bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial observations of increased requirements for light-energy dissipation in ryegrass (Lolium perenne) when source/sink ratios become high at a naturally grazed free air CO2 enrichment (FACE) site
Authors: Guo Jianmin , Trotter Craig M. , Newton Paul C. D.
Published: November 2006

Although photosynthetic response to long-term elevated CO2 has been extensively studied, little attention has yet been directed at coordinated adjustments between the use of absorbed light for CO2 fixation, and the dissipation of potentially harmful excess light. In this study, we have performed an initial analysis of photosynthetic light use and excess light dissipation in response to grazing-induced variation in the source / sink ratio in ryegrass (Lolium perenne L.) after 6 years’ exposure to Free Air CO2 Enrichment (FACE). Before grazing, when the source / sink ratio was relatively large, significant down-regulation of photosynthetic capacity (Amax) was observed in the FACE leaves compared with control leaves at the same stage of maturity. The decrease in Amax partly offset the direct stimulation of elevated CO2 on light-saturated photosynthesis, and was accompanied by a reduction in photochemical electron flow that was accompanied by a large increase in susceptibility to photoinhibition. This was indicated by large increases in both non-photochemical quenching (NPQ) and the de-epoxidised state of xanthophyll cycle (DEPS), and also by changes in the photochemical reflectance index (PRI). However, no significant increase in the xanthophyll pool size in FACE leaves was observed, despite the apparent large increase in requirements for photodissipation in FACE leaves. After grazing, when the source / sink ratio was relatively small, the CO2 fixation rates in both the FACE and control leaves were, as expected, significantly higher compared with those before grazing, and there was no down-regulation of photosynthetic capacity in the leaves under FACE conditions. In addition, the extent of photodissipation in the FACE and control leaves was not significantly different. Overall, the profile of leaf physiological and biochemical responses supports the hypothesis that the effect of long-term elevated CO2 can be significantly influenced by short-term variation in the source / sink ratio. As the xanthophyll pool size does not change significantly, this poses the question of whether the increased photodissipative demand observed here under even moderately elevated CO2 concentrations may lead to increased plant susceptibility to photoinhibition, and thus to an increased risk of damage to plant function, under conditions of low sink demand. This question clearly deserves further study.
μO-conotoxin MrVIB selectively blocks Na
v
1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits
Authors: Ekberg J. , Jayamanne A. , Vaughan C. W. , Aslan S. , Thomas L. , Mould J. , Drinkwater R. , Baker M. D. , Abrahamsen B. , Wood J. N. , Adams D. J. , Christie M. J. , Lewis R. J.
Published: November 2006

The tetrodotoxin-resistant voltage-gated sodium channel (VGSC) Na
v
1.8 is expressed predominantly by damage-sensing primary afferent nerves and is important for the development and maintenance of persistent pain states. Here we demonstrate that μO-conotoxin MrVIB from
Conus marmoreus
displays substantial selectivity for Na
v
1.8 and inhibits pain behavior in models of persistent pain. In rat sensory neurons, submicromolar concentrations of MrVIB blocked tetrodotoxin-resistant current characteristic of Na
v
1.8 but not Na
v
1.9 or tetrodotoxin-sensitive VGSC currents. MrVIB blocked human Na
v
1.8 expressed in
Xenopus
oocytes with selectivity at least 10-fold greater than other VGSCs. In neuropathic and chronic inflammatory pain models, allodynia and hyperalgesia were both reduced by intrathecal infusion of MrVIB (0.03–3 nmol), whereas motor side effects occurred only at 30-fold higher doses. In contrast, the nonselective VGSC blocker lignocaine displayed no selectivity for allodynia and hyperalgesia versus motor side effects. The actions of MrVIB reveal that VGSC antagonists displaying selectivity toward Na
v
1.8 can alleviate chronic pain behavior with a greater therapeutic index than nonselective antagonists.
Akt1 deficiency affects neuronal morphology and predisposes to abnormalities in prefrontal cortex functioning
Authors: Lai Wen-Sung , Xu Bin , Westphal Koen G. C. , Paterlini Marta , Olivier Berend , Pavlidis Paul , Karayiorgou Maria , Gogos Joseph A.
Published: November 2006

There is accumulating evidence that AKT signaling plays a role in the pathogenesis of schizophrenia. We asked whether
Akt1
deficiency in mice results in structural and functional abnormalities in prefrontal cortex (PFC). Exploratory transcriptional profiling revealed concerted alterations in the expression of PFC genes controlling synaptic function, neuronal development, myelination, and actin polymerization, and follow-up ultrastructural analysis identified consistent changes in the dendritic architecture of pyramidal neurons. Behavioral analysis indicated that
Akt1
-mutant mice have normal acquisition of a PFC-dependent cognitive task but abnormal working memory retention under neurochemical challenge of three distinct neurotransmitter systems. Thus,
Akt1
deficiency creates a context permissive for gene–gene and gene–environment interactions that modulate PFC functioning and contribute to the disease risk associated with this locus, the severity of the clinical syndrome, or both.
Evaluating alternative hypotheses for the early evolution and diversification of ants
Authors: Brady Seán G. , Schultz Ted R. , Fisher Brian L. , Ward Philip S.
Published: November 2006

Ants are the world's most diverse and ecologically dominant eusocial organisms. Resolving the phylogeny and timescale for major ant lineages is vital to understanding how they achieved this success. Morphological, molecular, and paleontological studies, however, have presented conflicting views on early ant evolution. To address these issues, we generated the largest ant molecular phylogenetic data set published to date, containing ≈6 kb of DNA sequence from 162 species representing all 20 ant subfamilies and 10 aculeate outgroup families. When these data were analyzed with and without outgroups, which are all distantly related to ants and hence long-branched, we obtained conflicting ingroup topologies for some early ant lineages. This result casts strong doubt on the existence of a poneroid clade as currently defined. We compare alternate attachments of the outgroups to the ingroup tree by using likelihood tests, and find that several alternative rootings cannot be rejected by the data. These alternatives imply fundamentally different scenarios for the early evolution of ant morphology and behavior. Our data strongly support several notable relationships within the more derived formicoid ants, including placement of the enigmatic subfamily Aenictogitoninae as sister to
Dorylus
army ants. We use the molecular data to estimate divergence times, employing a strategy distinct from previous work by incorporating the extensive fossil record of other aculeate Hymenoptera as well as that of ants. Our age estimates for the most recent common ancestor of extant ants range from ≈115 to 135 million years ago, indicating that a Jurassic origin is highly unlikely.
Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph
+
leukemia in mice
Authors: Hu Yiguo , Swerdlow Sarah , Duffy Theodore M. , Weinmann Roberto , Lee Francis Y. , Li Shaoguang
Published: November 2006

It is generally believed that shutting down the kinase activity of BCR-ABL by imatinib will completely inhibit its functions, leading to inactivation of its downstream signaling pathways and cure of the disease. Imatinib is highly effective at treating human Philadelphia chromosome-positive (Ph
+
) chronic myeloid leukemia (CML) in chronic phase but not Ph
+
B cell acute lymphoblastic leukemia (B-ALL) and CML blast crisis. We find that SRC kinases activated by BCR-ABL remain fully active in imatinib-treated mouse leukemic cells, suggesting that imatinib does not inactivate all BCR-ABL-activated signaling pathways. This SRC pathway is essential for leukemic cells to survive imatinib treatment and for CML transition to lymphoid blast crisis. Inhibition of both SRC and BCR-ABL kinase activities by dasatinib affords complete B-ALL remission. However, curing B-ALL and CML mice requires killing leukemic stem cells insensitive to both imatinib and dasatinib. Besides BCR-ABL and SRC kinases, stem cell pathways must be targeted for curative therapy of Ph
+
leukemia.
Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels
Authors: Huber Tobias B. , Schermer Bernhard , Müller Roman Ulrich , Höhne Martin , Bartram Malte , Calixto Andrea , Hagmann Henning , Reinhardt Christian , Koos Fabienne , Kunzelmann Karl , Shirokova Elena , Krautwurst Dietmar , Harteneck Christian , Simons Matias , Pavenstädt Hermann , Kerjaschki Dontscho , Thiele Christoph , Walz Gerd , Chalfie Martin , Benzing Thomas
Published: November 2006

The prohibitin (PHB)-domain proteins are membrane proteins that regulate a variety of biological activities, including mechanosensation, osmotic homeostasis, and cell signaling, although the mechanism of this regulation is unknown. We have studied two members of this large protein family, MEC-2, which is needed for touch sensitivity in
Caenorhabditis elegans
, and Podocin, a protein involved in the function of the filtration barrier in the mammalian kidney, and find that both proteins bind cholesterol. This binding requires the PHB domain (including palmitoylation sites within it) and part of the N-terminally adjacent hydrophobic domain that attaches the proteins to the inner leaflet of the plasma membrane. By binding to MEC-2 and Podocin, cholesterol associates with ion-channel complexes to which these proteins bind: DEG/ENaC channels for MEC-2 and TRPC channels for Podocin. Both the MEC-2-dependent activation of mechanosensation and the Podocin-dependent activation of TRPC channels require cholesterol. Thus, MEC-2, Podocin, and probably many other PHB-domain proteins by binding to themselves, cholesterol, and target proteins regulate the formation and function of large protein–cholesterol supercomplexes in the plasma membrane.
Implications of the quaternary twist allosteric model for the physiology and pathology of nicotinic acetylcholine receptors
Authors: Taly Antoine , Corringer Pierre-Jean , Grutter Thomas , de Carvalho Lia Prado , Karplus Martin , Changeux Jean-Pierre
Published: November 2006

Nicotinic acetylcholine receptors (nAChR) are pentameric ligand-gated ion channels composed of subunits that consist of an extracellular domain that carries the ligand-binding site and a distinct ion-pore domain. Signal transduction results from the allosteric coupling between the two domains: the distance from the binding site to the gate of the pore domain is 50 Å. Normal mode analysis with a C
α
Gaussian network of a new structural model of the neuronal α7 nAChR showed that the lowest mode involves a global quaternary twist motion that opens the ion pore. A molecular probe analysis, in which the network is modified at each individual amino acid residue, demonstrated that the major effect is to change the frequency, but not the form, of the twist mode. The largest effects were observed for the ligand-binding site and the Cys-loop. Most (24/27) of spontaneous mutations known to cause congenital myasthenia and autosomal dominant nocturnal frontal lobe epilepsy are located either at the interface between subunits or, within a given subunit, at the interface between rigid blocks. These interfaces are modified significantly by the twist mode. The present analysis, thus, supports the quaternary twist model of the nAChR allosteric transition and provides a qualitative interpretation of the effect of the mutations responsible for several receptor pathologies.
Cognitive cladistics and cultural override in Hominid spatial cognition
Authors: Haun Daniel B. M. , Rapold Christian J. , Call Josep , Janzen Gabriele , Levinson Stephen C.
Published: November 2006

Current approaches to human cognition often take a strong nativist stance based on Western adult performance, backed up where possible by neonate and infant research and almost never by comparative research across the Hominidae. Recent research suggests considerable cross-cultural differences in cognitive strategies, including relational thinking, a domain where infant research is impossible because of lack of cognitive maturation. Here, we apply the same paradigm across children and adults of different cultures and across all nonhuman great ape genera. We find that both child and adult spatial cognition systematically varies with language and culture but that, nevertheless, there is a clear inherited bias for one spatial strategy in the great apes. It is reasonable to conclude, we argue, that language and culture mask the native tendencies in our species. This cladistic approach suggests that the correct perspective on human cognition is neither nativist uniformitarian nor “blank slate” but recognizes the powerful impact that language and culture can have on our shared primate cognitive biases.
uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues
Authors: Meng Songdong , Tripathy Debu , Shete Sanjay , Ashfaq Raheela , Saboorian Hossein , Haley Barbara , Frenkel Eugene , Euhus David , Leitch Marilyn , Osborne Cynthia , Clifford Edward , Perkins Steve , Beitsch Peter , Khan Amanullah , Morrison Larry , Herlyn Dorothee , Terstappen Leon W. M. M. , Lane Nancy , Wang Jianqiang , Uhr Jonathan
Published: November 2006

Overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis. HER-2 overexpression is caused by HER-2 gene amplification. The anti-HER-2 antibody trastuzumab significantly improves clinical outcome for HER2-positive breast cancer. Drugs that target the uPA system are in early clinical trials. The aims of this study were to determine whether urokinase plasminogen activator receptor (uPAR) gene amplification occurs and whether analysis of individual tumor cells (TCs) in the blood or tissue can add information to conventional pathological analysis that could help in diagnosis and treatment. Analysis of individual TCs indicates that uPAR amplification occurs in a significant portion of primary breast cancers and also circulating tumor cells (CTCs) from patients with advanced disease. There was complete concordance between touch preps (TPs) and conventional pathological examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and CTCs provided that acquisition of HER-2 gene amplification in CTCs was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same TC and patient, suggesting a biological bias and potential advantage for coamplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100 and 92% of patients, respectively.
Predictive Value of Lymph Node Metastases and Extracapsular Extension for the Risk of Distant Metastases in Laryngeal Carcinoma
Authors: Oosterkamp Stephanie , de Jong Jos M. A. , Van Den Ende Piet L. , Manni Johannes J. , Dehing‐Oberije Cary , Kremer Bernd
Published: November 2006

Objective: The objective of this retrospective chart analysis was to determine the prognostic value of the lymph node status and extracapsular lymph node extension (ECE) of the neck for the development of distant metastases in squamous cell carcinoma of the larynx.

Methods: One hundred sixty‐five patients treated for laryngeal carcinoma with a neck dissection with histologic evaluation were included. Primary study end point was distant metastasis‐free survival. Univariate analysis with the Kaplan‐Meier method was used to calculate distant metastasis‐free survival and overall survival for the whole group and for groups according to ECE/lymph node status. Patients were classified as 1) no metastatic lymph nodes, 2) metastatic lymph nodes without ECE, or 3) metastatic lymph nodes with ECE. Univariate Cox regression was performed with outcome distant metastasis‐free survival.

Results: The median overall survival for the whole group was 5.1 years and the 5‐year survival rate was 51%. The median distant metastasis‐free survival for the whole group could not be calculated and the 5‐year metastasis‐free survival rate was 78%. The hazard ratio was 3.4 (95% confidence interval [CI] = 1.0–12.1) for patients with positive nodes and without ECE and 10.5 (95% CI = 3.6–30.8) for the patients with metastatic nodes and with ECE compared with the patients without metastatic lymph nodes.

Conclusion: The presence of ECE in metastatic lymph nodes augments the risk of distant metastasis by nine times in laryngeal carcinoma. Metastatic lymph nodes without ECE show a risk three times greater.
The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster
Authors: van Rij Ronald P. , Saleh Maria-Carla , Berry Bassam , Foo Catherine , Houk Andrew , Antoniewski Christophe , Andino Raul
Published: November 2006

Most organisms have evolved defense mechanisms to protect themselves from viruses and other pathogens. Arthropods lack the protein-based adaptive immune response found in vertebrates. Here we show that the central catalytic component of the RNA-induced silencing complex (RISC), the nuclease Argonaute 2 (Ago-2), is essential for antiviral defense in adult Drosophila melanogaster. Ago-2-defective flies are hypersensitive to infection with a major fruit fly pathogen, Drosophila C virus (DCV), and with Cricket Paralysis virus (CrPV). Increased mortality in ago-2 mutant flies was associated with a dramatic increase in viral RNA accumulation and virus titers. The physiological significance of this antiviral mechanism is underscored by our finding that DCV encodes a potent suppressor of RNA interference (RNAi). This suppressor binds long double-stranded RNA (dsRNA) and inhibits Dicer-2-mediated processing of dsRNA into short interfering RNA (siRNA), but does not bind short siRNAs or disrupt the microRNA (miRNA) pathway. Based on these results we propose that RNAi is a major antiviral immune defense mechanism in Drosophila.
The phytotoxin coronatine from Pseudomonas syringae pv. tomato DC3000 functions as a virulence factor and influences defence pathways in edible brassicas
Authors: ELIZABETH SARITA V. , BENDER CAROL L.
Published: November 2006

The phytotoxin coronatine (COR) contributes to the virulence of Pseudomonas syringae pv. tomato (Pst) strain DC3000 on Arabidopsis thaliana and tomato. However, little is known regarding the role of COR in the virulence of DC3000 on cultivated Brassica spp. In this study, the role of COR and its precursors, coronafacic acid (CFA) and coronamic acid (CMA), were examined in the virulence of Pst DC3000 on collard and turnip, two important edible brassicas. Pst DC3000 and three well‐defined COR− biosynthetic mutants of DC3000 exhibited substantial differences in the timing and phenotype of disease lesions on collard and turnip. When examined 3 days post‐inoculation (dpi), collard inoculated with DC3000 exhibited visible anthocyanin production and lesions were chlorotic and water‐soaked. On turnip, chlorotic and necrotic lesions were evident on DC3000‐inoculated leaves 5 dpi. The bacterial population dynamics on plants inoculated with DC3000 and the COR− mutants indicated that COR was essential for DC3000 to maintain high populations in turnip, but not collard. Real‐time quantitative PCR revealed that the jasmonic acid pathway responsive genes, LOX2 and CORI1, were expressed in both hosts inoculated with Pst DC3000. PR1, a marker associated with the salicylic acid pathway, was expressed in collard and turnip inoculated with the CFA− CMA− mutant DB29, but not DC3000. Further comparison of PR1 and LOX2 expression indicated that CFA plays a subtle role in modulating defence in turnip. This is the first study to investigate the role of COR in the interaction of Pst DC3000 and cultivated brassicas using genetically and biochemically defined COR− mutants.
Phytophthora sojae: root rot pathogen of soybean and model oomycete
Authors: TYLER BRETT M.
Published: November 2006

Phytophthora sojae is an oomycete pathogen of soybean, classified in the kingdom Stramenopiles. It causes ‘damping off’ of seedlings and root rot of older plants, with an annual cost worldwide of $1–2 billion. Owing to its economic importance, this species, along with P. infestans, has been developed as a model species for the study of oomycete plant pathogens. It is readily transformed with DNA enabling over‐expression and silencing of selected genes, genetic maps have been constructed and large expressed sequence tag sequence libraries have been developed. A draft genome sequence has recently been completed. This review briefly summarizes current information about the pathogenicity, evolution, molecular biology and genomics of P. sojae.

 Taxonomy:   Phytophthora sojae (Kaufman & Gerdman): superkingdom Eukaryota; kingdom Stramenopila; phylum Oomycota; class Peronosporomycetidae; order Pythiales; family Pythiaceae; genus Phytophthora.

 Host range:   Soybean is the only economically important host. Several species of lupins have also been reported as hosts.

 Disease symptoms and signs:   All parts of the soybean plant are susceptible to infection by P. sojae, from germinating seedlings to mature plants. In the field, P. sojae causes damping off of soybean seedlings and a root and stem rot of established plants. Leaves can be infected in the field as a result of rain splash or by deliberate inoculation in the laboratory. Damping off can affect germinating seeds or emerged seedlings and is most severe when the spring is very wet and warm (25–30 °C). Established plants can become infected when the soil is wet for extended periods, especially if the soil is poorly drained. Both the cortex and the vascular tissue are colonized by P. sojae, and the infection can spread rapidly along the vascular tissues in susceptible cultivars.

 Useful websites:   http://pmgn.vbi.vt.edu, http://phytophthora.vbi.vt.edu, http://www.jgi.doe.gov/Psojae, http://www.jgi.doe.gov/Pramorum, http://www.pfgd.org, http://pamgo.vbi.vt.edu, http://soy.vbi.vt.edu, https://www.vbi.vt.edu/article/articleview/78, http://plantpath.osu.edu/faculty/dorrance.php
Carotid intima‐media thickness is increased and related to arterial stiffening in patients with beta‐thalassaemia major
Authors: Cheung Y. F. , Chow P. C. , Chan G. C. , Ha S. Y.
Published: November 2006

An increased iron store has been linked to the risk of atherosclerosis. The carotid intima‐media thickness (IMT), stiffness index, Young's elastic modulus (YEM), and augmentation index were determined in 20 patients with beta‐thalassaemia major. Compared with controls, patients had greater IMT (P < 0·001), YEM (P = 0·005), and stiffness (P = 0·009) and augmentation (P = 0·03) indices. The odds ratio for increased IMT in patients was 39. Carotid IMT correlated with YEM (P = 0·036), stiffness index (P = 0·036) and augmentation index (P = 0·006). Multivariate analysis identified patient status (P < 0·001) as the only significant determinant of IMT. These findings suggest the possibility of premature atherosclerosis in beta‐thalassaemia major patients.
Effects of phthalate esters on the sensitization phase of contact hypersensitivity induced by fluorescein isothiocyanate
Authors: Imai Y. , Kondo A. , Iizuka H. , Maruyama T. , Kurohane K.
Published: November 2006

Background
Many different types of phthalate ester are used as plasticizers and are thus found in the air. There have been several studies that suggest an association between allergies and phthalate esters. We previously found that di‐butyl phthalate (DBP) has an adjuvant effect in a mouse contact hypersensitivity model, in which fluorescein isothiocyanate (FITC) is involved as an immunogenic hapten.

Objective
We examined whether other phthalate esters enhance the process of sensitization to FITC by facilitating the trafficking of FITC‐presenting dendritic cells or macrophages from skin sites to draining lymph nodes.

Methods
Mice were epicutaneously sensitized with FITC dissolved in acetone containing a phthalate ester. Sensitization was evaluated as ear swelling after a challenge with FITC. Draining lymph node cells obtained 24 h after skin sensitization were examined for FITC fluorescence by means of flow cytometry. FITC‐positive cells were characterized with anti‐CD11c and anti‐CD11b by three‐colour flow cytometry.

Results
When mice were sensitized with FITC in acetone containing DBP or di‐n‐propyl phthalate (DPP), strong enhancement of the ear‐swelling response was observed. Di‐methyl phthalate (DMP) and di‐ethyl phthalate (DEP) were less effective but produced some enhancement. Consistent enhancement was not observed with di‐(2‐ethylhexyl) phthalate or di‐isononyl phthalate. Upon sensitization in the presence of DBP or DPP, the number of FITC‐positive dendritic cells (total CD11c+ as well as CD11c+/CD11b+) was increased in draining lymph nodes. As to the other four phthalate esters, there was no significant increase in the FITC‐positive cell number in the draining lymph nodes.

Conclusion
During the process of sensitization to FITC, DBP, and DPP exert strong adjuvant effects that are associated with enhancement of trafficking of antigen‐presenting dendritic cells from the skin to draining lymph nodes.
Interaction between variants in the interleukin‐4 receptor α and interleukin‐9 receptor genes in childhood wheezing: evidence from a birth cohort study
Authors: Melén E. , Umerkajeff S. , Nyberg F. , Zucchelli M. , Lindstedt A. , Gullstén H. , Wickman M. , Pershagen G. , Kere J.
Published: November 2006

Background
Several polymorphisms in the IL‐4 receptor α (IL4RA) gene have been associated with asthma and atopy, but with variable success in different populations. Immunologic studies suggest that IL4RA may interact with other cytokines and receptors, and gene–gene interactions have also been observed with respect to asthma. Such interactions have been proposed to explain partly the difficulties in replicating association studies.

Methods
Using the prospective birth cohort BAMSE, we examined eight single nucleotide polymorphisms (SNPs) and corresponding haplotypes in the IL4RA gene in relation to wheezing and sensitization up to age 4. We also evaluated potential interaction effects (departure from a multiplicative interaction model) between the IL4RA SNPs and four SNPs in the IL‐9 receptor (IL9R) gene previously associated with childhood wheezing.

Results
We found no main effect of the IL4RA SNPs alone and only weak associations to wheezing and sensitization when haplotypes were considered. Gene–gene interactions between several IL4RA and IL9R SNPs with regard to wheezing were observed (P=0.009), especially between IL4RA Q576R (rs1801275) and IL9R rs731476 (P=0.005). An interaction was also seen between IL4RA and IL9R haplotypes.

Conclusion
Variants in the IL4RA gene alone may not exert any major influence on susceptibility to asthma‐related diseases in childhood, but in combination with other genes, such as IL9R, IL4RA may be an important gene for disease susceptibility.
Pharmacokinetics of fentanyl delivered transdermally in healthy adult horses – variability among horses and its clinical implications
Authors: ORSINI J. A. , MOATE P. J. , KUERSTEN K. , SOMA L. R. , BOSTON R. C.
Published: November 2006

The safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60–67 μg/kg, were investigated in six healthy adult horses. Three transdermal fentanyl patches (Duragesic®), each containing 10 mg of fentanyl citrate, were applied to the mid‐dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it gradually declined in a roughly linear manner over the next 72 h. There was much individual variation, however. The initial delay ranged from 0 to 5.1 h (mean, 1.91 ± 2.0 h),Tcmaxranged from 8.5 to 14.5 h (mean, 11.4 ± 2.7 h) andCmaxranged from 0.67 to 5.12 ng/mL (mean, 2.77 ± 1.92 ng/mL). In two horses, the plasma fentanyl concentration failed to reach even 1 ng/mL, whereas in the other four horses it was >1 ng/mL for at least 40 h and for at least 72 h in two of these horses. No adverse effects attributable to fentanyl were observed in any of the horses, indicating that this dosage is safe in systemically healthy adult horses. However, it failed to achieve plasma fentanyl concentrations generally considered to be analgesic (≥1 ng/mL) in about one‐third of horses.
Metabolism of isometamidium in hepatocytes isolated from control and inducer‐treated rats
Authors: BOIBESSOT I. , TETTEY J. N. A. , SKELLERN G. G. , WATSON D. G. , GRANT M. H.
Published: November 2006

Little is known about the metabolism and mechanism of action of the trypanocide, isometamidium (ISM), the major drug used for prophylaxis of trypanosomiasis. We have investigated its metabolism and distribution in isolated rat hepatocytes using liquid chromatography‐mass spectrometry and confocal laser scanning microscopy (CLSM). Two putative metabolites were formed, which were proposed to be a mono‐acetyl derivative and an oxidized metabolite (SII). This is the first demonstration of the hepatic metabolism of ISM, as previous in vivo studies were hampered by dose‐limiting toxicity and insensitive analytical methods. The intrinsic fluorescence of the drug enabled its intracellular uptake to be followed by CLSM. It is taken up rapidly into the nucleolus, nuclear membrane and endoplasmic reticulum within 5 min, and retained in the nucleus for at least 24 h. Persistent binding of ISM to cellular macromolecules may contribute to its prophylactic effect in vivo. Pretreatment of rats with 3‐methylcholanthrene, phenobarbitone (PB) or the widely used pyrethroid pesticide, deltamethrin, resulted in an increase in metabolism of ISM to the proposed SII after 1 h incubation with hepatocytes. 3‐methylcholanthrene was the most potent inducer, causing a maximal 19.5‐fold induction of SII formation after exposure of hepatocytes to ISM for 1 h compared with formation by control hepatocytes. In comparison, at the 1 h timepoint deltamethrin pre‐treatment caused a 10.2‐fold induction, and PB only 8.2 fold.
Herbivory mitigation through increased water‐use efficiency in a leaf‐mining moth–apple tree relationship
Authors: PINCEBOURDE SYLVAIN , FRAK ELA , SINOQUET HERVÉ , REGNARD JEAN LUC , CASAS JÉRÔME
Published: November 2006

Herbivory alters plant gas exchange but the effects depend on the type of leaf damage. In contrast to ectophagous insects, leaf miners, by living inside the leaf tissues, do not affect the integrity of the leaf surface. Thus, the effect of leaf miners on CO2 uptake and water‐use efficiency by leaves remains unclear. We explored the impacts of the leaf‐mining moth Phyllonorycter blancardella (Lepidoptera: Gracillariidae) on light responses of the apple leaf gas exchanges to determine the balance between the negative effects of reduced photosynthesis and potential positive impacts of increased water‐use efficiency (WUE). Gas exchange in intact and mined leaf tissues was measured using an infrared gas analyser. The maximal assimilation rate was slightly reduced but the light response of net photosynthesis was not affected in mined leaf tissues. The transpiration rate was far more affected than the assimilation rate in the mine integument as a result of stomatal closure from moderate to high irradiance level. The WUE was about 200% higher in the mined leaf tissues than in intact leaf portions. Our results illustrate a novel mechanism by which plants might minimize losses from herbivore attacks; via trade‐offs between the negative impacts on photosynthesis and the positive effects of increased WUE.
Protochlorophyllide and POR development in dark‐grown plants with different proportions of short‐wavelength and long‐wavelength protochlorophyllide spectral forms†
Authors: Amirjani Mohammad R. , Sundqvist Krystyna , Sundqvist Christer
Published: November 2006

The effect of leaf developmental age on the protochlorophyllide (Pchlide) spectral forms and the expression of messenger RNA (mRNA) encoding NADPH‐protochlorophyllide oxidoreductase (POR) were investigated. Four plant species, maize, wheat, pea and the lip1 mutant of pea, known to have different composition of the spectral forms of Pchlide, were used. In very young plants short‐wavelength Pchlide with a fluorescence emission at 631 nm was dominating. Long‐wavelength Pchlide fluorescing mainly around 655 nm increased during development, which led to a relative decrease of the short‐wavelength forms. During ageing of the leaves, the short‐wavelength forms slightly increased again. The different proportions of short‐ and long‐wavelength Pchlide spectral forms were, however, found to vary with the developmental stage in a species specific pattern. The steady‐state level of POR mRNA and the amount of the POR protein were similar in species dominated by short‐wavelength forms and in species dominated with long‐wavelength forms. Even if POR is necessary for the formation of the long‐wavelength Pchlide form it is not the only limiting factor for formation of long‐wavelength Pchlide forms in mature plants.
On the phylogeny, expression and targeting of plant nucleoside diphosphate kinases
Authors: Hammargren Jenni , Sundström Jens , Johansson Monika , Bergman Per , Knorpp Carina
Published: November 2006

The plant nucleoside diphosphate kinase (NDPK, EC 2.7.4.6) gene family consists of three groups whose gene products are found in different subcellular locations. In this study we discuss the evolutionary history, localization and expression of the NDPK genes, addressing the question of functional specialization of the different NDPKs. A phylogenetic analysis revealed that the three NDPK isoforms were present already in the last common ancestor of vascular plants and mosses. Our data also imply that the NDPK3 genes possess a higher degree of conservation than the NDPK1 and NDPK2 genes. The expression levels of the different NDPKs in Arabidopsis thaliana inflorescences, leaves and roots were evaluated using quantitative PCR as well as in silico methods. This analysis showed that NDPK1 is the most highly expressed NDPK gene in all the studied tissues. NDPK3a has the second highest NDPK expression, while NDPK3b is expressed to a very low extent. However, expression of NDPK3b is elevated in inflorescence tissue. In situ hybridization experiments performed on inflorescences showed NDPK3a expression in actively dividing cells. NDPK3b expression was observed during later stages of flower development, specifically in the tapetum, ovules and petals. Additionally, we show that an NDPK3 protein is able to direct the green fluorescent protein to both mitochondria and chloroplasts using transient expression in leaf protoplasts. The dual localisation of NDPK3 was confirmed by Western blot, which also demonstrated that the majority of the NDPK3 protein is found in the mitochondria.
Maize Sh2 gene is constrained by natural selection but escaped domestication
Authors: MANICACCI D. , FALQUE M. , LE GUILLOU S. , PIÉGU B. , HENRY A.‐M. , LE GUILLOUX M. , DAMERVAL C. , DE VIENNE D.
Published: November 2006

In Zea mays L., we studied the molecular evolution of Shrunken2 (Sh2), a gene that encodes the large subunits of a major enzyme in endosperm starch biosynthesis, ADP‐glucose pyrophosphorylase. We compared 4669 bp of the Sh2 coding region on 50 accessions of maize and teosinte. Very few nucleotide polymorphisms were found when compared with other genes in Z. mays, revealing an effect of purifying selection in the whole species that predates domestication. Additionally, the comparison of Sh2 sequences in all Z. mays subspecies and outgroups Z. diploperennis and Tripsacum dactyloides suggests the occurrence of an ancient selective sweep in the Sh2 3′ region. The amount and nature of nucleotide diversity are similar in both maize and teosinte, confirming previous results that suggested that Sh2 has not been involved in maize domestication. The very low level of nucleotide diversity as well as the highly conserved protein sequence suggest that natural selection retained effective Sh2 allele(s) long before agriculture started, making human selection inefficient on this gene.
Alternative measures of response to Pseudomonas aeruginosa infection in Drosophila melanogaster
Authors: CORBY‐HARRIS V. , HABEL K. E. , ALI F. G. , PROMISLOW D. E. L.
Published: November 2006

Studies of invertebrate immune defence often measure genetic variation either for the fitness cost of infection or for the ability of the host to clear the parasite. These studies assume that variation in measures of resistance is related to variation in fitness costs of infection. To test this assumption, we infected strains of the fruit fly, Drosophila melanogaster, with a pathogenic bacterium. We then measured the correlation between host bacterial load and the ability to survive infection. Despite the presence of genotypic variation for both traits, bacterial load and survival post‐infection were not correlated. Our results support previous arguments that individual measures of immune function and the host's ability to survive infection may be decoupled. In light of these results, we suggest that the difference between tolerance and resistance to infection, a distinction commonly found in the plant literature, may also be of value in studies of invertebrate immunity.
Nurse prescribing in low‐resource settings: professional considerations
Authors: Miles K. , Seitio O. , McGilvray M.
Published: November 2006

Aim:  This paper reviews the professional issues relating to nurse prescribing in low‐resource countries.

Background:  In order to meet community healthcare need, nurses in low‐resource settings often perform roles such as prescribing medication, for which they may not have had adequate training, often in the absence of supervision, legislation and regulation. In general, however, there is a paucity of published evidence relating to nurse prescribing in low‐resource settings. Several studies have demonstrated improved health and social outcomes resulting from nurse‐prescribing interventions. Alternatively, other studies have shown unsatisfactory nurse‐prescribing patterns, such as overuse of antibiotics and poor adherence to national treatment guidelines. There are several examples of how nurse prescribing in low‐resource countries has been recognized and addressed at national level; these are discussed in detail. However, given that it is widely acknowledged how crucial nurses are for the delivery of health care in regions where there are no medical personnel, international policy and guidance relating to this issue is only just beginning to acknowledge and address the relevant issues.

Conclusion:  Where there is a need for nurses to extend their role in the ordering of medicines and other treatments, the responsibilities, training, rights and roles of these nurses need to be clearly defined and recognized at all levels of the health service. There is a need for rigorous evaluations incorporating health, social and economic outcomes of nurse‐prescribing interventions, in addition to close monitoring of legislative and regulatory changes related to nursing roles.
Applying to the European Research Area Network Scheme (ERA‐NET): collaborative working for nursing and midwifery research*
Authors: Condell S. L. , Fyffe T. , Moreno‐Casbas T. , Poortvliet P. , Wilkinson J. , Egea‐Zerolo B. , Jones C.
Published: November 2006

Aim:  This paper reports on work undertaken to achieve an application for monies from the European Commission’s 6th Framework Programme by some key stakeholders, working with a nursing and midwifery research agenda at national policy levels.

Background:  A short outline of the European Commission’s European Research Area Network scheme is given in order to set the paper in context, and the vision underpinning the application is discussed.

Conclusion:  The paper describes the processes that were undertaken to bring to fruition such collaborative work, and some key lessons are outlined. Seeking opportunities to enhance nursing and midwifery research within a European context gives value to the application, which was ultimately successful.
Gender differs: Modelling knowledge sharing from a perspective of social network ties
Authors: Lin Chieh‐Peng
Published: November 2006

The present paper proposes a model of knowledge sharing, in which coworker congruence, outcome interdependence, perceived organizational support, and procedural justice influence knowledge sharing indirectly through the mediation of instrumental ties and expressive ties, and examined gender differences in causal connections within the model. In a sample of employees in Taiwan, it was shown that the influence of instrumental ties on knowledge sharing is stronger for females than for males; the influence of expressive ties on knowledge sharing is stronger for males than for females; the influence of coworker congruence on expressive ties is stronger for females than for males; the influence of outcome interdependence on instrumental ties is stronger for females than for males; and the influence of perceived organizational support on instrumental ties is stronger for males than for females.
Constant market shares analysis: uses, limitations and prospects*
Authors: Ahmadi‐Esfahani Fredoun Z.
Published: November 2006

In this paper, we generalise the constant market shares (CMS) framework, with particular attention to the underlying theoretical conditions required for diagnostic interpretation. The approach is applied to the analysis of the export performance of the Australian processed food sector in South‐East Asia over the period 1980–2003. We conclude that the usefulness of CMS analysis for evaluating a country's international trade performance depends upon the empirical validity of the aggregation assumptions implicit in the diagnostic interpretation.
Low‐inflation Targeting and Long‐run Unemployment*
Authors: Lundborg Per , Sacklén Hans
Published: November 2006

The model of Akerlof, Dickens and Perry (2000) (ADP) predicts that low inflation may cause unemployment to persist at high levels. When applied to U.S. data, their results strongly rejected the conventional NAIRU model. We apply the ADP model to Swedish data. The fact that our Swedish data also reject the NAIRU model has a number of interesting implications for the Swedish economy and, potentially, for other European countries as well. The results indicate that raising the Swedish inflation target from 2 to 4 percent would bring long‐run unemployment down by several percentage points. The possibility of ADP‐type long‐run Phillips curves also across the euro countries may raise some concern about the EMU project. While detailed studies on other countries are needed, there is nothing to suggest that these non‐vertical Phillips curves would not differ considerably across the euro countries. Any single inflation level targeted by the ECB would then generate excess unemployment in individual member states.
A Union‐bashing Model of Inflation Targeting
Authors: Meland Frode
Published: November 2006

This paper shows that in an open two‐sector economy, centralization of wage setting may be important in determining the employment (and welfare) effects of different monetary targets. By disciplining unions in the sectors open to international trade, exchange rate targeting yields higher employment than inflation targeting when wage‐setting is more centralized in the open sector than in the shielded sector. When wage‐setting centralization is higher in the shielded sector, we show that general price‐level inflation targeting, while better than exchange rate targeting, is inferior to an inflation target that focuses more heavily on shielded sector prices.
Mainstreaming Equality: Implications of the Provision of Support at Home for Majority and Minority Ethnic Older People
Authors: Bowes Alison
Published: November 2006

This paper explores the potential impact and practical difficulties of mainstreaming equalities in support at home for minority and majority ethnic older people, drawing on two linked empirical research projects. Social care providers have long faced difficulties in catering for diversity of need. Recently, diversity within minority ethnic groups has increased, and there is now a statutory duty to promote equality. Research findings illustrate the complexity of exclusionary processes, with particular reference to the example of health care. There is a gap between the high‐level commitment to mainstreaming equality and people's lived experiences. Autonomy and choice are central to community care legislation, policy and practice guidance, but in reality, the research shows that choices are limited for both minority and majority older people. More user‐focused approaches and grassroots involvement may offer ways forward, despite some limitations of current models. In conclusion, the potentiality of a broad mainstreaming equality perspective is highlighted, but challenges include a need for a more grounded approach, better engagement with user groups and a need to focus on understanding issues of implementation.
‘All My Worldly Goods I Share with you’? Managing Money at the Transition to Heterosexual Marriage
Authors: Burgoyne Carole B. , Clarke Victoria , Reibstein Janet , Edmunds Anne
Published: November 2006

Studies in the 1980s and 1990s revealed that financial arrangements in marriage tended to disadvantage women, especially those with young children. However, much of that research focused upon relatively well-established married (or remarried) couples, and we have little insight into the choices that today's newly-weds are making, or what influences their choices. To address this gap in our understanding, in-depth, semi-structured interviews were conducted with forty-two heterosexual couples on the brink of their first marriage. We explored their monetary practices and the way that they thought about money in the relationship. The results of a grounded theory analysis showed that six couples were pooling all or most of their money, fifteen were using a partial-pooling system, twenty were using an independent management system (with separate accounts), and one couple had an arrangement where all the money was controlled and managed by one partner. A key factor was perceived ownership of money, and this influenced the extent to which finances were being merged and treated as a collective resource. Other factors included the couple's current living arrangements and beliefs about the importance of sharing and independence within the relationship.