for an early endosomal Rab GTPase as a positive regulator of NGF signal transduction and cell differentiation.
Retrolinkin cooperates with endophilin A1 to mediate BDNF–TrkB early endocytic trafficking and signaling from early endosomes
Authors: Fu Xiuping , Yang Yanrui , Xu Chenchang , Niu Yang , Chen Tielin , Zhou Qin , Liu Jia-Jia
Published: August 2011

Brain-derived neurotrophic factor (BDNF) binds to its cell surface receptor TrkB to regulate differentiation, development, synaptic plasticity, and functional maintenance of neuronal cells. Binding of BDNF triggers TrkB dimerization and autophosphorylation, which provides docking sites for adaptor proteins to recruit and activate downstream signaling molecules. The molecular mechanisms underlying BDNF–TrkB endocytic trafficking crucial for spatiotemporal control of signaling pathways remain to be elucidated. Here we show that retrolinkin, a transmembrane protein, interacts with endophilin A1 and mediates BDNF-activated TrkB (pTrk) trafficking and signaling in CNS neurons. We find that activated TrkB colocalizes and interacts with the early endosome marker APPL1. Both retrolinkin and endophilin A1 are required for BDNF-induced dendrite development and acute extracellular signal-regulated kinase activation from early endosomes. Suppression of retrolinkin expression not only blocks BDNF-triggered TrkB internalization, but also prevents recruitment of endophilin A1 to pTrk vesicles trafficking through APPL1-positive endosomes. These findings reveal a novel mechanism for BDNF–TrkB to regulate signaling both in time and space through a specific membrane trafficking pathway.
A phosphatase threshold sets the level of Cdk1 activity in early mitosis in budding yeast
Authors: Harvey Stacy L. , Enciso Germán , Dephoure Noah , Gygi Steven P. , Gunawardena Jeremy , Kellogg Douglas R.
Published: August 2011

Entry into mitosis is initiated by synthesis of cyclins, which bind and activate cyclin-dependent kinase 1 (Cdk1). Cyclin synthesis is gradual, yet activation of Cdk1 occurs in a stepwise manner: a low level of Cdk1 activity is initially generated that triggers early mitotic events, which is followed by full activation of Cdk1. Little is known about how stepwise activation of Cdk1 is achieved. A key regulator of Cdk1 is the Wee1 kinase, which phosphorylates and inhibits Cdk1. Wee1 and Cdk1 show mutual regulation: Cdk1 phosphorylates Wee1, which activates Wee1 to inhibit Cdk1. Further phosphorylation events inactivate Wee1. We discovered that a specific form of protein phosphatase 2A (PP2ACdc55) opposes the initial phosphorylation of Wee1 by Cdk1. In vivo analysis, in vitro reconstitution, and mathematical modeling suggest that PP2ACdc55sets a threshold that limits activation of Wee1, thereby allowing a low constant level of Cdk1 activity to escape Wee1 inhibition in early mitosis. These results define a new role for PP2ACdc55and reveal a systems-level mechanism by which dynamically opposed kinase and phosphatase activities can modulate signal strength.
An assessment of seabird–fishery interactions in the Atlantic Ocean
Authors: Tuck G. N. , Phillips R. A. , Small C. , Thomson R. B. , Klaer N. L. , Taylor F. , Wanless R. M. , Arrizabalaga H.
Published: August 2011

Tuck, G. N., Phillips, R. A., Small, C., Thomson, R. B., Klaer, N. L., Taylor, F., Wanless, R. M., and Arrizabalaga, H. 2011. An assessment of seabird–fishery interactions in the Atlantic Ocean. – ICES Journal of Marine Science, 68: 1628–1637. Currently, 17 of 22 albatross species are listed as Vulnerable, Endangered, or Critically endangered by the International Union for the Conservation of Nature (IUCN). Incidental mortality in fisheries is by far the most widespread cause of the population declines observed for these and other closely related species. In 2006, the International Commission for the Conservation of Atlantic Tunas (ICCAT) requested an assessment of the threat from their fisheries to all seabirds that breed or forage within their jurisdiction. Methods were developed to assess the potential consequences of fishing for more than 60 populations of seabird. The assessment framework involved the identification of at-risk populations, overlap analyses, estimation of total bycatch, and an evaluation of the impact of the bycatch on key selected populations for which there were sufficient data on bird distribution and demography. These were the wandering and black-browed albatrosses of South Georgia and the Atlantic yellow-nosed and Tristan albatrosses of Gough Island. Summary results from the seabird assessment are presented, revealing that ICCAT longline fisheries catch substantial numbers of seabirds, with potentially significant conservation implications. If this mortality is not reduced, the numbers of breeding birds in some populations will continue to decline, threatening their long-term viability.
Multiyear variability of phytoplankton abundance in the Gulf of Maine
Authors: Kane Joseph
Published: August 2011

Kane, J. 2011. Multiyear variability of phytoplankton abundance in the Gulf of Maine. – ICES Journal of Marine Science, 68: 1833–1841. Significant interannual changes in phytoplankton abundance were identified in the Continuous Plankton Recorder time-series collected in the Gulf of Maine from 1961 to 2008. Abundance levels of nearly all the common taxa began to increase in 1990 and remained elevated through 2001. During that period, total numbers were above average throughout the year, with an unusual bloom in late summer. Multivariate analysis of abundance identified three consecutive multiyear periods of varying abundance levels: low to average from 1961 to 1989, above average or very high from 1990 to 2001, and below average thereafter, through 2008. Phytoplankton abundance patterns were closely aligned to the rising trends displayed by several of the common zooplankton taxa. The North Atlantic Oscillation was the only environmental variable examined that showed some association with time-series abundance trends of plankton. The index was primarily positive in the 1990s, which would favour the propagation of warm, nutrient-rich slope water into the region. Perhaps the increased influx of this water, along with feedback enrichment from abundant zooplankton stocks and reduced top-down control by the relative scarcity of the dominant copepod Calanus finmarchicus, combined with a low salinity to make the 1990s a unique decade for plankton change in the Gulf of Maine.
Do big boats tow big nets?
Authors: Reid D. G. , Graham N. , Rihan D. J. , Kelly E. , Gatt I. R. , Griffin F. , Gerritsen H. D. , Kynoch R. J.
Published: August 2011

Reid, D. G., Graham, N., Rihan, D. J., Kelly, E., Gatt, I. R., Griffin, F., Gerritsen, H. D., and Kynoch, R. J. 2011. Do big boats tow big nets? – ICES Journal of Marine Science, 68: 1663–1669. Fishing vessel capacity for trawlers is generally expressed in terms of length, tonnage, and engine power, assuming that a larger vessel has a greater fishing power. Management uses effort-control measures such as kW-day limits based on this assumption. Many studies have shown a weak and noisy relationship between effort and modelled catches, and explanatory models often require the inclusion of a skipper or vessel effect to explain the variance. A key element in this effect is the choice of gear size. Relationships are investigated between metrics of the vessel (length, tonnage, and power) and the gear towed (length of groundgear, or circumference of the net opening) in Scottish and Irish whitefish, Nephrops, and pelagic otter trawlers. Often, the vessel size did not correlate with that of the gear, or did so only for smaller vessels (<1000 hp). The key implication is that effort management based on vessel metrics alone is not appropriate, because it is a poor predictor for gear size, and hence for fishing power. Effort restrictions may actually encourage the adoption of larger gears for a given vessel, to maximize the value of a limited-time resource.
Observations of discards in the Scottish mixed demersal trawl fishery
Authors: Fernandes Paul G. , Coull Kenny , Davis Craig , Clark Peter , Catarino Rui , Bailey Nick , Fryer Rob , Pout Alastair
Published: August 2011

Fernandes, P. G., Coull, K., Davis, C., Clark, P., Catarino, R., Bailey, N., Fryer, R., and Pout, A. 2011. Observations of discards in the Scottish mixed demersal trawl fishery. – ICES Journal of Marine Science, 68: 1734–1742. The Marine Laboratory in Aberdeen (now part of Marine Scotland Science) has operated a scientific observer programme in the Scottish mixed demersal trawl fishery for more than 20 years. Discards of the main demersal species (cod, haddock, whiting, and saithe) have been sampled according to a stratified design based on gear, area, and month, with quota sampling used to select vessels. The aim of the programme is to estimate the quantity (at age) of the discarded component of the catch, to contribute to estimates of total catch for these species so that assessments of each stock can be made. Trends of discards from this observer programme from 1987 to 2009 are reported. Notable features include the sudden practice of discarding marketable cod in 2007. This was due to a number of factors including, paradoxically, improvements in compliance measures which meant that fish could no longer be landed illegally. Methods for raising the sampled discards to the level of the fleet are also explored and discussed in relation to changes in discarding patterns. These are particularly relevant at a time when, in northern Europe at least, there is a move towards standardizing methods for estimating total quantities of discards.
Morphogenesis of an extended phenotype: four-dimensional ant nest architecture
Authors: Minter Nicholas J. , Franks Nigel R. , Robson Brown Katharine A.
Published: August 2011

Animals produce a variety of structures to modify their environments adaptively. Such structures represent extended phenotypes whose development is rarely studied. To begin to rectify this, we used micro-computed tomography (CT) scanning and time-series experiments to obtain the first high-resolution dataset on the four-dimensional growth of ant nests. We show that extrinsic features within the environment, such as the presence of planes between layers of sediment, influence the architecture of
Lasius flavus
nests, with ants excavating horizontal tunnels along such planes. Intrinsically, the dimensions of the tunnels are associated with individual colonies, the dynamics of excavation can be explained by negative feedback and the angular distribution of tunnels is probably a result of local competition among tunnels for miners. The architecture and dynamics of ant nest excavation therefore result from local interactions of ants with one another and templates inherent in the environment. The influence of the environment on the form of structures has been documented across both biotic and abiotic domains. Our study opens up the utility of CT scanning as a technique for observing the morphogenesis of such structures.
Bone–titanium oxide interface in humans revealed by transmission electron microscopy and electron tomography
Authors: Palmquist Anders , Grandfield Kathryn , Norlindh Birgitta , Mattsson Torsten , Brånemark Rickard , Thomsen Peter
Published: August 2011

Osseointegration, the direct contact between an implant surface and bone tissue, plays a critical role in interfacial stability and implant success. Analysis of interfacial zones at the micro- and nano-levels is essential to determine the extent of osseointegration. In this paper, a series of state-of-the-art microscopy techniques are used on laser-modified implants retrieved from humans. Partially laser-modified implants were retrieved after two and a half months' healing and processed for light and electron microscopy. Light microscopy showed osseointegration, with bone tissue growing both towards and away from the implant surface. Transmission electron microscopy revealed an intimate contact between mineralized bone and the laser-modified surface, including bone growth into the nano-structured oxide. This novel observation was verified by three-dimensional Z-contrast electron tomography, enabling visualization of an apatite layer, with different crystal direction compared with the apatite in the bone tissue, encompassing the nano-structured oxide. In conclusion, the present study demonstrates the nano-scale osseointegration and bonding between apatite and surface-textured titanium oxide. These observations provide novel data in human specimens on the ultrastructure of the titanium–bone interface.
Resistance and relatedness on an evolutionary graph
Authors: Maciejewski Wes
Published: August 2011

When investigating evolution in structured populations, it is often convenient to consider the population as an evolutionary graph—individuals as nodes, and whom they may act with as edges. There has, in recent years, been a surge of interest in evolutionary graphs, especially in the study of the evolution of social behaviours. An inclusive fitness framework is best suited for this type of study. A central requirement for an inclusive fitness analysis is an expression for the genetic similarity between individuals residing on the graph. This has been a major hindrance for work in this area as highly technical mathematics are often required. Here, I derive a result that links genetic relatedness between haploid individuals on an evolutionary graph to the resistance between vertices on a corresponding electrical network. An example that demonstrates the potential computational advantage of this result over contemporary approaches is provided. This result offers more, however, to the study of population genetics than strictly computationally efficient methods. By establishing a link between gene transfer and electric circuit theory, conceptualizations of the latter can enhance understanding of the former.
Evolutionary relationship of the L- and M-class genome segments of bat-borne fusogenic orthoreoviruses in Malaysia and Australia
Authors: Voon Kenny , Chua Kaw Bing , Yu Meng , Crameri Gary , Barr Jennifer A. , Malik Yasmin , Wang Lin-Fa
Published: August 2011

We previously described three new Malaysian orthoreoviruses designated Pulau virus, Melaka virus and Kampar virus. Melaka and Kampar viruses were shown to cause respiratory disease in humans. These viruses, together with Nelson Bay virus, isolated from Australian bats, are tentatively classified as different strains within the species Pteropine orthoreovirus (PRV), formerly known as Nelson Bay orthoreovirus, based on the small (S) genome segments. Here we report the sequences of the large (L) and medium (M) segments, thus completing the whole-genome characterization of the four PRVs. All L and M segments were highly conserved in size and sequence. Conserved functional motifs previously identified in other orthoreovirus gene products were also found in the deduced proteins encoded by the cognate segments of these viruses. Detailed sequence analysis identified two genetic lineages divided into the Australian and Malaysian PRVs, and potential genetic reassortment among the M and S segments of the three Malaysian viruses.
RNAi-independent role for Argonaute2 in CTCF/CP190 chromatin insulator function
Authors: Moshkovich Nellie , Nisha Parul , Boyle Patrick J. , Thompson Brandi A. , Dale Ryan K. , Lei Elissa P.
Published: August 2011

A major role of the RNAi pathway in Schizosaccharomyces pombe is to nucleate heterochromatin, but it remains unclear whether this mechanism is conserved. To address this question in Drosophila, we performed genome-wide localization of Argonaute2 (AGO2) by chromatin immunoprecipitation (ChIP)-seq in two different embryonic cell lines and found that AGO2 localizes to euchromatin but not heterochromatin. This localization pattern is further supported by immunofluorescence staining of polytene chromosomes and cell lines, and these studies also indicate that a substantial fraction of AGO2 resides in the nucleus. Intriguingly, AGO2 colocalizes extensively with CTCF/CP190 chromatin insulators but not with genomic regions corresponding to endogenous siRNA production. Moreover, AGO2, but not its catalytic activity or Dicer-2, is required for CTCF/CP190-dependent Fab-8 insulator function. AGO2 interacts physically with CTCF and CP190, and depletion of either CTCF or CP190 results in genome-wide loss of AGO2 chromatin association. Finally, mutation of CTCF, CP190, or AGO2 leads to reduction of chromosomal looping interactions, thereby altering gene expression. We propose that RNAi-independent recruitment of AGO2 to chromatin by insulator proteins promotes the definition of transcriptional domains throughout the genome.
Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation
Authors: Grassian Alexandra R. , Metallo Christian M. , Coloff Jonathan L. , Stephanopoulos Gregory , Brugge Joan S.
Published: August 2011

Loss of extracellular matrix (ECM) attachment leads to metabolic impairments that limit cellular energy production. Characterization of the metabolic alterations induced by ECM detachment revealed a dramatic decrease in uptake of glucose, glutamine, and pyruvate, and a consequent decrease in flux through glycolysis, the pentose phosphate pathway, and the tricarboxylic acid (TCA) cycle. However, flux through pyruvate dehydrogenase (PDH) is disproportionally decreased, concomitant with increased expression of the PDH inhibitory kinase, PDH kinase 4 (PDK4), and increased carbon secretion. Overexpression of ErbB2 maintains PDH flux by suppressing PDK4 expression in an Erk-dependent manner, and Erk signaling also regulates PDH flux in ECM-attached cells. Additionally, epidermal growth factor (EGF), a potent inducer of Erk, positively regulates PDH flux through decreased PDK4 expression. Furthermore, overexpression of PDK4 in ECM-detached cells suppresses the ErbB2-mediated rescue of ATP levels, and in attached cells, PDK4 overexpression decreases PDH flux, de novo lipogenesis, and cell proliferation. Mining of microarray data from human tumor data sets revealed that PDK4 mRNA is commonly down-regulated in tumors compared with their tissues of origin. These results identify a novel mechanism by which ECM attachment, growth factors, and oncogenes modulate the metabolic fate of glucose by controlling PDK4 expression and PDH flux to influence proliferation.
Lineage-specific function of the noncoding Tsix RNA for Xist repression and Xi reactivation in mice
Authors: Ohhata Tatsuya , Senner Claire E. , Hemberger Myriam , Wutz Anton
Published: August 2011

The noncoding Tsix RNA is an antisense repressor of Xist and regulates X inactivation in mice. Tsix is essential for preventing the inactivation of the maternally inherited X chromosome in extraembryonic lineages where imprinted X-chromosome inactivation (XCI) occurs. Here we establish an inducible Tsix expression system for investigating Tsix function in development. We show that Tsix has a clear functional window in extraembryonic development. Within this window, Tsix can repress Xist, which is accompanied by DNA methylation of the Xist promoter. As a consequence of Xist repression, reactivation of the inactive X chromosome (Xi) is widely observed. In the parietal endoderm, Tsix represses Xist and causes reactivation of an Xi-linked GFP transgene throughout development, whereas Tsix progressively loses its Xist-repressing function from embryonic day 9.5 (E9.5) onward in trophoblast giant cells and spongiotrophoblast, suggesting that Tsix function depends on a lineage-specific environment. Our data also demonstrate that the maintenance of imprinted XCI requires Xist expression in specific extraembryonic tissues throughout development. This finding shows that reversible XCI is not exclusive to pluripotent cells, and that in some lineages cell differentiation is not accompanied by a stabilization of the Xi.
Phytoplasma Effector SAP54 Induces Indeterminate Leaf-Like Flower Development in Arabidopsis Plants
Authors: MacLean Allyson M. , Sugio Akiko , Makarova Olga V. , Findlay Kim C. , Grieve Victoria M. , Tóth Réka , Nicolaisen Mogens , Hogenhout Saskia A.
Published: August 2011

Phytoplasmas are insect-transmitted bacterial plant pathogens that cause considerable damage to a diverse range of agricultural crops globally. Symptoms induced in infected plants suggest that these phytopathogens may modulate developmental processes within the plant host. We report herein that Aster Yellows phytoplasma strain Witches’ Broom (AY-WB) readily infects the model plant Arabidopsis (Arabidopsis thaliana) ecotype Columbia, inducing symptoms that are characteristic of phytoplasma infection, such as the production of green leaf-like flowers (virescence and phyllody) and increased formation of stems and branches (witches’ broom). We found that the majority of genes encoding secreted AY-WB proteins (SAPs), which are candidate effector proteins, are expressed in Arabidopsis and the AY-WB insect vector Macrosteles quadrilineatus (Hemiptera; Cicadellidae). To identify which of these effector proteins induce symptoms of phyllody and virescence, we individually expressed the effector genes in Arabidopsis. From this screen, we have identified a novel AY-WB effector protein, SAP54, that alters floral development, resulting in the production of leaf-like flowers that are similar to those produced by plants infected with this phytoplasma. This study offers novel insight into the effector profile of an insect-transmitted plant pathogen and reports to our knowledge the first example of a microbial pathogen effector protein that targets flower development in a host.
Relationship between personality change and the onset and course of alcohol dependence in young adulthood
Authors: Hicks Brian M. , Durbin C. Emily , Blonigen Daniel M. , Iacono William G. , McGue Matt
Published: August 2011

Aims  To examine the reciprocal effects between the onset and course of alcohol use disorder (AUD) and normative changes in personality traits of behavioral disinhibition and negative emotionality during the transition between adolescence and young adulthood.

Design  Longitudinal–epidemiological study assessing AUD and personality at ages 17 and 24 years.

Setting  Participants were recruited from the community and took part in a day‐long, in‐person assessment.

Participants  Male (n = 1161) and female (n = 1022) twins participating in the Minnesota Twin Family Study.

Measurements  The effects of onset (adolescent versus young adult) and course (persistent versus desistent) of AUD on change in personality traits of behavioral disinhibition and negative emotionality from ages 17 to 24 years.

Findings  Onset and course of AUD moderated personality change from ages 17 to 24 years. Adolescent onset AUD was associated with greater decreases in behavioral disinhibition. Those with an adolescent onset and persistent course failed to exhibit normative declines in negative emotionality. Desistence was associated with a ‘recovery’ towards psychological maturity in young adulthood, while persistence was associated with continued personality dysfunction. Personality traits at age 11 predicted onset and course of AUD, indicating personality differences were not due to active substance abuse.

Conclusions  Personality differences present prior to initiation of alcohol use increase risk for alcohol use disorder, but the course of alcohol use disorder affects the rate of personality change during emerging adulthood. Examining the reciprocal effects of personality and alcohol use disorder within a developmental context is necessary to improve understanding for theory and intervention.
Examining the predictive validity of low‐risk gambling limits with longitudinal data
Authors: Currie Shawn R. , Hodgins David C. , Casey David M. , el‐Guebaly Nady , Smith Garry J. , Williams Robert J. , Schopflocher Don P. , Wood Robert T.
Published: August 2011

Aims  To assess the impact of gambling above the low‐risk gambling limits developed by Currie et al. (2006) on future harm. To identify demographic, behavioural, clinical and environmental factors that predict the shift from low‐ to high‐risk gambling habits over time.

Design  Longitudinal cohort study of gambling habits in community‐dwelling adults.

Setting  Alberta, Canada.

Participants  A total of 809 adult gamblers who completed the time 1 and time 2 assessments separated by a 14‐month interval.

Measurements  Low‐risk gambling limits were defined as gambling no more than three times per month, spending no more than CAN$1000 per year on gambling and spending less than 1% of gross income on gambling. Gambling habits, harm from gambling and gambler characteristics were assessed by the Canadian Problem Gambling Index. Ancillary measures of substance abuse, gambling environment, major depression, impulsivity and personality traits assessed the influence of other risk factors on the escalation of gambling intensity.

Findings  Gamblers classified as low risk at time 1 and shifted into high‐risk gambling by time 2 were two to three times more likely to experience harm compared to gamblers who remained low risk at both assessments. Factors associated with the shift from low‐ to high‐risk gambling behaviour from time 1 to time 2 included male gender, tobacco use, older age, having less education, having friends who gamble and playing electronic gaming machines.

Conclusions  An increase in the intensity of gambling behaviour is associated with greater likelihood of future gambling related harm in adults.
Cannabis use and subclinical positive psychotic experiences in early adolescence: findings from a Dutch survey
Authors: van Gastel Willemijn A. , Wigman Johanna T. W. , Monshouwer Karin , Kahn René S. , van Os Jim , Boks Marco P. M. , Vollebergh Wilma A. M.
Published: August 2011

Aims  To investigate the association between early cannabis use and subclinical psychotic experiences, distinguishing between five levels of use: never used, discontinued use (life‐time users who did not use in the preceding year), experimental use, regular use and heavy use.

Design  Cross‐sectional observational study.

Setting  Dutch Health Behaviour in School‐aged Children (HBSC) study, 2005 wave.

Participants  A total of 4552 secondary school children aged 12–16 years.

Measurements  Cannabis use, Community Assessment of Psychic Experiences (CAPE) positive scale, confounding factors: age, gender, family affluence, household composition, social support, alcohol use, cigarette smoking, ethnicity and urbanicity.

Findings  The association between cannabis use and subclinical positive symptoms was confirmed, and remained significant after extensive adjustment for potential confounders. Associations were found for all user groups, with strongest associations for the discontinued use group (β = 0.061, P = 0.000) and for the heavy use group (β = 0.065, P = 0.000).

Conclusions  There is an enduring association between cannabis use at an early age and subclinical positive psychotic experiences, even after abstaining from cannabis for at least 1 year.
Clofarabine with high dose cytarabine and granulocyte colony‐stimulating factor (G‐CSF) priming for relapsed and refractory acute myeloid leukaemia
Authors: Becker Pamela S. , Kantarjian Hagop M. , Appelbaum Frederick R. , Petersdorf Stephen H. , Storer Barry , Pierce Sherry , Shan Jianqin , Hendrie Paul C. , Pagel John M. , Shustov Andrei R. , Stirewalt Derek L. , Faderl Stephan , Harrington Elizabeth , Estey Elihu H.
Published: August 2011

This phase I/II study was conducted to determine the maximum tolerated dose, toxicity, and efficacy of clofarabine in combination with high dose cytarabine and granulocyte colony‐stimulating factor (G‐CSF) priming (GCLAC), in the treatment of patients with relapsed or refractory acute myeloid leukaemia (AML). Dose escalation of clofarabine occurred without dose‐limiting toxicity, so most patients were treated at the maximum dose, 25 mg/m2 per day with cytarabine 2 g/m2 per day, each for 5 d, and G‐CSF 5 μg/kg, beginning the day before chemotherapy and continuing daily until neutrophil recovery. The complete remission (CR) rate among the 46 evaluable patients was 46% (95% confidence interval [CI] 31–61%) and the CR + CR but with a platelet count <100 × 109/l rate was 61% (95% CI 45–75%). Multivariate analysis showed that responses to GCLAC were independent of age, cytogenetic risk category, and number of prior salvage regimens. GCLAC is highly active in relapsed and refractory AML and warrants prospective comparison to other regimens, as well as study in untreated patients.
Individualized toxicity‐titrated 6‐mercaptopurine increments during high‐dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukaemia. A Nordic Society of Paediatric Haematology and Oncology (NOPHO) pilot study
Authors: Frandsen Thomas L. , Abrahamsson Jonas , Lausen Birgitte , Vettenranta Kim , Heyman Mats , Behrentz Michael , Castor Anders , Wehner Peder S. , Frost Britt‐marie , Andersen Elisabeth W. , Schmiegelow Kjeld
Published: August 2011

This study explored the feasibility and toxicity of individualized toxicity‐titrated 6‐mercaptopurine (6MP) dose increments during post‐remission treatment with High‐dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per day if they did not develop myelotoxicity within 2 weeks after HDM. 6MP could be increased in 31 patients (81%). Toxicity was acceptable and did not differ significantly between groups. Patients receiving 75 mg/m2 per day had significantly shorter duration of treatment interruptions of 6MP than the remaining patients (P = 0·03). This study shows individualized toxicity‐titrated 6MP dosing during consolidation is feasible without increased risk of toxicity.
Outcomes of pregnant patients with Pap smears classified as atypical glandular cells
Authors: Slama J. , Freitag P. , Dundr P. , Duskova J. , Fischerova D. , Zikan M. , Pinkavova I. , Cibula D.
Published: August 2011

J. Slama, P. Freitag, P. Dundr, J. Duskova, D. Fischerova, M. Zikan, I. Pinkavova and D. Cibula  Outcomes of pregnant patients with Pap smears classified as atypical glandular cells

Objectives:  The incidence of cervical cancers increases with age. Due to the trend of increasing age of first pregnancy, abnormal Pap smears including those classified as atypical glandular cells (AGC) are being found more often in early pregnancy. Once invasive cancer is excluded, conservative management of squamous intraepithelial lesions (SIL) in pregnancy is considered safe; however, optimal management of AGC is not well established. The aim of our study was to evaluate the outcome of patients with AGC diagnosed from smears during pregnancy.

Methods:  The study included 17 patients referred to us in early pregnancy with Pap smears reported as AGC: 11 not otherwise specified (AGC‐NOS), five favour neoplasia (AGC‐FN) and one adenocarcinoma in situ (AIS). Thirty‐one with high‐grade SIL (HSIL) Pap smears confirmed on punch biopsy in early pregnancy comprised a control group. Human papillomavirus (HPV) positivity was found in seven patients with persistent AGC‐NOS (including all four who had CIN3 postpartum). All the women were initially examined by expert colposcopy and those with AGC‐FN or AIS smears also by transrectal ultrasound to exclude invasive endocervical cancer. Follow‐up controls were carried out every 8–12 weeks and, if there were no signs of progression, revaluation was scheduled 6–8 weeks after delivery.

Results:  The mean age of the women was 31.4 years. Conization in one patient in the study group was performed in the 16th week of pregnancy due to colposcopic signs of microinvasive squamous cell cancer confirmed on histology. Progression to invasive cancer was not found in any of the other 16 patients in the study group or in the control group. Cervical intraepithelial neoplasia or AIS was confirmed postpartum by conization or punch biopsy in 47.1% (8/17) of patients in the study group and, in 77.4% (24/31) of patients in the control group.

Conclusions:  Conservative management of women with AGC in pregnancy is safe where invasive cancer is excluded. As histological verification of glandular pre‐cancerous lesions by punch biopsy is not reliable and the postpartum regression rate cannot be determined precisely, conization should be performed in all cases with AGC‐FN or AIS. Triage of persistent AGC‐NOS with HPV testing is useful in distinguishing significant underlying lesions.
Evidence for hilltopping in bumblebees?
Authors: GOULSON DAVE , SANGSTER ELIZABETH L. , YOUNG JILL C.
Published: August 2011

1. Male bumblebees are known to exhibit a range of mate‐location behaviours, including perching on prominent objects and darting at passing queens, patrolling of scent‐marked flight routes, and waiting outside nest entrances for virgin queens to emerge. Here we provide evidence for a fourth strategy, known as hilltopping. This behaviour is widely known from a range of invertebrates, but has not previously been described in bumblebees.

2. We studied the distribution of bumblebees along transects ascending four hills in Scotland and demonstrate that, relative to workers, males of four bumblebee species or species groups (Bombus lapidarius, B. monticola, B. pascuorum, and B. lucorum/magnus/cryptarum/terrestris) tend to congregate at or near the tops of hills. This is, to our knowledge, the first evidence for hilltopping in bumblebees and the first record of any putative mate‐locating behaviour for male B. pascuorum, a very common species in Europe.

3. We note that, in common with most previous studies of mate‐locating behaviour in bumblebees, attraction of virgin queens and mating were not observed.
Mycorrhiza modulates aboveground tri‐trophic interactions to the fitness benefit of its host plant
Authors: HOFFMANN DANIELA , VIERHEILIG HORST , PENEDER STEFAN , SCHAUSBERGER PETER
Published: August 2011

1. Arbuscular mycorrhiza (AM), the association of AM fungi and plant roots, may alter morphological and physiological attributes of aboveground plant parts and thereby influence plant‐associated organisms such as herbivores and their natural enemies, predators and parasitoids.

2. The interactions between AM and the players of aboveground tri‐trophic systems have mainly been considered in isolation from each other. The effects of AM on aboveground herbivore–carnivore population dynamics and the consequences to plant fitness are unknown.

3. We explored AM‐induced compensatory mechanisms for AM‐promoted proliferation of the herbivorous spider mite, Tetranychus urticae Koch, on whole bean plants, Phaseolus vulgaris L. Vegetative and reproductive plant growth, AM fungal colonisation levels, and mite densities were assessed on spider mite‐infested plants colonised or not by the AM fungus Glomus mosseae Nicol. & Gerd, and harbouring the natural enemy of the spider mites, the predatory mite Phytoseiulus persimilis Anthias‐Henriot or not.

4. AM symbiosis modulated the aboveground tri‐trophic system to the fitness benefit of the plant. AM‐increased plant productivity outweighed the fitness decrease due to AM‐promoted herbivory: at similar vegetative growth, mycorrhizal plants produced more seeds than non‐mycorrhizal plants.

5. AM‐increased spider mite population levels were compensated for by enhanced population growth of the predators and increased plant tolerance to herbivory.

6. AM‐enhanced predator performance looped back to the AM fungus and stabilised its root colonisation levels, providing the first experimental evidence of a mutually beneficial interaction between AM and an aboveground third trophic level natural enemy.