bluuebunny/crossref_metadata_2025 huggingface dataset:
Embryology of Eucalyptus Spathulata and E. platypus (Myrtaceae) Following Selfing, Crossing and Reciprocal Interspecific Pollination
Authors: Sedgley M , Granger L
Published: December 2005

Embryology of Eucalyptus spathulata Hook. and E. platypus Hook. (subgenus Symphyomyrtus, section Bisectaria) was investigated by bright field microscopy to determine the cause of ovule failure at 2 months following selfing, crossing and reciprocal interspecific pollination. Eucalyptus spathulata retained more capsules and produced more seeds following cross- than self-pollination, whereas there was no difference between selfing and crossing for E. platypus. Both species produced seeds following interspecific pollination, but germination was low. Highest ovule penetration by a pollen tube, and ovule growth at 2 months, was observed following crossing of E. spathulata and following interspecific pollination of E. platypus. Most self-pollinated ovules of both species were degenerating and were either unfertilised or had undivided zygotes and free nuclear endosperm. Muticellular pro-embryos were more common in cross-pollinated and interspecific pollinated ovules than following selfing. It was concluded that ovule degeneration of E. spathulata and E. platypus following selfing resulted from low levels of pollen tube penetration and fertilisation, and that in those ovules which were fertilised, the zygote generally failed to divide. Degeneration following cross-pollination of E. spathulata also resulted from failure of the zygote to divide, and in E. platypus additional reasons were low levels of pollen tube penetration and fertilisation, and lack of cellularisation of the endosperm. Ovule degeneration of both species following interspecific pollination included failure of the zygote to divide, but in E. spathulata it also resulted from slower embryo development and reduced cellularisation of the endosperm.
Preface to 'Evolution, Extinction and Biogeography in Gondwana'
Authors: Hill Robert S.
Published: December 2005

The macrofossil record of the plant family Cunoniaceae in Australia is
summarised and reviewed where necessary by using detailed studies of the
morphology of extant genera. Eleven of the 26 Cunoniaceae genera are
represented in the Australian macrofossil record and include leaves and leaf
fragments, foliar cuticle and reproductive structures, and range from Late
Paleocene to Quaternary in age. Macrofossils show that some genera had a
different or more widespread distribution in Australia during the Cenozoic,
with two genera (Weinmannia and
Codia) having become extinct from the continent. Changes
in climate, including increasing cold, frost, dryness, seasonality, or some
combination of these, or a reduction in vegetation disturbance regimes (e.g.
volcanism, uplifting, landslips), may be implicated in the regional or
continental extinctions demonstrated by the macrofossil record. Many extant
genera (Schizomeria, Vesselowskya,
Callicoma, Ceratopetalum,
Acsmithia, Codia) had evolved by
the Early Oligocene or earlier (Eucryphia, Late
Paleocene; Ceratopetalum, Middle Eocene), perhaps with
generic diversification more or less complete by the end of the Early Cenozoic
or earlier. A Cretaceous origin of the family is possible, and may account for
its widespread distribution on Southern Hemisphere landmasses, although
long-distance dispersal events are required to explain some modern geographic
disjunctions.
Preparation of 1-[(3-Trifluoromethyl)phenyl]-3,4-dihydro-2(1H)-pyridinone Derivatives from Aza Annulation Reactions of N-[(3-Trifluoromethyl)phenyl]-Substituted Enaminones
Authors: Ali Abdelselam A. , Winzenberg Kevin N.
Published: December 2005

Reaction of 3-trifluoromethylaniline with the 1,3-diketones 1a–1c and 5a–5d affords the N-[(3-trifluoromethyl)phenyl]-substituted enaminones 2a–2c and 6a–6d. Reaction of 2a with the acryloyl chloride derivatives 3a–3c gives the 1-[(3-trifluoromethyl)phenyl]-3,4-dihydro-2(1H)-pyridinones 4a, 4c, 4d; in a similar manner the 2(1H)-pyridinone 4b is obtained from 2b. Reaction of 6c, 6d with acryloyl chloride affords the 2,5(1H,3H)-quinolinedione derivatives 7 and 9 together with the acrylamides 8a, 8b. The 2(1H)-pyridinones 12a, 12b and the 3,4-dihydro-2(1H)-pyridinone 13 are prepared using routes involving the reaction of 2a with ethyl propiolate, dimethyl acetylenedicarboxylate, and maleic anhydride.
Nitrile Oxide Cycloaddition Chemistry Using Benzotriazole as a Steric Auxiliary
Authors: Savage G. Paul , Wernert Gregory T.
Published: December 2005

The relatively hindered 2,2-bis(benzotriazol-1-yl)acetonitrile oxide was prepared in situ from the precursor hydroximinoyl chloride, and was allowed to react with dipolarophiles to give rise to several isoxazoles. The benzotriazole substituents acted as steric auxiliaries to prevent unwanted dimerization of the nitrile oxide to the furoxan by-product.
Synthesis of Some 4-Oxothiochromenes and Related Compounds
Authors: Liepa Andris J. , Nguyen Oanh , Saubern Simon
Published: December 2005

Thiosalicylic acids react with 2-substituted N,N-dialkyl acetamides to give 3-substituted-N,N-dialkyl-2-amino-4-oxothiochromenes 13. N-Alkyl 2-piperidone and analogous caprolactams give derivatives of 1,2,3,4-tetrahydrothiochromeno[2,3-b]pyridin-5-one 16a–16d and 7,8,9,10-tetrahydro-6H-5-thia-6-aza-cyclohepta-[b]naphthalen-11-one 16e, 16f. 2-Mercaptonicotinic acid gave a 1,2,3,4-tetrahydro-9-thia-1,8-diazaanthracen-10-one 16g and a 1,2,3,4-tetrahydro-9-thia-1,8-diazaanthracene-10-thione 16h.
Quaternary Ammonium Arylspiroborate Esters as Organo-Soluble, Environmentally Benign Wood Protectants
Authors: Carr Jenny M. , Duggan Peter J. , Humphrey David G. , Platts James A. , Tyndall Edward M.
Published: December 2005

As part of a larger project aimed at the development of leach resistant boron-based wood preservatives, the anti-fungal and termiticidal activities, and the resistance to leaching from timber, of three related tetra-n-butylammonium spiroborates, tetra-n-butylammonium bis(ortho-hydroxymethylphenolato)borate 2, tetra-n-butylammonium bis[catecholato(2–)-O,O′]borate 3, and tetra-n-butylammonium bis[salicylato(2−)-O,O']borate 4, have been examined. All three borates are found to be active against test organisms, with the following orders of activity being observed: 2 > 3 > 4 > boric acid against wood decay fungi, and 2 > 3 ≈ 4 > boric acid against termites. The most active compound in both assays 2 also has the highest calculated lipophilicity. In a test for permanence in wood, the following order of leach resistance is observed: 4 >> 3 ≈ 2 > boric acid. This order appears to correlate more closely with the stability constants of the borate esters, as determined using 11B NMR spectroscopy, rather than calculated lipophilicities.
Evaluation of Aqueous Extracts from Elast-Eon Polymers for Methylene Dianiline (MDA) by High-Performance Liquid Chromatography (HPLC)
Authors: Mudumba Ramasri , Padsalgikar Ajay D. , Littler Stuart W.
Published: December 2005

Elast-Eon polymers are a class of materials suitable for use in long-term implantable medical devices. They are the copolymers of methylene diphenyl diisocyanate (MDI) based polyurethanes and hydroxyl-terminated polydimethyl siloxane, and as a result combine the biostability and biocompatibility of silicones with the mechanical properties of polyurethanes. In order to ensure product safety and meet regulatory requirements, it is important to confirm the absence or presence of toxic 4,4′-methylene dianiline (MDA) in aqueous extracts of Elast-Eon. The present work focusses on the development of an analytical technique to detect any leachable MDA from Elast-Eon polymers. No traces of MDA could be detected in the aqueous extracts from Elast-Eon, or from sterilized and aged (accelerated oxidized) samples of Elast-Eon.
Factors affecting the detection of possums by spotlighting in Western Australia
Authors: Wayne A. F. , Cowling A. , Rooney J. F. , Ward C. G. , Wheeler I. B. , Lindenmayer D.B. , Donnelly C. F.
Published: December 2005

This paper describes how environmental factors, survey method procedures and differences in forest structure resulting from logging relate to the detection of koomal (common brushtail possum, Trichosurus vulpecula hypoleucus) and ngwayir (western ringtail possum, Pseudocheirus occidentalis). A total of 169 vehicle-based spotlight surveys of possums within native jarrah (Eucalyptus marginata) forest was conducted on three transects over eight years (1996–2003). Up to 5.7 koomal and up to 3.3 ngwayir were detected per kilometre per transect side. Only one ngwayir was detected during the eight surveys conducted between 2001 and 2003. More koomal were seen in spring and autumn (i.e. September–November and March–May respectively) and more ngwayir were seen between October and April. Although surveys were not conducted on very rainy or excessively windy nights, fewer possums were nonetheless seen on nights following rainy days and on cold nights. Cloud cover also affected sightings of koomal. The time taken to complete the surveys increased in conjunction with the number of possums detected, on account of the time required to record data. The importance of standardising travelling speed also is emphasised. Possum spotlight counts differed between recently logged and unlogged areas. However, these findings were not supported by complementary koomal abundance estimates derived from trapping, suggesting that vegetation structure may affect detectability. Factors such as the lunar cycle, wind speed and survey start time after sunset did not significantly affect detection rates of either species. On the basis of these findings, specific survey conditions can be selected to improve spotlight detection efficiency.
The immediate impact of 1080 aerial baiting to control wild dogs on a spotted-tailed quoll population
Authors: Körtner Gerhard , Watson Peter
Published: December 2005

In eastern Australia, the spotted-tailed quoll (Dasyurus maculatus) is the species thought to be most likely at risk from aerial baiting with compound 1080 to control wild dogs (Canis lupus familiaris and C. l. dingo). Although it is known that quolls occasionally die of 1080 poisoning, the broader impact on populations remains unresolved. We therefore assessed the impact of a regular aerial baiting campaign on a population of spotted-tailed quolls. Baiting with 1080 meat baits was conducted by the local Wild Dog Control Association and followed the same procedure as in previous years with the exception that the biomarker, rhodamine B, was added to the baits. Prior to the baiting, 36 quolls were trapped and fitted with mortality radio-collars; 31 of these collars were still functional at the time of baiting. Quolls were monitored from a helicopter and on the ground until retrapped 5–9 weeks after baiting. Transmitters were then removed and a sample of vibrissae was taken for rhodamine B analysis. Carcasses found were analysed for 1080. Predator numbers were assessed before and after baiting using track pads across trails. Among the initial 36 radio-collared quolls, nine mortalities were recorded during the course of the study (seven after baiting). Only one of the nine deaths could be directly attributed to 1080 poisoning. In addition, vibrissae from five of the 35 individuals sampled after baiting were marked with rhodamine B, indicating that these individuals had consumed bait, and survived. Consequently, mortality attributable to this particular aerial baiting campaign was low, apparently because few quolls ate bait and most of those that did survived. Track counts for predators indicated a significant decrease in dog and fox numbers after baiting. Cat activity remained unchanged and the number of quoll tracks increased.
Widespread genetic exchange among terrestrial bacteriophages
Authors: Silander Olin K. , Weinreich Daniel M. , Wright Kevin M. , O'Keefe Kara J. , Rang Camilla U. , Turner Paul E. , Chao Lin
Published: December 2005

Bacteriophages are the most numerous entities in the biosphere. Despite this numerical dominance, the genetic structure of bacteriophage populations is poorly understood. Here, we present a biogeography study involving 25 previously undescribed bacteriophages from the Cystoviridae clade, a group characterized by a dsRNA genome divided into three segments. Previous laboratory manipulation has shown that, when multiple Cystoviruses infect a single host cell, they undergo (
i
) rare intrasegment recombination events and (
ii
) frequent genetic reassortment between segments. Analyzing linkage disequilibrium (LD) within segments, we find no significant evidence of intrasegment recombination in wild populations, consistent with (
i
). An extensive analysis of LD between segments supports frequent reassortment, on a time scale similar to the genomic mutation rate. The absence of LD within this group of phages is consistent with expectations for a completely sexual population, despite the fact that some segments have >50% nucleotide divergence at 4-fold degenerate sites. This extraordinary rate of genetic exchange between highly unrelated individuals is unprecedented in any taxa. We discuss our results in light of the biological species concept applied to viruses.
Network of dendritic cells within the muscular layer of the mouse intestine
Authors: Flores-Langarica Adriana , Meza-Perez Selene , Calderon-Amador Juana , Estrada-Garcia Teresa , MacPherson Gordon , Lebecque Serge , Saeland Sem , Steinman Ralph M. , Flores-Romo Leopoldo
Published: December 2005

Dendritic cells (DCs) are located at body surfaces such as the skin, respiratory and genital tracts, and intestine. To further analyze intestinal DCs, we adapted an epidermal sheet separation technique and obtained two intestinal layers, facing the lumen and serosa. Unexpectedly, immunolabeling of the layer toward the serosa revealed a regular, dense, planar network of cells with prominent dendritic morphology within the external muscular layer and with increasing frequency along the length of the intestine. Direct examination of the serosal-disposed layers showed a significant fraction of the DCs to express DEC-205/CD205, CD11c, Langerin/CD207, Fcγ receptor/CD16/32, CD14, and low levels of activation markers, CD25, CD80, CD86, and CD95. By more sensitive FACS analyses, cells from this layer contained two CD11c+populations of CD45+CD205+, CD19-leukocytes, MHC II+and MHC II-. When ovalbumin conjugated to an anti-DEC-205 antibody was injected into mice, the conjugate targeted to these DCs, which upon isolation were able to stimulate ovalbumin-specific, CD4+and CD8+T cell antigen receptor-transgenic T cells.In vivo, these DCs responded to two microbial stimuli, systemic LPS and oral live bacteria, by up-regulating CD80, CD86, DEC-205, and Langerin within 12 h. This network of DCs thus represents a previously unrecognized antigen-presenting cell system in the intestine.
Disruption of Cryptochrome partially restores circadian rhythmicity to the arrhythmic
period
mutant of
Drosophila
Authors: Collins Ben H. , Dissel Stephane , Gaten Edward , Rosato Ezio , Kyriacou Charalambos P.
Published: December 2005

The
Drosophila melanogaster
circadian clock is generated by interlocked feedback loops, and null mutations in core genes such as
period
and
timeless
generate behavioral arrhythmicity in constant darkness. In light-dark cycles, the elevation in locomotor activity that usually anticipates the light on or off signals is severely compromised in these mutants. Light transduction pathways mediated by the rhodopsins and the dedicated circadian blue light photoreceptor cryptochrome are also critical in providing the circadian clock with entraining light signals from the environment. The

cry
b

mutation reduces the light sensitivity of the fly's clock, yet locomotor activity rhythms in constant darkness or light-dark cycles are relatively normal, because the rhodopsins compensate for the lack of cryptochrome function. Remarkably, when we combined a
period
-null mutation with

cry
b

, circadian rhythmicity in locomotor behavior in light-dark cycles, as measured by a number of different criteria, was restored. This effect was significantly reduced in
timeless
-null mutant backgrounds. Circadian rhythmicity in constant darkness was not restored, and TIM protein did not exhibit oscillations in level or localize to the nuclei of brain neurons known to be essential for circadian locomotor activity. Therefore, we have uncovered residual rhythmicity in the absence of
period
gene function that may be mediated by a previously undescribed
period
-independent role for
timeless
in the
Drosophila
circadian pacemaker. Although we do not yet have a molecular correlate for these apparently iconoclastic observations, we provide a systems explanation for these results based on differential sensitivities of subsets of circadian pacemaker neurons to light.
Opioid-induced tolerance and dependence in mice is modulated by the distance between pharmacophores in a bivalent ligand series
Authors: Daniels David J. , Lenard Natalie R. , Etienne Chris L. , Law Ping-Yee , Roerig Sandra C. , Portoghese Philip S.
Published: December 2005

Given the mounting evidence for involvement of δ opioid receptors in the tolerance and physical dependence of μ opioid receptor agonists, we have investigated the possible physical interaction between μ and δ opioid receptors by using bivalent ligands. Based on reports of suppression of antinociceptive tolerance by the δ antagonist naltrindole (NTI), bivalent ligands [μ-δ agonist-antagonist (MDAN) series] that contain different length spacers, and pharmacophores derived from NTI and the μ agonist oxymorphone, have been synthesized and evaluated by intracerebroventricular (i.c.v.) administration in the tail-flick test in mice. In acute i.c.v. studies, the bivalent ligands functioned as agonists with potencies ranging from 1.6- to 45-fold greater than morphine. In contrast, the monovalent μ agonist analogues were substantially more potent than the MDAN congeners and were essentially equipotent with one another and oxymorphone. Pretreatment with NTI decreased the ED50values for MDAN-19 to a greater degree than for MDAN-16 but had no effect on MDAN-21. Chronic i.c.v. studies revealed that MDAN ligands whose spacer was 16 atoms or longer produced less dependence than either morphine or μ monovalent control MA-19. On the other hand, both physical dependence and tolerance were suppressed at MDAN spacer lengths of 19 atoms or greater. These data suggest that physical interaction between the μ and δ opioid receptors modulates μ-mediated tolerance and dependence. Because MDAN-21 was found to be 50-fold more potent than morphine by the i.v. route (i.v.), it offers a previously uncharacterized approach for the development of analgesics devoid of tolerance and dependence.
Class II-restricted T cell receptor engineeredin vitrofor higher affinity retains peptide specificity and function
Authors: Weber K. Scott , Donermeyer David L. , Allen Paul M. , Kranz David M.
Published: December 2005

The T cell receptor (TCR) αβ heterodimer determines the peptide and MHC specificity of a T cell. It has been proposed thatin vivoselection processes maintain low TCR affinities because T cells with higher-affinity TCRs would (i) have reduced functional capacity or (ii) cross-react with self-peptides resulting in clonal deletion. We used the class II-restricted T cell clone 3.L2, specific for murine hemoglobin (Hb/I-Ek), to explore these possibilities by engineering higher-affinity TCR mutants. A 3.L2 single-chain TCR (Vβ-linker-Vα) was mutagenized and selected for thermal stability and surface expression in a yeast display system. Stabilized mutants were used to generate a library with CDR3 mutations that were selected with Hb/I-Ekto isolate a panel of affinity mutants withKDvalues as low as 25 nM. Kinetic analysis of soluble single-chain TCRs showed that increased affinities were the result of both faster on-rates and slower off-rates. T cells transfected with the mutant TCRs and wild-type TCR responded to similar concentrations of peptide, indicating that the increased affinity was not detrimental to T cell activation. T cell transfectants maintained exquisite hemoglobin peptide specificity, but an altered peptide ligand that acted as an antagonist for the wild-type TCR was converted to a strong agonist with higher-affinity TCRs. These results show that T cells with high-affinity class II reactive TCRs are functional, but there is an affinity threshold above which an increase in affinity does not result in significant enhancement of T cell activation.
Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone
Authors: Karst Henk , Berger Stefan , Turiault Marc , Tronche Francois , Schütz Günther , Joëls Marian
Published: December 2005

The adrenal hormone corticosterone transcriptionally regulates responsive genes in the rodent hippocampus through nuclear mineralocorticoid and glucocorticoid receptors. Via this genomic pathway the hormone alters properties of hippocampal cells slowly and for a prolonged period. Here we report that corticosterone also rapidly and reversibly changes hippocampal signaling. Stress levels of the hormone enhance the frequency of miniature excitatory postsynaptic potentials in CA1 pyramidal neurons and reduce paired-pulse facilitation, pointing to a hormone-dependent enhancement of glutamate-release probability. The rapid effect by corticosterone is accomplished through a nongenomic pathway involving membrane-located receptors. Unexpectedly, the rapid effect critically depends on the classical mineralocorticoid receptor, as evidenced by the effectiveness of agonists, antagonists, and brain-specific inactivation of the mineralocorticoid but not the glucocorticoid receptor gene. Rapid actions by corticosterone would allow the brain to change its function within minutes after stress-induced elevations of corticosteroid levels, in addition to responding later through gene-mediated signaling pathways.
The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice
Authors: Aharoni Rina , Eilam Raya , Domev Hagit , Labunskay Galya , Sela Michael , Arnon Ruth
Published: December 2005

Neurotrophins (NTs) such as BDNF, NT-3, and NT-4 are important modulators of neuronal function and survival. Their expression in the CNS after various insults is thus of major therapeutic consequence. Glatiramer acetate [(GA) Copaxone], an approved drug for the treatment of multiple sclerosis, has been shown to induce Th2/3 cells that accumulate in the CNS, expressing
in situ
antiinflammatory cytokines and BDNF. In the present study, we investigated whether s.c. injections of GA, applied at various stages of experimental autoimmune encephalomyelitis, affect the expression of NTs, particularly BDNF, in the brain. In untreated experimental autoimmune encephalomyelitis mice, the expression of NTs was elevated shortly after disease appearance but subsequently declined below that of naive mice. In contrast, GA treatment led to sustained augmentation in the expression of BDNF, NT-3, and NT-4 in various brain regions as demonstrated by histological analysis of immunostained brain sections. GA treatment, even when started 45 days after disease induction, restored the impaired level of NTs to that of healthy mice. BDNF elevation after GA treatment was demonstrated on both protein and mRNA levels. Prominent staining was manifested not only by infiltrating GA-induced T cells, but also by CNS resident cells (neurons and astrocytes), indicative of a bystander therapeutic effect. Of importance, in GA-treated mice, intense BDNF expression was manifested by neuronal progenitors that migrated into lesions in injured regions. These results indicate that the immunomodulator GA exerts not only an antiinflammatory effect, but also enhances neuroprotection and regeneration of neural elements in the diseased brain.
Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 Å
Authors: Lee John K. , Kozono David , Remis Jonathan , Kitagawa Yoshichika , Agre Peter , Stroud Robert M.
Published: December 2005

To explore the structural basis of the unique selectivity spectrum and conductance of the transmembrane channel protein AqpM from the archaeon
Methanothermobacter marburgensis
, we determined the structure of AqpM to 1.68-Å resolution by x-ray crystallography. The structure establishes AqpM as being in a unique subdivision between the two major subdivisions of aquaporins, the water-selective aquaporins, and the water-plus-glycerol-conducting aquaglyceroporins. In AqpM, isoleucine replaces a key histidine residue found in the lumen of water channels, which becomes a glycine residue in aquaglyceroporins. As a result of this and other side-chain substituents in the walls of the channel, the channel is intermediate in size and exhibits differentially tuned electrostatics when compared with the other subfamilies.
Up-regulation of a H
+
-pyrophosphatase (H
+
-PPase) as a strategy to engineer drought-resistant crop plants
Authors: Park Sunghun , Li Jisheng , Pittman Jon K. , Berkowitz Gerald A. , Yang Haibing , Undurraga Soledad , Morris Jay , Hirschi Kendal D. , Gaxiola Roberto A.
Published: December 2005

Engineering drought -resistant crop plants is a critically important objective. Overexpression of the vacuolar H
+
-pyrophosphatase (H
+
-PPase) AVP1 in the model plant
Arabidopsis thaliana
results in enhanced performance under soil water deficits. Recent work demonstrates that AVP1 plays an important role in root development through the facilitation of auxin fluxes. With the objective of improving crop performance, we expressed AVP1 in a commercial cultivar of tomato. This approach resulted in (
i
) greater pyrophosphate-driven cation transport into root vacuolar fractions, (
ii
) increased root biomass, and (
iii
) enhanced recovery of plants from an episode of soil water deficit stress. More robust root systems allowed transgenic tomato plants to take up greater amounts of water during the imposed water deficit stress, resulting in a more favorable plant water status and less injury. This study documents a general strategy for improving drought resistance of crops.
The growth of business firms: Theoretical framework and empirical evidence
Authors: Fu Dongfeng , Pammolli Fabio , Buldyrev S. V. , Riccaboni Massimo , Matia Kaushik , Yamasaki Kazuko , Stanley H. Eugene
Published: December 2005

We introduce a model of proportional growth to explain the distribution

P
g
(g)

of business-firm growth rates. The model predicts that

P
g
(g)

is exponential in the central part and depicts an asymptotic power-law behavior in the tails with an exponent ζ = 3. Because of data limitations, previous studies in this field have been focusing exclusively on the Laplace shape of the body of the distribution. In this article, we test the model at different levels of aggregation in the economy, from products to firms to countries, and we find that the predictions of the model agree with empirical growth distributions and size-variance relationships.
Absolute rate theories of epigenetic stability
Authors: Walczak Aleksandra M. , Onuchic José N. , Wolynes Peter G.
Published: December 2005

Spontaneous switching events in most characterized genetic switches are rare, resulting in extremely stable epigenetic properties. We show how simple arguments lead to theories of the rate of such events much like the absolute rate theory of chemical reactions corrected by a transmission factor. Both the probability of the rare cellular states that allow epigenetic escape and the transmission factor depend on the rates of DNA binding and unbinding events and on the rates of protein synthesis and degradation. Different mechanisms of escape from the stable attractors occur in the nonadiabatic, weakly adiabatic, and strictly adiabatic regimes, characterized by the relative values of those input rates.
Evidence by molecular profiling for a placental origin of infantile hemangioma
Authors: Barnés Carmen M. , Huang Sui , Kaipainen Arja , Sanoudou Despina , Chen Emy J. , Eichler Gabriel S. , Guo Yuchun , Yu Ying , Ingber Donald E. , Mulliken John B. , Beggs Alan H. , Folkman Judah , Fishman Steven J.
Published: December 2005

The origin of the pathogenic endothelial cells in common infantile hemangioma is unknown. We show here that the transcriptomes of human placenta and infantile hemangioma are sufficiently similar to suggest a placental origin for this tumor, expanding on recent immunophenotypical studies that have suggested this possibility [North, P. E.,
et al.
(2001)
Arch. Dermatol.
137, 559-570]. The transcriptomes of placenta, hemangioma, and eight normal and diseased tissues were compared by hierarchical and nonhierarchical clustering analysis of >7,800 genes. We found that the level of transcriptome similarity between placenta and hemangioma exceeded that of any other tissue compared and paralleled that observed between a given tissue and its derived tumor, such as normal and cancerous lung. The degree of similarity was even greater when a subset of endothelial cell-specific genes was analyzed. Genes preferentially expressed in both placenta and hemangiomas were identified, including 17-β hydroxysteroid dehydrogenase type 2 and tissue factor pathway inhibitor 2. These data demonstrate the value of global molecular profiling of tissues as a tool for hypothesis-driven research. Furthermore, it suggests that the unique self-limited growth of infantile hemangioma may, in fact, mirror the lifetime of placental endothelium.
The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1receptor coupling to Gq/11G proteins
Authors: Lauckner Jane E. , Hille Bertil , Mackie Ken
Published: December 2005

Central nervous system responses to cannabis are primarily mediated by CB1receptors, which couple preferentially to Gi/oG proteins. Here, we used calcium photometry to monitor the effect of CB1activation on intracellular calcium concentration. Perfusion with 5 μM CB1aminoalkylindole agonist, WIN55,212-2 (WIN), increased intracellular calcium by several hundred nanomolar in human embryonic kidney 293 cells stably expressing CB1and in cultured hippocampal neurons. The increase was blocked by coincubation with the CB1antagonist, SR141716A, and was absent in nontransfected human embryonic kidney 293 cells. The calcium rise was WIN-specific, being essentially absent in cells treated with other classes of cannabinoid agonists, including Δ9-tetrahydrocannabinol, HU-210, CP55,940, 2-arachidonoylglycerol, methanandamide, and cannabidiol. The increase in calcium elicited by WIN was independent of Gi/o, because it was present in pertussis toxin-treated cells. Indeed, pertussis toxin pretreatment enhanced the potency and efficacy of WIN to increase intracellular calcium. The calcium increases appeared to be mediated by GqG proteins and phospholipase C, because they were markedly attenuated in cells expressing dominant-negative Gqor treated with the phospholipase C inhibitors U73122 and ET-18-OCH3and were accompanied by an increase in inositol phosphates. The calcium increase was blocked by the sarco/endoplasmic reticulum Ca2+pump inhibitor thapsigargin, the inositol trisphosphate receptor inhibitor xestospongin D, and the ryanodine receptor inhibitors dantrolene and 1,1′-diheptyl-4,4′-bipyridinium dibromide, but not by removal of extracellular calcium, showing that WIN releases calcium from intracellular stores. In summary, these results suggest that WIN stabilizes CB1receptors in a conformation that enables Gqsignaling, thus shifting the G protein specificity of the receptor.
A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis
Authors: Malins Donald C. , Gilman Naomi K. , Green Virginia M. , Wheeler Thomas M. , Barker Edward A. , Anderson Katie M.
Published: December 2005

A cancer DNA phenotype, identical to the DNA structure of tumors, has been identified in the prostate glands of certain healthy men over 55 years of age. We now show that the same DNA signature exists in normal tissues adjacent to tumors. This finding implies that the phenotype is maintained in normal prostate cells from its inception through tumor development. The presence of the phenotype in tumors, adjacent normal cells, and in the normal prostate cells of certain older men suggests that it is a potentially critical factor in tumor development and may serve as an early biomarker for cancer risk assessment. Intervention to inhibit the development of the phenotype in healthy men, or to eliminate it once formed, may suppress or even prevent tumor formation.
A MAPK gene from Dead Sea fungus confers stress tolerance to lithium salt and freezing–thawing: Prospects for saline agriculture
Authors: Jin Yan , Weining Song , Nevo Eviatar
Published: December 2005

The Dead Sea is one of the most saline lakes on earth (≈340 g/liter salinity) and is ≈10 times saltier than the oceans.
Eurotium herbariorum
, a common fungal species, was isolated from its water. EhHOG gene, encoding a mitogen-activated protein kinase (MAPK) that plays an essential role in the osmoregulatory pathway in yeast and many other eukaryotes, was isolated from
E. herbariorum
. The deduced amino acid sequences of EhHOG indicated high similarity with homologous genes from
Aspergillus nidulans
,
Saccharomyces cerevisiae
, and
Schizosaccharomyces pombe
and contained a TGY motif for phosphorylation by MAPK kinase. When EhHOG was expressed in
S. cerevisiae hog1
Δ mutant, the growth and aberrant morphology of
hog1
Δ mutant was restored under high osmotic stress condition. Moreover, intracellular glycerol content in the transformant increased to a much higher level than that in the mutant during salt-stress situations.
hog1
Δ mutant complemented by EhHOG outperformed the wild type or had higher genetic fitness under high Li
+
and freezing–thawing conditions. The present study revealed the putative presence of a high-osmolarity glycerol response (HOG) pathway in
E. herbariorum
and the significance of
EhHOG
in osmotic regulation, heat stress, freeze stress, and oxidative stress. The Dead Sea is becoming increasingly more saline while the fungi living in it evolutionarily adapt to its high-saline environment, particularly with the extraordinarily high Li
+
concentration. The Dead Sea is potentially an excellent model for studies of evolution under extreme environments and is an important gene pool for future agricultural genetic engineering prospects.
Increasing Ca
2+
transients by broadening postsynaptic action potentials enhances timing-dependent synaptic depression
Authors: Zhou Yu-Dong , Acker Corey D. , Netoff Theoden I. , Sen Kamal , White John A.
Published: December 2005

Repeated induction of pre- and postsynaptic action potentials (APs) at a fixed time difference leads to long-term potentiation (LTP) or long-term depression (LTD) of the synapse, depending on the temporal order of pre- and postsynaptic activity. This phenomenon of spike-timing-dependent plasticity (STDP) is believed to arise by nonlinear processes that lead to larger calcium transients (and thus LTP) when presynaptic APs precede postsynaptic APs and smaller calcium transients (and thus LTD) when postsynaptic APs precede presynaptic APs. In contrast to predictions from such calcium-peak-detector models, we show that constitutively or artificially broadened APs in layer II/III pyramidal cells of entorhinal cortex (EC) lead to an increase in the dendritic calcium transient and shift the balance of STDP toward LTD. STDP in entorhinal pyramidal cells is NMDA-receptor-dependent and modulated by the Ca
V
1Ca
2+
channel-blocker nifedipine. Results are consistent with an elaboration of the calcium-peak-detector model in which downstream signals from voltage-dependent Ca
2+
channels suppress LTP relative to LTD. Our results suggest that modulation of AP width is a potent way to adjust the rules of synaptic plasticity in the EC.
Natural medicines for alcoholism treatment: a review
Authors: XU B. J. , ZHENG Y. N. , SUNG C. K.
Published: December 2005

Alcoholism is a serious problem throughout the world. The development of alcoholism remedies have medical, social and economical significance. In view of the pitfalls of psychological dependence and adverse behavioural effects of synthetic drugs, the development of low toxicity and high efficiency medicines derived from natural products exhibits expansive market prospects. Based on these considerations, we summarize briefly folk application of traditional hangover remedies and clinical application of herbal complex and patent medicines for alcoholism treatment. We have reviewed the effects of natural medicines on intake, absorption and metabolism of alcohol, as well as the protective effects on alcohol‐induced acute and chronic tissue injury.
The strategic and political consequences of using demographic criteria for the organization of European leagues
Authors: Durand Christophe , Ravenel Loïc , Bayle Emmanuel
Published: December 2005

The hypothesis of the Americanization of European club sports competitions has been the subject of much analysis. The main concept examined in this article is the growing reliance on demographic criteria, particularly the economic potential of the market zone. The purpose is to consider the consequences (rather than the likelihood) of a scenario in which demographic criteria become the sole variables of club location and their qualification in European championships. Such a change would have consequences for the both the private (shareholders or potential investors, direct supporters or general audience, sponsors, etc.) and public (federations, local government, states, European governing bodies) sectors.

The first part of the paper reviews the relevant demographic criteria in sports and then recalls the current strategies for league organization on both sides of the Atlantic. The second part is devoted to assessing the consequences of these strategies for those involved. General questions are then raised about the future of professional sports teams in Europe.

The analytical method is based on principles taken from demographics, geomarketing (as geographic information system, GIS) and the political economy of sport. The data concern six major leagues on both sides of the Atlantic.
Sport and the welfare state in Europe
Authors: Heinemann Klaus
Published: December 2005

The article analyses the mutual interconnection between welfare states and sports systems in six European countries (Denmark, Great Britain, Germany, France, Italy, Spain). It seeks to address, on the one hand, questions such as the following: what were the underlying rationales and ideologies evident in the justification of sports policy in welfare frameworks? What cultural values, historical contexts, and political configurations were evident in the specific arrangements of a given welfare state and its governmental welfare poicy infrastructure? On the other hand it portrays the legal, institutional and organisational similarities and dissimilarities which exist in a given country between the institutional structure of the sport system and the organisation of the welfare state, and seeks to identify to what extent comparable structural elements have developed, and where dissimilarities can be found.

This paper illustrates how, where sports and welfare systems in different European countries are derived from different historical roots and are based on different ideologies and organisational structures, the welfare state maintains a different position and influence on sport. To the extent that the traditional welfare states of western industrialised countries are heading towards crises in terms of increasing funding requirements and legitimation deficits, the sport system will also be affected by the immediate consequences of such developments and will be required to adjust and adapt.
The governance of professional soccer: Five case studies – Algeria, China, England, France and Japan
Authors: Amara Mahfoud , Henry Ian , Liang Jin , Uchiumi Kazuo
Published: December 2005

Although there has been a rapid growth in the globalisation of sport and its delivery to world markets, nevertheless there is a variety of models of sport‐business whose characteristics are the product of local histories, local political and sporting cultures, local economic conditions and so on. This paper does not seek to deny the increasingly obvious impact of globalisation on professional sport, but rather it seeks to articulate the ways in which such global phenomena are locally mediated in professional soccer systems in five countries, to identify and to explain local responses to global pressures. The five examples include the oldest professional football system, that of England, and a second contrasting European system, France, together with three relatively recently established professional football systems in Japan a developed capitalist economy, Algeria, which is developing a post‐socialist sports economy, and China which is experimenting in sport as in other areas with a ‘socialist market economy’. The resultant evolution of professional sporting systems represents distinctive configurations of stakeholders in what are in effect contrasting business models, and reflects a situation of ‘diminishing varieties and increasing contrasts’, in contrast to the claims made by Elias in relation to global cultural phenomena.
The organisational performance of national swimming federations in Mediterranean countries: A comparative approach
Authors: Madella A. , Bayle E. , Tome J.
Published: December 2005

This paper confronts the basic questions involved in the measurement of the performance of national sport organisations through a specific approach conceived and carried out for national swimming federations in four Mediterranean countries (Italy, Greece, Portugal and Spain). In the past there has been a number of studies assessing the effectiveness or the performance of NSOs (national sporting organisations/national governing bodies/national sport federations), but these were predominantly descriptive, specific to a particular point in time, and were not related to the establishment of a stable measurement system for management control. Performance is viewed here, in a broad sense, as the ability to acquire and process human, financial and physical resources to achieve the goals of the organisation. To measure a multidimensional performance we propose to use a specific model with a systemic approach (applied from Madella, A. (1998). La performance di successo delle organizzazioni‐Spunti di riflessione per gestire efficacemente le società di atletica leggera.Atleticastudi, 101–112). This approach combines at the same time, input and process variables and output measures.

The final data collected, incorporate five basic dimensions: human resources, finance, institutional communication, partnership and inter‐organisational relations, volume and quality of services, and athletes’ international performance. An analysis of the global performance of each federation is illustrated. Finally interviews with key actors are used to identify some of the principal factors of success of performance.
Relationship between before‐to‐after‐exercise feeling state changes and exercise session attendance over 14 weeks: Testing principles of Operant Conditioning
Authors: Annesi James J.
Published: December 2005

A preliminary field study was conducted to estimate relationships between changes in feelings states occurring from before to after 20‐ to 30‐min bouts of moderate cardiovascular exercise, and two measures of adherence to exercise in 66 adults (M age=38 yrs, 30% males) initiating regimens of 3x/week. Positive pre‐ to post‐exercise changes in participants’ feeling state scores ranged from 0 to 100% (M=73.2%, SD=28.8). Significant positive correlations were found between percentage of positive changes and exercise session attendance (r=0.36, p=0.003), and number of days of adherence to exercise (r=0.37, p=0.002), over 14 weeks. Results were interpreted as supporting principles of operant conditioning, and the possibility of exercise‐induced feeling changes having direct reinforcing and punishing properties on the behavior of exercise in adults initiating programs. Accounting for identified correlates of exercise maintenance was suggested for extensions of this research. Applied uses of the abbreviated feeling state measure adapted for this research were suggested, after sufficient replication.
Keratin 8 overexpression promotes mouse Mallory body formation
Authors: Nakamichi Ikuo , Toivola Diana M. , Strnad Pavel , Michie Sara A. , Oshima Robert G. , Baribault Hélène , Omary M. Bishr
Published: December 2005

Keratins 8 and 18 (K8/18) are major constituents of Mallory bodies (MBs), which are hepatocyte cytoplasmic inclusions seen in several liver diseases. K18-null but not K8-null or heterozygous mice form MBs, which indicates that K8 is important for MB formation. Early stages in MB genesis include K8/18 hyperphosphorylation and overexpression. We used transgenic mice that overexpress K8, K18, or K8/18 to test the importance of K8 and/or K18 in MB formation. MBs were induced by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Livers of young K8 or K8/K18 overexpressors had no histological abnormalities despite increased keratin protein and phosphorylation. In aging mice, only K8-overexpressing livers spontaneously developed small “pre-MB” aggregates. Only K8-overexpressing young mice are highly susceptible to MB formation after short-term DDC feeding. Thus, the K8 to K18 ratio, rather than K8/18 overexpression by itself, plays an essential role in MB formation. K8 overexpression is sufficient to form pre-MB and primes animals to accumulate MBs upon DDC challenge, which may help explain MB formation in human liver diseases.
Implantation of the Ossified Cochlea: Management with the Split Electrode Array
Authors: Millar D A. , Hillman Todd A. , Shelton Clough
Published: December 2005

Objectives/Hypothesis: To describe indications for, the surgical technique required, and the expected functional results of split electrode array cochlear implants.

Study Design: Retrospective chart review.

Methods: Data collected included etiology of deafness, radiographic findings, pre‐ and postoperative aided pure tone thresholds, and speech perception testing. Adult speech perception outcomes were measured using the Consonant Nucleus Consonant (CNC) monosyllable words and Hearing in Noise Test (HINT) in quiet/noise (+10dB). The children were assessed using the Infants and Toddlers Meaningful Auditory Integration Scale.

Results: Five patients were implanted with a split electrode array. This included two adults and three children. Both adults had preoperative binaural aided pure tone averages worse than 50d B and scores of 0% on both HINT quiet and CNC words. The children had undetectable preoperative aided thresholds and scored an average 4/40 on the IT‐MAIS. Postimplant, the average threshold gain was 38.5 dB in the adults and 81.5 dB in the children. One adult improved to score 51%/22% on HINT quiet/noise at 6 months and 72%/30% at 12 months. The other adult continued to score 0% on HINT at 12 months but claimed substantial subjective auditory improvement after the first year of device use. The children averaged 28/40 on the IT MAIS at 6 months after implantation. Forty‐two of 48 implanted electrodes were functional.

Conclusions: The split electrode array is a useful alternative to traditional cochlear implants in treating deafened patients with cochlear ossification. Patients implanted with the split array show marked improvement in sound and speech perception.