bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanocrystalline diamond films as UV-semitransparent Schottky contacts to 4H-SiC
Authors: Tadjer Marko J. , Hobart Karl D. , Caldwell Joshua D. , Butler James E. , Liu Kendrick X. , Eddy Charles R. , Gaskill D. Kurt , Lew K. K. , VanMil Brenda L. , Myers-Ward Rachael L. , Ancona Mario G. , Kub Fritz J. , Feygelson Tatyana I.
Published: October 2007

A heterojunction between thin films of nanocrystalline diamond (NCD) and 4H-SiC has been developed. Undoped and B-doped NCDs were deposited on both n− and p− SiC epilayers. I-V measurements on p+ NCD∕n− SiC indicated Schottky rectifying behavior with a turn-on voltage of around 0.2V. The current increased over eight orders of magnitude with an ideality factor of 1.17 at 30°C. Ideal energy-band diagrams suggested a possible conduction mechanism for electron transport from the SiC conduction band to either the valence band or acceptor level of the NCD film. Applications as an UV semitransparent electrical contact to 4H-SiC are discussed.
Experimental investigation of bubble formation during capillary filling of SiO2 nanoslits
Authors: Thamdrup Lasse Højlund , Persson Fredrik , Bruus Henrik , Kristensen Anders , Flyvbjerg Henrik
Published: October 2007

Experimental results are presented regarding the influence of bubble formation on the capillary filling speed of water in SiO2 nanoslits with heights ranging from 33to158nm. The formation of an isolated pinned bubble in a nanoslit with a height of 111nm causes an immediate decrease in the filling speed. In nanoslits with heights below 100nm, pinned bubbles are continuously formed at the advancing liquid meniscus. This observed increase in bubble density, which increases the fluidic resistance, quantitatively coincides with an observed reduction of the filling speed during filling of nanoslits with heights below 100nm.
Low-temperature formation of SiO2 layers using a two-step atmospheric pressure plasma-enhanced deposition-oxidation process
Authors: Kakiuchi Hiroaki , Ohmi Hiromasa , Harada Makoto , Watanabe Heiji , Yasutake Kiyoshi
Published: October 2007

Silicon oxide (SiO2) layers were fabricated at low temperatures (⩽400°C) by combining the deposition of hydrogenated amorphous Si (a-Si:H) with its oxidation using atmospheric pressure plasmas excited by a 150MHz very high-frequency (VHF) power. The surface excitation by the atmospheric pressure VHF plasma was capable of reducing the temperature for the hydrogen effusion from a-Si:H. As a result, a porous a-Si:H film containing a large amount of hydrogen could be transformed into a stoichiometric SiO2 with an approximately 24% increase in oxidation rate compared with the oxidation of Si(001) at a temperature of 400°C.
‘Autonomy Online’: Indymedia and Practices of Alter-Globalisation
Authors: Pickerill Jenny
Published: October 2007

The paper examines Australian Indymedia collectives as a means to improve understanding of the practices of alter-globalisation movements. Two key issues are explored. The first concerns the politics of the alter-globalisation movements—what they demand and how they practise their aims. The second concerns the potential of information and communication technologies (ICTs) to provide a space within which to build a radical politics. Several dilemmas facing Indymedia and alter-globalisation movements emerge from this analysis. First, there remain many limitations of using ICTs as a space for the constitution of a radical politics. Second, Indymedia collectives have had success in aligning their aims to their practices; however, informal hierarchies did form around editorial decisions and technical skills. Third, there is continued potential for these movements to appear exclusive. In this respect, simply being ‘open’ is not enough to widen these spaces of resistance. Fourth, there is the continued importance of structure to strengthen the ability of groups to operate non-hierarchically Despite these dilemmas, many of the alter-globalisation movements' practices are proving workable. It is the ability of participants to acknowledge these dilemmas and to continue to be reflexive about their practices that is one of the greatest strengths of these emerging movements.
If You Pick up the Children, I'll Do the Groceries: Spatial Differences in between-Partner Interactions in out-of-Home Household Activities
Authors: Schwanen Tim , Ettema Dick , Timmermans Harry
Published: October 2007

While many studies have been conducted about the allocation of household duties within households, little is known about the impact of land use and accessibility on the distribution of out-of-home household tasks between spouses and about men's participation in such activities. This paper addresses this impact, while controlling for the impact of household structure, life cycle, employment status and hours, access to transport systems, and interactions among activities in persons' activity schedules. Path models for male–female couples in the Amsterdam–Utrecht corridor, the Netherlands, show that land use and accessibility influence between-partner interactions in maintenance activity participation, although their role appears to be smaller than that of sociodemographics and access to transport systems. While women perform the bulk of out-of-home household tasks, men are responsible for a larger share of out-of-home household duties in neighbourhoods characterised by a higher population density and/or more diversity of land uses than they are in lower density and/or less diverse neighbourhoods. However, women's responsibilities are not reduced to the same extent, because spouses' joint participation is also somewhat larger in higher density, more diverse neighbourhoods and because part of men's participation in these neighbourhoods reflects household activities not undertaken elsewhere.
The Spatial Targeting of Urban Policy Initiatives: A Geodemographic Assessment Tool
Authors: Batey Peter , Brown Peter
Published: October 2007

Government frequently adopts an area-based approach to the targeting of urban policy initiatives as an indirect way of reaching the individuals that the initiatives are intended to help. The paper develops a method for assessing the success of this spatial targeting. It uses a geodemographic classification system to produce a generalised socioeconomic profile for a particular initiative. This profile can be used to examine the targeting of the initiative in different localities, in order to assess whether targeting has been inefficient (the targeted areas have been defined so that many of the people they contain are in fact not those for whom the initiative is intended) or incomplete (deserving cases have been missed because the initiative's boundaries have been drawn too tightly). The utility of the method is demonstrated by employing the P2 People and Places geodemographic system to assess the targeting of the Sure Start initiative in eight large provincial cities in England.
Growth and carcass characteristics of cast-for-age Merino ewes fed sorghum-based feedlot diets
Authors: Bowen M. K. , Pepper P. M. , Patterson E. , McConnel I. , Jordan D. J.
Published: October 2007

Grain feeding low bodyweight, cast-for-age (CFA) sheep from pastoral areas of eastern Australia at the end of the growing season can enable critical carcass weight grades to be achieved and thus yield better economic returns. The aim of this work was to compare growth and carcass characteristics for CFA Merino ewes consuming either simple diets based on whole sorghum grain or commercial feed pellets. The experiment also compared various sources of additional nitrogen (N) for inclusion in sorghum diets and evaluated several introductory regimes. Seventeen ewes were killed initially to provide baseline carcass data and the remaining 301 ewes were gradually introduced to the concentrate diets over 14 days before being fed concentrates and wheaten hay ad libitum for 33 or 68 days. Concentrate treatments were: (i) commercial feed pellets, (ii) sorghum mix (SM; whole sorghum grain, limestone, salt and molasses) + urea and ammonium sulfate (SMU), (iii) SMU + whole cottonseed at 286 g/kg of concentrate dry matter (DM), (iv) SM + cottonseed meal at 139 g/kg of concentrate DM, (v) SMU + virginiamycin (20 mg/kg of concentrate) for the first 21 days of feeding, and (vi) whole cottonseed gradually replaced by SMU over the first 14 days of feeding.
The target carcass weight of 18 kg was achieved after only 33 days on feed for the pellets and the SM + cottonseed meal diet. All other whole grain sorghum diets required between 33 and 68 days on feed to achieve the target carcass weight. Concentrates based on whole sorghum grain generally produced significantly (P < 0.05) lower carcass weight and fat score than pellets and this may have been linked to the significantly (P < 0.05) higher faecal starch concentrations for ewes consuming sorghum-based diets (270 v. 72 g/kg DM on day 51 of feeding for sorghum-based diets and pellets, respectively). Source of N in whole grain sorghum rations and special introductory regimes had no significant (P > 0.05) effects on carcass weight or fat score of ewes with the exception of carcass weight for SMU + whole cottonseed being significantly lower than SM + cottonseed meal at day 33.
Ewes finished on all diets produced acceptable carcasses although muscle pH was high in all ewe carcasses (average 5.8 and 5.7 at 33 and 68 days, respectively). There were no significant (P > 0.05) differences between diets in concentrate DM intake, rumen fluid pH, meat colour score, fat colour score, eye muscle area, meat pH or meat temperature.
Application of composted pig bedding litter on a Vertosol and Sodosol soil. 2. Effect on soil chemical and physical fertility
Authors: Armstrong R. D. , Eagle C. , Jarwal S. D.
Published: October 2007

The application of composted bedding litter (wheat straw or rice hulls) that had been used to house swine has been shown to significantly improve the yield and water use of dry land grain crops growing on two contrasting soil types (a Vertosol and Sodosol) in the Wimmera region of Victoria, Australia. The effect of applying this composted litter on a range of chemical and physical properties of these soils was investigated to better understand how the composted bedding litter improved grain production.
Applying bedding litter significantly increased soil total nitrogen (N) and organic carbon in both the Vertosol and Sodosol in the season after application in proportion to the rate of litter application. Applying pig bedding litter also significantly (P < 0.05) increased the level of more labile soil fertility indicators. Soil nitrate (NO3) concentration at the time of sowing of both canola in 1998 (second crop after initial application of litter) and oats/field peas in 1999 (third crop) was significantly higher than control plots at both sites, with values as high as 90 mg NO3/kg soil in the topsoil being recorded. Most of the soil NO3 resulting from the application of bedding litter was concentrated in the topsoil of the poorly structured Sodosol whereas on the Vertosol, soil NO3 tended to be distributed more evenly throughout the soil profile. Litter application also increased soil microbial N concentrations in the topsoil.
Soil physical structure was improved by adding bedding litter, especially on the Sodosol soil. The application of litter decreased the number of small, unstable aggregates (250–1000 µm) whereas the number of large (>2000 µm) water stable aggregates in the topsoil (0–10 cm) was increased. Applying bedding litter also significantly decreased the exchangeable sodium percentage on the Sodosol but not on the Vertosol. Cone penetrometer resistance was reduced in the subsoil at both sites following the application of bedding litter. It was concluded that the beneficial effects of applying pig bedding litter on grain crops was attributed to several factors but the over riding effect appeared due to improved N supply on the well structured Vertosol and enhanced soil structure on the Sodosol.
Symmetries in human brain language pathways correlate with verbal recall
Authors: Catani Marco , Allin Matthew P. G. , Husain Masud , Pugliese Luca , Mesulam Marsel M. , Murray Robin M. , Jones Derek K.
Published: October 2007

Lateralization of language to the left hemisphere is considered a key aspect of human brain organization. We used diffusion tensor MRI to performin vivovirtual dissection of language pathways to assess the relationship between brain asymmetry and cognitive performance in the normal population. Our findings suggest interhemispheric differences in direct connections between Broca's and Wernicke's territories, with extreme leftward lateralization in more than half of the subjects and bilateral symmetrical distribution in only 17.5% of the subjects. Importantly, individuals with more symmetric patterns of connections are better overall at remembering words using semantic association. Moreover, preliminary analysis suggests females are more likely to have a symmetrical pattern of connections. These findings suggest that the degree of lateralization of perisylvian pathways is heterogeneous in the normal population and, paradoxically, bilateral representation, not extreme lateralization, might ultimately be advantageous for specific cognitive functions.
The EGF receptor is required for efficient liver regeneration
Authors: Natarajan Anuradha , Wagner Bettina , Sibilia Maria
Published: October 2007

Mice lacking the EGF receptor (EGFR) die between midgestation and postnatal day 20 with various defects in neural and epithelial organs. Here, we generated mice carrying a floxed
EGFR
allele to inactivate the EGFR in fetal and adult liver. Perinatal deletion of EGFR in hepatocytes resulted in decreased body weight, whereas deletion in the adult liver did not affect body mass. Although liver function was not affected, after partial hepatectomy mice lacking EGFR in the liver showed increased mortality accompanied by increased levels of serum transaminases indicating liver damage. Liver regeneration was delayed in the mutants because of reduced hepatocyte proliferation. Analysis of cell cycle progression in EGFR-deficient livers indicated a defective G
1
–S phase entry with delayed transcriptional activation and reduced protein expression of cyclin D1 followed by reduced cdk2 and cdk1 expression. Impaired liver regeneration was accompanied by compensatory up-regulation of TNFα in the serum and prolonged activation of c-Jun. Moreover, p38α and NF-κB activation was reduced in regenerating mutant livers, indicating an impaired stress response after hepatectomy. Our studies demonstrate that EGFR is a critical regulator of hepatocyte proliferation in the initial phases of liver regeneration.
Negative correlation does not imply a tradeoff between growth and reproduction in California oaks
Authors: Knops Johannes M. H. , Koenig Walter D. , Carmen William J.
Published: October 2007

A tradeoff between growth and reproduction, often inferred from an inverse correlation between these two variables, is a fundamental paradigm of life-history evolution. Oak species provide a unique test of this relationship because different species mature acorns either in the year of pollination or in the year after pollination. This difference allows for an interspecific comparison testing whether the apparent tradeoff is causal or the result of confounding factors influencing growth and reproduction independently. Based on 13 years of data on five California oak species, we found significant negative correlations between radial growth and seed production in the three species that produce acorns the same year in which pollination occurs, but not in two species that mature acorns the year after pollination. Rainfall, which correlates positively with radial growth and correlates negatively with acorn production (based on the year of pollination), appears to be driving this pattern. We conclude that the observed negative correlations are not causal, but rather a consequence of growth and reproduction being dependent, in opposite ways, on environmental conditions. Thus, contrary to the current consensus, growth and reproduction in these species are apparently largely independent of each other. In contrast, tradeoffs between current and future reproduction appear to be much more important in the life-history evolution of these long-lived plants. We also conclude that a negative correlation does not necessarily imply a causal mechanism and should not be used as the only evidence supporting a tradeoff.
Fluctuations in density of an outbreak species drive diversity cascades in food webs
Authors: Eveleigh Eldon S. , McCann Kevin S. , McCarthy Peter C. , Pollock Steven J. , Lucarotti Christopher J. , Morin Benoit , McDougall George A. , Strongman Douglas B. , Huber John T. , Umbanhowar James , Faria Lucas D. B.
Published: October 2007

Patterns in food-web structure have frequently been examined in static food webs, but few studies have attempted to delineate patterns that materialize in food webs under nonequilibrium conditions. Here, using one of nature's classical nonequilibrium systems as the food-web database, we test the major assumptions of recent advances in food-web theory. We show that a complex web of interactions between insect herbivores and their natural enemies displays significant architectural flexibility over a large fluctuation in the natural abundance of the major herbivore, the spruce budworm (Choristoneura fumiferana). Importantly, this flexibility operates precisely in the manner predicted by recent foraging-based food-web theories: higher-order mobile generalists respond rapidly in time and space by converging on areas of increasing prey abundance. This “birdfeeder effect” operates such that increasing budworm densities correspond to a cascade of increasing diversity and food-web complexity. Thus, by integrating foraging theory with food-web ecology and analyzing a long-term, natural data set coupled with manipulative field experiments, we are able to show that food-web structure varies in a predictable manner. Furthermore, both recent food-web theory and longstanding foraging theory suggest that this very same food-web flexibility ought to be a potent stabilizing mechanism. Interestingly, we find that this food-web flexibility tends to be greater in heterogeneous than in homogeneous forest plots. Because our results provide a plausible mechanism for boreal forest effects on populations of forest insect pests, they have implications for forest and pest management practices.
Galactolipid synthesis in chloroplast inner envelope is essential for proper thylakoid biogenesis, photosynthesis, and embryogenesis
Authors: Kobayashi Koichi , Kondo Maki , Fukuda Hiroaki , Nishimura Mikio , Ohta Hiroyuki
Published: October 2007

The biogenesis of thylakoid membranes, an indispensable event for the photoautotrophic growth of plants, requires a significant increase in the level of the unique thylakoid membrane lipid monogalactosyldiacylglycerol (MGDG), which constitutes the bulk of membrane lipids in chloroplasts. The final step in MGDG biosynthesis occurs in the plastid envelope and is catalyzed by MGDG synthase. Here we report the identification and characterization of an
Arabidopsis
mutant showing a complete defect in MGDG synthase 1. The mutant seeds germinated as small albinos only in the presence of sucrose. The seedlings lacked galactolipids and had disrupted photosynthetic membranes, leading to the complete impairment of photosynthetic ability and photoautotrophic growth. Moreover, invagination of the inner envelope, which is not seen in mature WT chloroplasts, was observed in the mutant, supporting an old hypothesis that envelope invagination is a major event in early chloroplast biogenesis. In addition to the defective seedling phenotype, embryo development was arrested in the mutant, although seeds with impaired embryos could germinate heterotrophically. These results demonstrate the importance of galactolipids not only in photosynthetic growth but also in embryogenesis.
Exploring the biochemical properties and remediation applications of the unusual explosive-degrading P450 system XplA/B
Authors: Jackson Rosamond G. , Rylott Elizabeth L. , Fournier Diane , Hawari Jalal , Bruce Neil C.
Published: October 2007

Widespread contamination of land and groundwater has resulted from the use, manufacture, and storage of the military explosive hexa-hydro-1,3,5-trinitro-1,3,5-triazine (RDX). This contamination has led to a requirement for a sustainable, low-cost method to remediate this problem. Here, we present the characterization of an unusual microbial P450 system able to degrade RDX, consisting of flavodoxin reductase XplB and fused flavodoxin-cytochrome P450 XplA. The affinity of XplA for the xenobiotic compound RDX is high (
K
d
= 58 μM) and comparable with the
K
m
of other P450s toward their natural substrates (ranging from 1 to 500 μM). The maximum turnover (
k
cat
) is 4.44 per s, only 10-fold less than the fastest self-sufficient P450 reported, BM3. Interestingly, the presence of oxygen determines the final products of RDX degradation, demonstrating that the degradation chemistry is flexible, but both pathways result in ring cleavage and release of nitrite. Carbon monoxide inhibition is weak and yet the nitroaromatic explosive 2,4,6-trinitrotoluene (TNT) is a potent inhibitor. To test the efficacy of this system for the remediation of groundwater, transgenic
Arabidopsis
plants expressing both
xplA
and
xplB
were generated. They are able to remove saturating levels of RDX from liquid culture and soil leachate at rates significantly faster than those of untransformed plants and
xplA
-only transgenic lines, demonstrating the applicability of this system for the phytoremediation of RDX-contaminated sites.
A comparison of resting-state brain activity in humans and chimpanzees
Authors: Rilling James K. , Barks Sarah K. , Parr Lisa A. , Preuss Todd M. , Faber Tracy L. , Pagnoni Giuseppe , Bremner J. Douglas , Votaw John R.
Published: October 2007

In humans, the wakeful resting condition is characterized by a default mode of brain function involving high levels of activity within a functionally connected network of brain regions. This network has recently been implicated in mental self-projection into the past, the future, or another individual's perspective. Here we use [
18
F]-fluorodeoxyglucose positron emission tomography imaging to assess resting-state brain activity in our closest living relative, the chimpanzee, as a potential window onto their mental world and compare these results with those of a human sample. We find that, like humans, chimpanzees show high levels of activity within default mode areas, including medial prefrontal and medial parietal cortex. Chimpanzees differ from our human sample in showing higher levels of activity in ventromedial prefrontal cortex and lower levels of activity in left-sided cortical areas involved in language and conceptual processing in humans. Our results raise the possibility that the resting state of chimpanzees involves emotionally laden episodic memory retrieval and some level of mental self-projection, albeit in the absence of language and conceptual processing.
Adenosine receptor A
2A
-R contributes to motoneuron survival by transactivating the tyrosine kinase receptor TrkB
Authors: Wiese Stefan , Jablonka Sibylle , Holtmann Bettina , Orel Nadiya , Rajagopal Rithwick , Chao Moses V. , Sendtner Michael
Published: October 2007

Neurotrophins are potent survival factors for developing and injured neurons. However, they are not being used to treat neurodegenerative diseases because of difficulties in administration and numerous side effects that have been encountered in previous clinical trials. Their biological activities use Trk (tropomyosin-related kinase) transmembrane tyrosine kinases. Therefore, one alternative approach is to use transactivation pathways such as adenosine 2A receptor agonists, which can activate Trk receptor signaling independent of neurotrophin binding. However, the relevance
in vivo
and applicability of these transactivation events during neurodegenerative and injury conditions have never been extensively studied. Here we demonstrate that motoneuron survival after facial nerve lesioning is significantly enhanced by transactivation of Trk receptor tyrosine kinases by adenosine agonists. Moreover, survival of motoneurons directly required the activation of the BDNF receptor TrkB and an increase in Akt (AKT8 virus oncogene cellular homolog) activity. The ability of small molecules to activate a trophic response by using Trk signaling provides a unique mechanism to promote survival signals in motoneurons and suggests new strategies for using transactivation in neurodegenerative diseases.
Hepatocyte survival in acute hepatitis is due to c-Jun/AP-1-dependent expression of inducible nitric oxide synthase
Authors: Hasselblatt Peter , Rath Martina , Komnenovic Vukoslav , Zatloukal Kurt , Wagner Erwin F.
Published: October 2007

Analysis of the molecular factors determining hepatocyte survival or death in response to inflammatory stimuli is essential for understanding the pathogenesis of inflammatory liver disease and for identifying novel therapeutic approaches. c-Jun N-terminal kinase (JNK) is a major mediator of cytokine-induced cell death during hepatitis, but the signaling pathways downstream of JNK remain less well defined. Here we show that the transcription factor c-Jun/AP-1, a prototypic target of JNK, is strongly expressed in the liver of patients with acute liver injury. The molecular function of c-Jun in inflammatory liver disease was analyzed in mice by using the Con A model of T cell-mediated hepatitis. Mice lacking c-Jun in hepatocytes display increased liver cell death and mortality upon Con A injection. This phenotype is caused by impaired expression of inducible nitric oxide synthase (
nos2
), a direct transcriptional target of c-Jun, and reduced production of hepatoprotective nitric oxide (NO). Moreover, increased hepatotoxicity in mutant mice is likely caused by hypoxia and oxidative stress and can be rescued pharmacologically by liver-specific NO delivery. These findings demonstrate that c-Jun/AP-1 is hepatoprotective during acute hepatitis by regulating
nos2
/NO expression and thus functionally antagonizes the cell death-promoting functions of JNK.
SIK1 is part of a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process
Authors: Sjöström Mattias , Stenström Karin , Eneling Kristina , Zwiller Jean , Katz Adrian I. , Takemori Hiroshi , Bertorello Alejandro M.
Published: October 2007

In mammalian cells, active sodium transport and its derived functions (e.g., plasma membrane potential) are dictated by the activity of the Na
+
,K
+
-ATPase (NK), whose regulation is essential for maintaining cell volume and composition, as well as other vital cell functions. Here we report the existence of a salt-inducible kinase-1 (SIK1) that associates constitutively with the NK regulatory complex and is responsible for increases in its catalytic activity following small elevations in intracellular sodium concentrations. Increases in intracellular sodium are paralleled by elevations in intracellular calcium through the reversible Na
+
/Ca
2+
exchanger, leading to the activation of SIK1 (Thr-322 phosphorylation) by a calcium calmodulin-dependent kinase. Activation of SIK1 results in the dephosphorylation of the NK α-subunit and an increase in its catalytic activity. A protein phosphatase 2A/phosphatase methylesterase-1 (PME-1) complex, which constitutively associates with the NK α-subunit, is activated by SIK1 through phosphorylation of PME-1 and its dissociation from the complex. These observations illustrate the existence of a distinct intracellular signaling network, with SIK1 at its core, which is triggered by a monovalent cation (Na
+
) and links sodium permeability to its active transport.
Herpes simplex virus-infected cell protein 0 blocks the silencing of viral DNA by dissociating histone deacetylases from the CoREST–REST complex
Authors: Gu Haidong , Roizman Bernard
Published: October 2007

A preeminent phenotype of the infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) is that it acts as a promiscuous transactivator. In most cell lines exposed to ΔICP0 mutant virus at low ratios of virus per cell infection, α genes are expressed but the transition to β and γ gene expression does not ensue, but can be enhanced by inhibitors of histone deacetylases (HDACs). Earlier studies have shown that ICP0 interacts with CoREST and displaces HDAC1 from the CoREST–REST–HDAC1/2 complex. HDAC1 and CoREST are then independently translocated to the cytoplasm. Here, we test the hypothesis that ICP0 blocks the silencing of HSV DNA by displacing HDAC1 from the CoREST–REST complex. Specifically, first, mapping studies led us to construct a truncated CoREST (CoREST
146–482
) that in transfected cells displaced HDAC1 from the CoREST–REST complex. Second, we constructed two viruses. In BACs encoding the entire HSV-1, we replaced the gene encoding ICP0 with AmpR to yield a ΔICP0 mutant R8501. We also replaced ICP0 with CoREST
146–482
to yield recombinant R8502. The yield of R8502 mutant virus in Vero, HEp-2, and human embryonic lung cells exposed to 0.1 pfu of virus per cell was 100-, 10-, and 10-fold higher, respectively, than those of R8501 mutant virus. In Vero cells, the yield of R8502 was identical with that of wild-type virus. We conclude that CoREST
146–482
functionally replaced ICP0 and that, by extension, ICP0 acts to block the silencing of viral DNA by displacing HDAC1/2 from the CoREST–REST complex.
EGF receptor ubiquitination is not necessary for its internalization
Authors: Huang Fangtian , Goh Lai Kuan , Sorkin Alexander
Published: October 2007

Ubiquitination of the EGF receptor (EGFR) has been implicated in EGF-induced receptor internalization, lysosomal degradation, and down-regulation. Mutation of EGFR ubiquitination sites identified by mass spectrometry yielded receptor mutants that are weakly ubiquitinated and not down-regulated by EGF. However, these EGFR mutants were normally internalized. To examine whether this internalization was mediated by the residual ubiquitination, systematic mutagenesis of lysine residues in the kinase domain of the EGFR was performed to generate a receptor mutant that is not ubiquitinated. Mutations of a number of lysines inhibited kinase activity of the EGFR, thus leading to the inhibition of receptor internalization. However, a mutant lacking 15 lysine residues (15KR), which was negligibly ubiquitinated and normally phosphorylated, was internalized at a rate similar to that of the wild-type EGFR. As in the case of the wild-type EGFR, internalization of the 15KR mutant depended on the presence of clathrin, Grb2 adaptor, and Cbl ubiquitin ligase. These data imply that EGFR ubiquitination is not necessary for its internalization by clathrin-coated pits. Interestingly, the reconstitution of two major ubiquitination sites in the 16KR receptor mutant, which had impaired kinase activity and slow internalization kinetics, resulted in a partial rescue of ubiquitination and a complete rescue of receptor internalization. This result suggests that ubiquitination of the kinase-impaired receptor can mediate its internalization by the clathrin pathway. Altogether these data emphasize the robustness of the EGFR internalization process, which can be controlled by multiple kinase- and ubiquitination-dependent and -independent mechanisms.
Dendritic spikes induce single-burst long-term potentiation
Authors: Remy Stefan , Spruston Nelson
Published: October 2007

The hippocampus is essential for episodic memory, which requires single-trial learning. Although long-term potentiation (LTP) of synaptic strength is a candidate mechanism for learning, it is typically induced by using repeated synaptic activation to produce precisely timed, high-frequency, or rhythmic firing. Here we show that hippocampal synapses potentiate robustly in response to strong activation by a single burst. The induction mechanism of this single-burst LTP requires activation of NMDA receptors, L-type voltage-gated calcium channels, and dendritic spikes. Thus, dendritic spikes are a critical trigger for a form of LTP that is consistent with the function of the hippocampus in episodic memory.
Antagonistic pleiotropic effects reduce the potential adaptive value of the FRIGIDA locus
Authors: Scarcelli Nora , Cheverud James M. , Schaal Barbara A. , Kover Paula X.
Published: October 2007

Although the occurrence of epistasis and pleiotropy is widely accepted at the molecular level, its effect on the adaptive value of fitness-related genes is rarely investigated in plants. Knowledge of these features of a gene is critical to understand the molecular basis of adaptive evolution. Here we investigate the importance of pleiotropy and epistasis in determining the adaptive value of a candidate gene using the gene
FRI
(FRIGIDA), which is thought to be the major gene controlling flowering time variation in
Arabidopsis thaliana
. The effect of
FRI
on flowering time was analyzed in an outbred population created by randomly mating 19 natural accessions of
A. thaliana
. This unique population allows the estimation of
FRI
effects independent of any linkage association with other loci due to demographic processes or to coadapted genes. It also allows for the estimation of pleiotropic effects of
FRI
on fitness and inflorescence architecture. We found that
FRI
explains less variation in flowering time than previously observed among natural accessions, and interacts epistatically with the
FLC
locus. Although early flowering plants produce more fruits under spring conditions, and nonfunctional alleles of
FRI
were associated with early flowering, variation at
FRI
was not associated with fitness. We show that nonfunctional
FRI
alleles have negative pleiotropic effects on fitness by reducing the numbers of nodes and branches on the inflorescence. We propose that these antagonistic pleiotropic effects reduce the adaptive value of
FRI
, and helps explain the maintenance of alternative life history strategies across natural populations of
A. thaliana
.
Cyclic changes in metabolic state during the life of a yeast cell
Authors: Tu Benjamin P. , Mohler Rachel E. , Liu Jessica C. , Dombek Kenneth M. , Young Elton T. , Synovec Robert E. , McKnight Steven L.
Published: October 2007

Budding yeast undergo robust oscillations in oxygen consumption during continuous growth in a nutrient-limited environment. Using liquid chromatography-mass spectrometry and comprehensive 2D gas chromatography-mass spectrometry-based metabolite profiling methods, we have determined that the intracellular concentrations of many metabolites change periodically as a function of these metabolic cycles. These results reveal the logic of cellular metabolism during different phases of the life of a yeast cell. They may further indicate that oscillation in the abundance of key metabolites might help control the temporal regulation of cellular processes and the establishment of a cycle. Such oscillations in metabolic state might occur during the course of other biological cycles.
RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling
Authors: Stewart Grant S. , Stankovic Tatjana , Byrd Philip J. , Wechsler Thomas , Miller Edward S. , Huissoon Aarn , Drayson Mark T. , West Stephen C. , Elledge Stephen J. , Taylor A. Malcolm R.
Published: October 2007

Cellular DNA double-strand break-repair pathways have evolved to protect the integrity of the genome from a continual barrage of potentially detrimental insults. Inherited mutations in genes that control this process result in an inability to properly repair DNA damage, ultimately leading to developmental defects and also cancer predisposition. Here, we describe a patient with a previously undescribed syndrome, which we have termed RIDDLE syndrome (radiosensitivity, immunodeficiency, dysmorphic features and learning difficulties), whose cells lack an ability to recruit 53BP1 to sites of DNA double-strand breaks. As a consequence, cells derived from this patient exhibit a hypersensitivity to ionizing radiation, cell cycle checkpoint abnormalities, and impaired end-joining in the recombined switch regions. Sequencing of
TP53BP1
and other genes known to regulate ionizing radiation-induced 53BP1 foci formation in this patient failed to detect any mutations. Therefore, these data indicate the existence of a DNA double-strand break-repair protein that functions upstream of 53BP1 and contributes to the normal development of the human immune system.
N-ethyl-N-nitrosourea (ENU)-Induced Meningiomatosis and Meningioma in p16INK4a/p19ARF Tumor Suppressor Gene-Deficient Mice
Authors: Morrison James P. , Satoh Hiroshi , Foley Julie , Horton John L. , Dunnick June K. , Kissling Grace E. , Malarkey David E.
Published: October 2007

The cyclin-dependent kinase (CDK) inhibitor p16INK4a and the MDM2 ubiquitin ligase inhibitor p19ARF are critical to the regulation of cell cycle progression. Their loss by deletion, mutation or epigenetic silencing is a common molecular alteration in many human cancers. To investigate the role of p16INK4a/p19ARF deficiency in CNS tumor pathogenesis, pregnant mice bearing p16− /− /p19− /−, p16+ /− /p19+ /−, and p16+ /+ /p19+ /+ embryos were exposed transplacentally on gestation day 14 to a single dose of the potent carcinogen, ethylnitrosourea (ENU). p16+ /− /p19+ /− male mice treated with ENU developed meningial proliferative lesions with a high incidence (5/10). The incidence was lower in other ENU-treated animals of both sexes and none occurred in saline-treated control animals. The lesions ranged from widespread meningeal proliferation and plaque-like thickening by neoplastic spindle cells consistent with meningiomatosis to a larger discrete mass consistent with a meningioma. Ultrastructural analysis revealed the presence of intercellular junctions between cells, supporting a meningothelial histogenesis. Spontaneous meningiomas occur rarely in wild-type mice but are a common neoplasm afflicting humans, accounting for between 13 and 26% of primary intracranial neoplasms. This ENU inducible meningeal lesion in p16+ /− /p19+ /− mice may provide additional insight into the pathogenesis of meningeal neoplasia and aid the development of therapeutics.
Autocrine/paracrine TGFβ1 is required for the development of epidermal Langerhans cells
Authors: Kaplan Daniel H. , Li Ming O. , Jenison Matthew C. , Shlomchik Warren D. , Flavell Richard A. , Shlomchik Mark J.
Published: October 2007

Langerhans cells (LCs) are bone marrow (BM)–derived epidermal dendritic cells (DCs) that develop from precursors found in the dermis. Epidermal LCs are absent in transforming growth factor (TGF) β1-deficient mice. It is not clear whether TGFβ1 acts directly on LC precursors to promote maturation or whether it acts on accessory cells, which in turn affect LC precursors. In addition, the physiologic source of TGFβ1 is uncertain because BM chimera experiments showed that neither hematopoietic nor nonhematopoietic-derived TGFβ1 is required for LC development. To address these issues, we created mice transgenic for a bacterial artificial chromosome (BAC) containing the gene for human Langerin into which Cre recombinase had been inserted by homologous recombination (Langerin-Cre). These mice express Cre selectively in LCs, and they were bred to floxed TGFβRII and TGFβ1 mice, thereby generating mice with LCs that either cannot respond to or generate TGFβ1, respectively. Langerin-Cre TGFβRII mice had substantially reduced numbers of epidermal LCs, demonstrating that TGFβ1 acts directly on LCs in vivo. Interestingly, Langerin-Cre TGFβ1 mice also had very few LCs both in the steady state and after BM transplantation. Thus, TGFβ1 derived from LCs acts directly on LCs through an autocrine/paracrine loop, and it is required for LC development and/or survival.
A Quantitative Description of KcsA Gating I: Macroscopic Currents
Authors: Chakrapani Sudha , Cordero-Morales Julio F , Perozo Eduardo
Published: October 2007

The prokaryotic K+ channel KcsA is activated by intracellular protons and its gating is modulated by transmembrane voltage. Typically, KcsA functions have been studied under steady-state conditions, using macroscopic Rb+-flux experiments and single-channel current measurements. These studies have provided limited insights into the gating kinetics of KcsA due to its low open probability, uncertainties in the number of channels in the patch, and a very strong intrinsic kinetic variability. In this work, we have carried out a detailed analysis of KcsA gating under nonstationary conditions by examining the influence of pH and voltage on the activation, deactivation, and slow-inactivation gating events. We find that activation and deactivation gating of KcsA are predominantly modulated by pH without a significant effect of voltage. Activation gating showed sigmoidal pH dependence with a pKa of ∼4.2 and a Hill coefficient of ∼2. In the sustained presence of proton, KcsA undergoes a time-dependent decay of conductance. This inactivation process is pH independent but is modulated by voltage and the nature of permeant ion. Recovery from inactivation occurs via deactivation and also appears to be voltage dependent. We further find that inactivation in KcsA is not entirely a property of the open-conducting channel but can also occur from partially “activated” closed states. The time course of onset and recovery of the inactivation process from these pre-open closed states appears to be different from the open-state inactivation, suggesting the presence of multiple inactivated states with diverse kinetic pathways. This information has been analyzed together with a detailed study of KcsA single-channel behavior (in the accompanying paper) in the framework of a kinetic model. Taken together our data constitutes the first quantitative description of KcsA gating.
Tarantula Toxins Interact with Voltage Sensors within Lipid Membranes
Authors: Milescu Mirela , Vobecky Jan , Roh Soung H. , Kim Sung H. , Jung Hoi J. , Kim Jae Il , Swartz Kenton J.
Published: October 2007

Voltage-activated ion channels are essential for electrical signaling, yet the mechanism of voltage sensing remains under intense investigation. The voltage-sensor paddle is a crucial structural motif in voltage-activated potassium (Kv) channels that has been proposed to move at the protein–lipid interface in response to changes in membrane voltage. Here we explore whether tarantula toxins like hanatoxin and SGTx1 inhibit Kv channels by interacting with paddle motifs within the membrane. We find that these toxins can partition into membranes under physiologically relevant conditions, but that the toxin–membrane interaction is not sufficient to inhibit Kv channels. From mutagenesis studies we identify regions of the toxin involved in binding to the paddle motif, and those important for interacting with membranes. Modification of membranes with sphingomyelinase D dramatically alters the stability of the toxin–channel complex, suggesting that tarantula toxins interact with paddle motifs within the membrane and that they are sensitive detectors of lipid–channel interactions.
Statistical Backwards Induction: A Simple Method for Estimating Recursive Strategic Models
Authors: Bas Muhammet Ali , Signorino Curtis S. , Walker Robert W.
Published: October 2007

We present a simple method for estimating regressions based on recursive extensive-form games. Our procedure, which can be implemented in most standard statistical packages, involves sequentially estimating standard logits (or probits) in a manner analogous to backwards induction. We demonstrate that the technique produces consistent parameter estimates and show how to calculate consistent standard errors. To illustrate the method, we replicate Leblang's (2003) study of speculative attacks by financial markets and government responses to these attacks.
Integrative feedback and robustness in a lipid biosynthetic network
Authors: Beard Jason , Attard George S , Cheetham Matthew J
Published: October 2007

The homeostatic control of membrane lipid composition appears to be of central importance for cell functioning and survival. However, while lipid biosynthetic reaction networks have been mapped in detail, the underlying control architecture which underpins these networks remains elusive. A key problem in determining the control architectures of lipid biosynthetic pathways, and the mechanisms through which control is achieved, is that the compositional complexity of lipid membranes makes it difficult to determine which membrane parameter is under homeostatic control. Recently, we reported that membrane stored elastic energy provides a physical feedback signal which modulates the activity
in vitro
of CTP:phosphocholine cytidylyltransferase (CCT), an extrinsic membrane enzyme which catalyses a key step in the synthesis of phosphatidylcholine lipids in the Kennedy pathway (Kennedy 1953
J. Am. Chem. Soc
.
75
, 249–250). We postulate that stored elastic energy may be the main property of membranes that is under homeostatic control. Here we report the results of simulations based on this postulate, which reveal a possible control architecture for lipid biosynthesis networks
in vivo
.
Comment on the papers ‘Creep and recrystallization of large polycrystalline masses’ by Faria and co-authors
Authors: Gagliardini Olivier
Published: October 2007

In a series of three papers, Faria and co-authors have presented the application of the theory of mixture with continuous diversity to the creep and recrystallization processes of large polycrystalline masses. In this approach, a material point of the continuum is composed of a huge number of grains defined by their crystallographic orientation. The polycrystal is then seen as a continuous mixture of lattice orientations. All the balance equations are expressed to describe the response of the polycrystal and of a group of crystallites sharing the same lattice orientation (i.e. a species). To go further, Faria and co-authors have to make the hypothesis that the strain rate of every species is equal to the strain rate of the polycrystal, and is therefore independent of its lattice orientation. Furthermore, Faria and co-authors insist on the fact that this hypothesis is
negligible
and has no relation at all to any kind of
Taylor-type
constraint on the deformation of individual grains, arguing that in their theory of strain rate inhomogeneities on the grain level are smeared out because each species is composed of a very large number of crystals. In this comment, I show that the results obtained with a full-field model suggest that this hypothesis is not insignificant.
Yeast forms dominate fungal diversity in the deep oceans
Authors: Bass David , Howe Alexis , Brown Nick , Barton Hannah , Demidova Maria , Michelle Harlan , Li Lily , Sanders Holly , Watkinson Sarah C , Willcock Simon , Richards Thomas A
Published: October 2007

Fungi are the principal degraders of biomass in most terrestrial ecosystems. In contrast to surface environments, deep-sea environmental gene libraries have suggested that fungi are rare and non-diverse in high-pressure marine environments. Here, we report the diversity of fungi from 11 deep-sea samples from around the world representing depths from 1500 to 4000 m (146–388 atm) and two shallower water column samples (250 and 500 m). We sequenced 239 clones from 10 fungal-specific 18S rRNA gene libraries constructed from these samples, from which we detected only 18 fungal 18S-types in deep-sea samples. Our phylogenetic analyses show that a total of only 32 fungal 18S-types have so far been recovered from deep-sea habitats, and our results suggest that fungi, in general, are relatively rare in the deep-sea habitats we sampled. The fungal diversity detected suggests that deep-sea environments host an evolutionarily diverse array of fungi dominated by groups of distantly related yeasts, although four putative filamentous fungal 18S-types were detected. The majority of our new sequences branch close to known fungi found in surface environments. This pattern contradicts the proposal that deep-sea and hydrothermal vent habitats represent ancient ecosystems, and demonstrates a history of frequent dispersal between terrestrial and deep-sea habitats.