bluuebunny/crossref_metadata_2025 huggingface dataset:
PsbP Protein, But Not PsbQ Protein, Is Essential for the Regulation and Stabilization of Photosystem II in Higher Plants
Authors: Ifuku Kentaro , Yamamoto Yumiko , Ono Taka-aki , Ishihara Seiko , Sato Fumihiko
Published: October 2005

PsbP and PsbQ proteins are extrinsic subunits of photosystem II (PSII) and participate in the normal function of photosynthetic water oxidation. Both proteins exist in a broad range of the oxygenic photosynthetic organisms; however, their physiological roles in vivo have not been well defined in higher plants. In this study, we established and analyzed transgenic tobacco (Nicotiana tabacum) plants in which the levels of PsbP or PsbQ were severely down-regulated by the RNA interference technique. A plant that lacked PsbQ showed no specific phenotype compared to a wild-type plant. This suggests that PsbQ in higher plants is dispensable under the normal growth condition. On the other hand, a plant that lacked PsbP showed prominent phenotypes: drastic retardation of growth, pale-green-colored leaves, and a marked decrease in the quantum yield of PSII evaluated by chlorophyll fluorescence. In PsbP-deficient plant, most PSII core subunits were accumulated in thylakoids, whereas PsbQ, which requires PsbP to bind PSII in vitro, was dramatically decreased. PSII without PsbP was hypersensitive to light and rapidly inactivated when the repair process of the damaged PSII was inhibited by chloramphenicol. Furthermore, thermoluminescence studies showed that the catalytic manganese cluster in PsbP-deficient leaves was markedly unstable and readily disassembled in the dark. The present results demonstrated that PsbP, but not PsbQ, is indispensable for the normal PSII function in higher plants in vivo.
Overexpression of AtCpNifS Enhances Selenium Tolerance and Accumulation in Arabidopsis
Authors: Van Hoewyk Douglas , Garifullina Gulnara F. , Ackley Ashley R. , Abdel-Ghany Salah E. , Marcus Matthew A. , Fakra Sirine , Ishiyama Keiki , Inoue Eri , Pilon Marinus , Takahashi Hideki , Pilon-Smits Elizabeth A.H.
Published: October 2005

Selenium (Se) is an essential element for many organisms but is toxic at higher levels. CpNifS is a chloroplastic NifS-like protein in Arabidopsis (Arabidopsis thaliana) that can catalyze the conversion of cysteine into alanine and elemental sulfur (S0) and of selenocysteine into alanine and elemental Se (Se0). We overexpressed CpNifS to investigate the effects on Se metabolism in plants. CpNifS overexpression significantly enhanced selenate tolerance (1.9-fold) and Se accumulation (2.2-fold). CpNifS overexpressors showed significantly reduced Se incorporation into protein, which may explain their higher Se tolerance. Also, sulfur accumulation was enhanced by approximately 30% in CpNifS overexpressors, both on media with and without selenate. Root transcriptome changes in response to selenate mimicked the effects observed under sulfur starvation. There were only a few transcriptome differences between CpNifS-overexpressing plants and wild type, besides the 25- to 40-fold increase in CpNifS levels. Judged from x-ray analysis of near edge spectrum, both CpNifS overexpressors and wild type accumulated mostly selenate (SeVI). In conclusion, overexpression of this plant NifS-like protein had a pronounced effect on plant Se metabolism. The observed enhanced Se accumulation and tolerance of CpNifS overexpressors show promise for use in phytoremediation.
Plant-Derived Transfer DNAs
Authors: Rommens Caius M. , Bougri Oleg , Yan Hua , Humara Jaime M. , Owen Joanna , Swords Kathy , Ye Jingsong
Published: October 2005

The transfer of DNA from Agrobacterium to plant cell nuclei is initiated by a cleavage reaction within the 25-bp right border of Ti plasmids. In an effort to develop all-native DNA transformation vectors, 50 putative right border alternatives were identified in both plant expressed sequence tags and genomic DNA. Efficacy tests in a tobacco (Nicotiana tabacum) model system demonstrated that 14 of these elements displayed at least 50% of the activity of conventional Agrobacterium transfer DNA borders. Four of the most effective plant-derived right border alternatives were found to be associated with intron-exon junctions. Additional elements were embedded within introns, exons, untranslated trailers, and intergenic DNA. Based on the identification of a single right border alternative in Arabidopsis and three in rice (Oryza sativa), the occurrence of this motif was estimated at a frequency of at least 0.8×10−8. Modification of plasmid DNA sequences flanking the alternative borders demonstrated that both upstream and downstream sequences play an important role in initiating DNA transfer. Optimal DNA transfer required the elements to be preceded by pyrimidine residues interspaced by AC-rich trinucleotides. Alteration of this organization lowered transformation frequencies by 46% to 93%. Despite their weaker resemblance with left borders, right border alternatives also functioned effectively in terminating DNA transfer, if both associated with an upstream A[C/T]T[C/G]A[A/T]T[G/T][C/T][G/T][C/G]A[C/T][C/T][A/T] domain and tightly linked cytosine clusters at their junctions with downstream DNA. New insights in border region requirements were used to construct an all-native alfalfa (Medicago sativa) transfer DNA vector that can be used for the production of intragenic plants.
Identification of Three Urease Accessory Proteins That Are Required for Urease Activation in Arabidopsis
Authors: Witte Claus-Peter , Rosso Mario G. , Romeis Tina
Published: October 2005

Urease is a nickel-containing urea hydrolase involved in nitrogen recycling from ureide, purine, and arginine catabolism in plants. The process of urease activation by incorporation of nickel into the active site is a prime example of chaperone-mediated metal transfer to an enzyme. Four urease accessory proteins are required for activation in Klebsiella aerogenes. In plants urease accessory proteins have so far been only partially defined. Using reverse genetic tools we identified four genes that are necessary for urease activity in Arabidopsis (Arabidopsis thaliana; ecotypes Columbia and Nössen). Plants bearing T-DNA or Ds element insertions in either the structural gene for urease or in any of the three putative urease accessory genes AtureD, AtureF, and AtureG lacked the corresponding mRNAs and were defective in urease activity. In contrast to wild-type plants, the mutant lines were not able to support growth with urea as the sole nitrogen source. To investigate whether the identified accessory proteins would be sufficient to support eukaryotic urease activation, the corresponding cDNAs were introduced into urease-negative Escherichia coli. In these bacteria, urease activity was observed only when all three plant accessory genes were coexpressed together with the plant urease gene. Remarkably, plant urease activation occurred as well in cell-free E. coli extracts, but only in extracts from cells that had expressed all three accessory proteins. The future molecular dissection of the plant urease activation process may therefore be performed in vitro, providing a powerful tool to further our understanding of the biochemistry of chaperone-mediated metal transfer processes in plants.
Maize rough sheath2 and ItsArabidopsisOrthologue ASYMMETRIC LEAVES1 Interact with HIRA, a Predicted Histone Chaperone, to MaintainknoxGene Silencing and Determinacy during Organogenesis
Authors: Phelps-Durr Tara L. , Thomas Julie , Vahab Phil , Timmermans Marja C.P.
Published: October 2005

Plant shoots are characterized by indeterminate growth resulting from the action of a population of stem cells in the shoot apical meristem (SAM). Indeterminacy within the SAM is specified in part by the class I knox homeobox genes. The myb domain proteins rough sheath2 (RS2) and ASYMMETRIC LEAVES1 (AS1) from maize (Zea mays) and Arabidopsis thaliana, respectively, are required to establish determinacy during leaf development. These proteins are part of a cellular memory system that in response to a stem cell–derived signal keeps knox genes in an off state during organogenesis. Here, we show that RS2/AS1 can form conserved protein complexes through interaction with the DNA binding factor ASYMMETRIC LEAVES2, a predicted RNA binding protein (RIK, for RS2-Interacting KH protein), and a homologue of the chromatin-remodeling protein HIRA. Partial loss of HIRA function in Arabidopsis results in developmental defects comparable to those of as1 and causes reactivation of knox genes in developing leaves, demonstrating a direct role for HIRA in knox gene repression and the establishment of determinacy during leaf formation. Our data suggest that RS2/AS1 and HIRA mediate the epigenetic silencing of knox genes, possibly by modulating chromatin structure. Components of this process are conserved in animals, suggesting the possibility that a similar epigenetic mechanism maintains determinacy during both plant and animal development.
Cell Cycle Progression in the Pericycle Is Not Sufficient for SOLITARY ROOT/IAA14-Mediated Lateral Root Initiation inArabidopsis thaliana
Authors: Vanneste Steffen , De Rybel Bert , Beemster Gerrit T.S. , Ljung Karin , De Smet Ive , Van Isterdael Gert , Naudts Mirande , Iida Ryusuke , Gruissem Wilhelm , Tasaka Masao , Inzé Dirk , Fukaki Hidehiro , Beeckman Tom
Published: October 2005

To study the mechanisms behind auxin-induced cell division, lateral root initiation was used as a model system. By means of microarray analysis, genome-wide transcriptional changes were monitored during the early steps of lateral root initiation. Inclusion of the dominant auxin signaling mutant solitary root1 (slr1) identified genes involved in lateral root initiation that act downstream of the auxin/indole-3-acetic acid (AUX/IAA) signaling pathway. Interestingly, key components of the cell cycle machinery were strongly defective in slr1, suggesting a direct link between AUX/IAA signaling and core cell cycle regulation. However, induction of the cell cycle in the mutant background by overexpression of the D-type cyclin (CYCD3;1) was able to trigger complete rounds of cell division in the pericycle that did not result in lateral root formation. Therefore, lateral root initiation can only take place when cell cycle activation is accompanied by cell fate respecification of pericycle cells. The microarray data also yielded evidence for the existence of both negative and positive feedback mechanisms that regulate auxin homeostasis and signal transduction in the pericycle, thereby fine-tuning the process of lateral root initiation.
Solution structure of Archaeglobus fulgidis peptidyl‐tRNA hydrolase (Pth2) provides evidence for an extensive conserved family of Pth2 enzymes in archea, bacteria, and eukaryotes
Authors: Powers Robert , Mirkovic Nebojsa , Goldsmith‐Fischman Sharon , Acton Thomas B. , Chiang Yiwen , Huang Yuanpeng J. , Ma Lichung , Rajan P.K. , Cort John R. , Kennedy Michael A. , Liu Jinfeng , Rost Burkhard , Honig Barry , Murray Diana , Montelione Gaetano T.
Published: October 2005

The solution structure of protein AF2095 from the thermophilic archaea Archaeglobus fulgidis, a 123‐residue (13.6‐kDa) protein, has been determined by NMR methods. The structure of AF2095 is comprised of four α‐helices and a mixed β‐sheet consisting of four parallel and anti‐parallel β‐strands, where the α‐helices sandwich the β‐sheet. Sequence and structural comparison of AF2095 with proteins from Homo sapiens, Methanocaldococcus jannaschii, and Sulfolobus solfataricus reveals that AF2095 is a peptidyl‐tRNA hydrolase (Pth2). This structural comparison also identifies putative catalytic residues and a tRNA interaction region for AF2095. The structure of AF2095 is also similar to the structure of protein TA0108 from archaea Thermoplasma acidophilum, which is deposited in the Protein Data Bank but not functionally annotated. The NMR structure of AF2095 has been further leveraged to obtain good‐quality structural models for 55 other proteins. Although earlier studies have proposed that the Pth2 protein family is restricted to archeal and eukaryotic organisms, the similarity of the AF2095 structure to human Pth2, the conservation of key active‐site residues, and the good quality of the resulting homology models demonstrate a large family of homologous Pth2 proteins that are conserved in eukaryotic, archaeal, and bacterial organisms, providing novel insights in the evolution of the Pth and Pth2 enzyme families.
Crystal structure of the E230Q mutant of cAMP‐dependent protein kinase reveals an unexpected apoenzyme conformation and an extended N‐terminal A helix
Authors: Wu Jian , Yang Jie , Kannan Natarajan , Madhusudan  , Xuong Nguyen‐Huu , Ten Eyck Lynn F. , Taylor Susan S.
Published: October 2005

Glu230, one of the acidic residues that cluster around the active site of the catalytic subunit of cAMP‐dependent protein kinase, plays an important role in substrate recognition. Specifically, its side chain forms a direct salt‐bridge interaction with the substrate's P‐2 Arg. Previous studies showed that mutation of Glu230 to Gln (E230Q) caused significant decreases not only in substrate binding but also in the rate of phosphoryl transfer. To better understand the importance of Glu230 for structure and function, we solved the crystal structure of the E230Q mutant at 2.8 Å resolution. Surprisingly, the mutant preferred an open conformation with no bound ligands observed, even though the crystals were grown in the presence of MgATP and the inhibitor peptide, IP20. This is in contrast to the wild‐type protein that, under the same conditions, prefers the closed conformation of a ternary complex. The structure highlights the importance of the electrostatic surface not only for substrate binding and catalysis, but also for the mechanism for closing the active site cleft. This surface mutation clearly disrupts the recognition and binding of substrate peptide so that the enzyme prefers an open conformation that cannot trap ATP. This is consistent with the reinforcing concepts of conformational dynamics and the synergistic binding of ATP and substrate peptide. Another unusual feature of the structure is the observation of the entire N terminus (Gly1–Thr32) assumes an extended α‐helix conformation. Finally, based on temperature factors, this mutant structure is more stable than the wild‐type C‐subunit in the apo state.
International outsourcing and incomplete contracts
Authors: Spencer Barbara J.
Published: October 2005

Abstract.  International outsourcing to lower cost countries such as China and India can best be understood through the enrichment of trade models to include concepts from industrial organization and contract theory that explain the vertical organization of production. The combination of trade with the choice of organizational form represents an important new area for both theoretical and empirical research. This survey paper provides a perspective on this new literature so as to gain insights into the forces driving international outsourcing. The paper focuses on relationship‐specific investment, incomplete contracts, and also search and matching, as fundamental concepts that explain outsourcing decisions. JEL classification: F1, L14
Buying power and strategic interactions
Authors: Erutku Can
Published: October 2005

Abstract.  This paper shows that buying power at the retail level can lead to a rise in wholesale price. As a result, retailers without buying power may increase their retail price. Nevertheless, total surplus is non‐decreasing in the degree of buying power possessed by the ‘dominant’ retailer. JEL classification: L13
Partial outsourcing, monitoring cost, and market structure
Authors: Shy Oz , Stenbacka Rune
Published: October 2005

Abstract.  We investigate firms’ outsourcing decisions when production requires a large number of inputs. The novelty of our approach is that it provides a testable framework to characterize the equilibrium fraction of outsourced inputs. We demonstrate that intensified competition in a Cournot market for the final good typically enlarges the set of outsourced components relative to those produced in‐house. The proportions of outsourced inputs are found to be strategic substitutes independently of whether firms compete with respect to quantities or prices in the market for the final good. JEL classification: D20, L22
Imperfect price discrimination, market structure, and efficiency
Authors: Liu Qihong , Serfes Konstantinos
Published: October 2005

Abstract.  We introduce a flexible third‐degree price discrimination framework by modeling the information firms possess about consumers’ locations (preferences) on the Salop circle as a partition. Higher information quality is translated into a partition refinement. In the limit, we obtain the perfect price discrimination paradigm. We show that the free‐entry equilibrium number of firms exhibits a U‐shape as a function of the quality of information. This implies that imperfect price discrimination generates the most efficient free‐entry outcome. JEL classification: D43, L11, L43
Inequality and trade
Authors: Mitra Devashish , Trindade Vitor
Published: October 2005

Abstract.  We incorporate demand‐side considerations in trade in a systematic but straightforward way. We do so by focusing on the role of inequality in the determination of trade flows and patterns. With non‐homothetic preferences, when countries are similar in all respects but asset inequality, we find that trade is driven by specialization in consumption, not production. Besides, these assumptions allow us to generate some interesting international spillover effects of redistributive policies. Finally, we study a model of monopolistic competition and find a novel V‐shaped relationship between the ratio of inter‐industry to intra‐industry trade and a country's inequality. JEL classification: F11, F12
Skill distribution and income disparity in a North‐South trade model
Authors: Abdel‐Rahman Hesham M.
Published: October 2005

Abstract.  What are the impacts of free trade agreement on the welfare of different types of workers in a developed country? What is the impact of free trade on a developed country's income disparity? What is the effect of free trade on the skill distribution of a developed country? The objective of this paper is to address the above questions in a two‐sector general‐equilibrium North‐South trade model in which both countries produce one final good and one high‐tech intermediate input. The final good is produced with the use of a high‐tech intermediate input and unskilled workers. Horizontally differentiated skilled workers produce the high‐tech intermediate input. Each country is populated by a continuum of unskilled workers with differential potential ability. Workers in the North and South can acquire skills by investment in training or education. Thus, skill distribution in the North and South is determined endogenously in the model through a self‐selection process. I characterize two different types of equilibria: a closed‐economy equilibrium without trade and a free trade equilibrium. Then, I investigate the impact of free trade, in the presence of training costs, on the skill distribution within each country, income disparity, and social welfare. JEL classification: D63, F10, J31
Bigger establishments in thicker markets:  can we explain early productivity differentials between Canada and the United States?
Authors: Inwood Kris , Keay Ian
Published: October 2005

Abstract.  We use establishment‐level data describing manufacturers located in 128 border and near‐border counties in Michigan, New York, Ohio, Pennsylvania, and Ontario to calculate Canadian relative to U.S. total factor productivity ratios for 25 industries. The data have been compiled from the manuscripts for the 1870 U.S. and 1871 Canadian census of manufacturing. Our results illustrate that the average U.S. establishment was approximately 7% more efficient than its Canadian counterpart in 1870/71. When we control for establishment size and market density the U.S. productivity advantage shrinks to slightly less than 3%.
Firm survival and exit in response to trade liberalization
Authors: Baggs Jen
Published: October 2005

Abstract.  This paper considers the implications of changing trade barriers for the survival of Canadian manufacturing firms. The findings suggest that Canadian tariff reductions decreased the probability of survival for Canadian firms while declines in American tariffs increased that probability. Combining these effects, two‐thirds of Canadian manufacturing firms saw their probability of survival increase as a result of the tariff reductions mandated by the Canada‐US Free Trade Agreement. However, the vulnerability of a firm to failure as a result of trade liberalization was mitigated by the characteristics of that firm, particularly scale and leverage. JEL classification: F1, L1
Exporting and performance: evidence from Chilean plants
Authors: Alvarez Roberto , López Ricardo A.
Published: October 2005

Abstract.  Recent empirical evidence documents the superior characteristics of exporters relative to non‐exporters. Three explanations for this phenomenon have been proposed: self‐selection; learning‐by‐exporting; and conscious self‐selection. We test these three hypotheses using plant‐level data from Chile. We find that plants that enter international markets show superior initial performance compared with non‐exporters, consistent with self‐selection; we observe increases in productivity after plants begin to export, which is consistent with learning‐by‐exporting. We also find strong evidence supporting the idea that self‐selection is a conscious process by which plants increase productivity with the purpose of becoming exporters. JEL classification: F14; O54; D21
Trade in the Triad: how easy is the access to large markets?
Authors: Fontagné Lionel , Mayer Thierry , Zignago Soledad
Published: October 2005

Abstract.  In this paper, we measure market access between the United States, the EU, and Japan (the Triad), using the effect of national borders on trade patterns. We investigate overall and industry‐level trends of bilateral trade openness and provide explanations for those using proxies for bilateral observed protection (tariffs and NTBs), home bias of consumers, product differentiation, and levels of FDI. The explanations related to actual protection, home bias and substitutability of goods put together explain a large part of the border effect between blocs of the Triad, although they do not explain the whole of the border effect puzzle. JEL classification: F12, F15
Influence of female age, body size and environmental conditions on annual egg production of the bullhead
Authors: Abdoli A. , Pont D. , Sagnes P.
Published: October 2005

A population of bullhead Cottus gobio inhabiting a mountainous river network, was examined for the influence of maternal condition (total length, LT, and age class in years) and environmental factors (water temperature and fish density) on fecundity, egg size and net annual reproductive effort (ER, defined as the ratio of total egg production mass to body mass) within several stocks. Regardless of location within the drainage network, bullhead reproduction was synchronous, with only a single batch and fecundity ranging from 69 to 896 eggs per female. As with LT fecundity increased with age, although the difference between age classes 5 and 6 years was smaller than between other age classes. Egg diameter also increased with age from age classes 2 to 4 years, but then tended to decrease for age classes 5–6 years. Multiple stepwise regression was used to examine the effect of female LT, water temperature and fish densities on bullhead egg production for each of the four age classes (2, 3, 4 and 5–6 years) separately. When statistically significant, water temperature always had a positive effect and fish densities a negative effect, on fecundity and egg size. The LT always had a positive effect on fecundity for all the age classes. In contrast, LT had a positive effect on egg size and ER only for female reaching maturity (2 years), whereas intermediate aged females (3–4 years) were insensitive and the oldest fish showed a negative response.
Individual‐level analysis of pre‐ and post first‐feed growth and development in Atlantic salmon
Authors: Gilbey J. , McLay A. , Houlihan D. , Verspoor E.
Published: October 2005

Atlantic salmonSalmo salarwere followed from egg to smoltification using genetic analysis to identify individuals and to link observations from pre‐ and post first feeding. Egg size and hatch timing significantly influenced alevin size at first feed but neither egg size, hatch timing or alevin sizes were correlated to size, condition factor or smolt status post first feed. In a hatchery environment the potential advantage gained by early hatching, larger alevin does not persist after first feeding. Different physiological and genetic complexes appear to influence growth in these two distinct phases of the Atlantic salmon's life‐cycle.
The effect of temperature on growth and early maturation in a wild population of Atlantic salmon parr
Authors: Baum D. , Laughton R. , Armstrong J. D. , Metcalfe N. B.
Published: October 2005

Atlantic salmon Salmo salar parr exposed to heated water effluent were larger than parr living upstream of the discharge. There was no effect, however, of temperature on the incidence of male parr maturation, despite the link between growth and maturation found in other studies. Mature parr upstream of the effluent were smaller than mature parr downstream of it, suggesting a higher size threshold for maturation in those parr exposed to the heated water. The small distance between upstream and downstream sampling sites probably precluded genetic differences between the parr, thus implying an environmental influence on the threshold size above which male parr matured.
Seaward migrating subyearling chinook salmon avoid overhead cover
Authors: Kemp P. S. , Gessel M. H. , Williams J. G.
Published: October 2005

Approximately three‐quarters of migrating autumn (fall) chinook salmon Oncorhynchus tshawytscha smolts avoided a covered channel and selected an uncovered channel when presented with a choice in an experimental flume. Rejection of overhead cover occurred prior to, but was rare post‐channel entrance. Smolts may selectively reject riparian cover as an adaptive behavioural response to minimize predation risk and enhance rates of migration. The findings have implications for fish bypass design and riparian habitat and culvert restoration.
Gastric evacuation of mixed stomach contents in predatory gadoids: an expanded application of the square root model to estimate food rations
Authors: Andersen N. G. , Beyer J. E.
Published: October 2005

A mechanistic gastric evacuation model of mixed stomach contents was established. Its simple generic nature should prove useful for studying predator‐prey interactions in fish communities. Only prey lengths were required as additional input. Surface dependent digestive processes were considered to act on equal fractions of individual prey‐cylinder surfaces. Primary and interactive effects of size, energy density and resistance to digestion of individual prey in a stomach were described by the model. Model predictions of results from experiments on gastric evacuation of meals composed of different prey types demonstrated the capability of this model, as opposed to previously applied model principles, to predict evacuation of mixed stomach contents involving the three above‐mentioned prey characteristics. The study furthermore illustrated that estimates of food ration might be severely biased by using improperly formulated effects of prey characters on gastric evacuation, and demonstrated that the new model holds the potential to predict food ration and diet composition for wild populations of predatory fishes.
Pikeperch habitat use within a canal network in spring
Authors: Poulet N. , Lek S. , Argillier C.
Published: October 2005

Thirteen pikeperch Sander lucioperca were implanted with acoustic transmitters and 10 were successfully tracked twice a week from March to early July in a drainage canal connected to a brackish lagoon located in the Rhône delta. Pikeperch was found in the main canal and in narrow tributaries, but never in the lagoon. Pikeperch avoided shallow parts of the canal and selected areas with high riparian vegetation (mainly trees). No between sexes differences occurred in habitat selection. At the basin scale, while both sexes remained in the upstream part of the canal during the spawning period, after spawning, females migrated downstream and also into the tributaries. This migration may have been induced by the movement of prey while males remained guarding the nests.
Allogeneic haematopoietic cell transplantation for chronic myelogenous leukaemia in the era of imatinib: a retrospective multicentre study
Authors: Bornhäuser Martin , Kröger Nicolaus , Schwerdtfeger Rainer , Schafer‐Eckart Karin , Sayer Herbert G. , Scheid Christoph , Stelljes Mattias , Kienast Joachim , Mundhenk Peter , Fruehauf Stefan , Kiehl Michael G. , Wandt Hannes , Theuser Catrin , Ehninger Gerhard , Zander Axel R. ,   for the Cooperative German Transplant Study Group
Published: October 2005

Abstract:  Objective: To analyse the results of allogeneic haematopoietic cell transplantation (HCT) in patients with advanced stages of Philadelphia chromosome‐positive chronic myelogenous leukaemia (CML) who had previously been treated with imatinib mesylate (IM). Methods: We analysed the outcome of 61 patients with CML who had received allogeneic HCT from sibling (n = 18) or unrelated (n = 43) donors after having been treated with IM. Forty‐one patients had received IM because of accelerated or blast phase CML. Conditioning therapy contained standard doses of busulfan (n = 25) or total‐body irradiation (n = 20) in conjunction with cyclophosphamide in the majority of cases. Sixteen patients received dose‐reduced conditioning with fludarabine‐based regimens. Results: The incidence of grades II–IV and III–IV graft‐versus‐host disease was 66% and 38% respectively. The probability of overall survival (OS), disease‐free survival (DFS) and relapse at 18 months for the whole patient cohort were 37%, 33% and 24% respectively. The probability of non‐relapse mortality (NRM) at 100 d and 12 months was 30% and 46% respectively. Univariate analysis showed that fludarabine‐based conditioning therapy, age ≥40 yr and >12 months interval between diagnosis and transplantation were associated with a significantly lower OS and DFS and a higher NRM. Conclusion: These data suggest that although pretreatment with IM is not an independent negative prognostic factor, it cannot improve the dismal prognosis of CML patients at high risk for transplant‐related mortality.
Evaluation of PIT‐tagging in cyprinids
Authors: Skov C. , Brodersen J. , Brönmark C. , Hansson L.‐A. , Hertonsson P. , Nilsson P. A.
Published: October 2005

Laboratory and field experiments were used to investigate how different marking procedures, with 23 mm PIT (passive integrated transponders) – tags, affected mortality, body condition and tag expulsion in small roach Rutilus rutilus and rudd Scardinus erythrophthalmus (117 to 163 mm total length). In a laboratory experiment mortality was low (≤ 6%) and only occurred among fishes that had their incision closed with sutures. The latter also had a specific growth rate that tended to be lower than the fish tagged without sutures. The different marking procedures did not adversely affect the body condition of fishes either in the laboratory experiment (after 37 days) or in the field experiment (up to 369 days). No tag expulsions were observed among laboratory fishes PIT‐tagged without sutures. Marking without the use of sutures to close the incision, appears to be the most appropriate PIT tagging procedure for small cyprinids.
A non‐invasive method to assess the impact of electronic tag insertion on stress levels in fishes
Authors: Lower N. , Moore A. , Scott A. P. , Ellis T. , James J. D. , Russell I. C.
Published: October 2005

The present study investigated, for the first time, a non‐invasive technique for monitoring cortisol levels in fishes that had been implanted with electronic transmitters. This technique involved the measurement of cortisol released into the water by individual fish. Carp Cyprinus carpio and roach Rutilus rutilus that had been tagged with miniature dummy acoustic transmitters responded to the surgical implantation of the tags with an immediate (1 to 4 h) increase in cortisol concentrations in the water. These amounts of cortisol were higher than in ‘handled only’ and ‘handled and anaesthetized’ groups. Estimated cortisol release rates for both species correlated well with the direct measurements in the water. In both species, water cortisol concentration and cortisol release rates returned to pre‐stress levels within 12 h of tag‐insertion, and remained low for the remainder of the experiment. The calculation of cortisol release rates highlighted a difference of a factor of about four between peak release rates in carp and roach. There was no evident long‐term cortisol stress response to the presence of a tag in the body cavity in either species.
Morphological characteristics in relation to diet in five coexisting Thai fish species
Authors: Ward‐Campbell B. M. S. , Beamish F. W. H. , Kongchaiya C.
Published: October 2005

Morphological characteristics and intestinal content were analysed for five species of coexisting freshwater fishes in Thailand:Rasbora caudimaculata,Schistura desmotes,Dermogenys pusillus,Xenentodon cancilaandMonopterus albus(all found in riffle habitats in Thai streams).Rasbora caudimaculata,S. desmotesandD. pusillusfed predominantly on ephemeropterans, hymenopterans and dipterans,X. cancilafed predominantly on fishes, and larger aquatic invertebrates such as Odonata, andM. albusfed on detritus as well as invertebrate prey such as crustaceans and Odonata. Intestine length, mouth height, mouth width, eye position and mouth orientation varied among all five species. Canonical analysis of discriminance of mouth height, width and intestine length showed a clear dispersion of species, which was supported by intestine content. Evolutionary processes leading to the present differences in morphological characters resulted in each of the five species consuming a different portion of the available resource base, thereby facilitating coexistence.
Heart rate responses to predation risk inSalmo truttaare affected by the rearing environment
Authors: Sundström L. F. , Petersson E. , Johnsson J. I. , Dannewitz J. , Höjesjö J. , Järvi T.
Published: October 2005

Both wild‐ and hatchery‐reared brown troutSalmotrutta, 18 months of age and of the same genetic origin, responded with increased heart rates (tachycardia) to a simulated predator attack on 2 consecutive days. Brown trout reared in the hatchery showed a more rapidly induced tachycardia compared with wild‐reared fish at day 1, but not day 2. During an undisturbed period several hours after attacks, hatchery‐reared brown trout maintained higher heart rates compared to wild‐reared fish on both days. Behavioural responses to the attack were very low for all fish, although hatchery‐reared fish tended to be more active than wild fish after the attack day 2. The observed differences may have had a genetic background caused by different selection regimes in the hatchery‐ and wild‐rearing environments, or could have been due to different phenotypic responses in the two environments.
Ovary development in Greenland halibut Reinhardtius hippoglossoides in west Greenland waters
Authors: Simonsen C. S. , Gundersen A. C.
Published: October 2005

Maturity in adult female Greenland halibut Reinhardtius hippoglossoides was studied in three areas in west Greenland waters: the inshore area in Disko Bay and two offshore areas, Baffin Bay and Davis Strait. The aim was to monitor maturity changes in the inshore fjords of Disko Bay over an extended period from winter to autumn and compare these findings with specimens from Baffin Bay and the presumed spawning area in Davis Strait. A significant difference in maturity level was observed in and between the three areas. In Disko Bay maturity indices increased significantly in August and September both with respect to the gonado‐somatic index (IG) and the size in the leading oocyte cohort. In the period February to May no significant changes were observed. Mature ovaries were only observed among fish >80 cm total length and only among a fraction of these large fish. Offshore areas of Baffin Bay, even though poorly sampled, showed similar signs in the maturity indices as in Disko Bay. Relative to Disko Bay and Baffin Bay, female fish in Davis Strait had more progressed maturity indices. Furthermore, almost all fish in Davis Strait showed signs of progressed maturity contrary to Disko and Baffin Bay. A large proportion of the Greenland halibut in Disko and Baffin Bay apparently did not begin the maturation cycle until very late in their life history or were repeat spawners with a multi‐year maturation cycle. These observations could thus support the hypothesis that Greenland halibut have a prolonged adolescent phase. Atresia was highest in the early phases of maturation in Greenland halibut but relatively high levels of atresia were also observed in fish in more advanced maturity phase. The first was ascribed to fecundity regulation while the latter could be linked to the fish's fitness condition but it was not possible to show this with the available condition index.
Coupling non‐invasive physiological assessments with telemetry to understand inter‐individual variation in behaviour and survivorship of sockeye salmon: development and validation of a technique
Authors: Cooke S. J. , Crossin G. T. , Patterson D. A. , English K. K. , Hinch S. G. , Young J. L. , Alexander R. F. , Healey M. C. , Van Der Kraak G. , Farrell A. P.
Published: October 2005

Approximately 200 km from the mouth of the Fraser River, British Columbia, Canada, adult sockeye salmon Oncorhynchus nerka, were gastrically implanted with radio transmitters without anaesthetic. Subsets of the transmitter implanted fish were also biopsied which included drawing blood from the caudal peduncle (3 ml), removal of gill tissue (0·03 g) and quantification of energetic status using a microwave fat meter. Several experiments were used to test the hypothesis that the biopsy had a negligible effect on the subsequent survival and migratory behaviour of transmitter implanted fish. In the first experiment, no difference was found in the survival (both 100%) or tag retention (both 100%) between the two treatment groups (transmitter implanted with and without biopsy) when fish were held in pens for 24 h in the marine environment. Similarly, in other experiments where fish were released to the ocean to resume their migratory journey, no statistical differences were found in the travel times of fish in the two treatment groups, or in the proportion of fish that passed in‐river telemetry checkpoints. These results indicated that the handling and biopsy methods produced similar levels of mortality and tag retention as the telemetry treatment alone and that any changes in behaviour between the two treatment groups did not adversely affect migration time. Based upon the evidence provided from the biotelemetry of >300 adult sockeye salmon, it was felt that this general type of approach could be applicable to other fish species.
Marking the European eel with oxytetracycline, alizarin red and coded wire tags: an evaluation of methods
Authors: Simon J. , Dörner H.
Published: October 2005

After 1 week, the mortality of European eel Anguilla anguilla after marking glass eels with oxytetracycline (OTC) and alizarin red (ALC), and farm eels with coded wire tags (CWTs) was 0% within all treatments. The suitability of implanting CWTs in the nose region (tag loss 94% after 1 week) and in the dorsal musculature (tag loss 4% after 1 week) was also examined.
Ovarian regression and apoptosis in the South American teleost Leporinus taeniatus Lütken (Characiformes, Anostomidae) from the São Francisco Basin
Authors: Santos H. B. , Rizzo E. , Bazzoli N. , Sato Y. , Moro L.
Published: October 2005

Involution and resorption of both postovulatory and atretic follicles were analysed in piau‐jejo Leporinus taeniatus(Characiformes, Anostomidae) in order to evaluate the role of apoptosis during ovarian regression. Histological and ultrastructural analyses showed hallmarks of apoptosis in the granulosa: aggregation of compacted chromatin against the nuclear envelope, cell shrinkage, surface blebbing, loss of cell adhesion and cell fragmentation into apoptotic bodies. Protein synthesis activity preceded the onset of the cell death. The breakdown of the basement membrane led to the detachment of the granulosa cells into the follicular lumen. TUNEL‐positive reactions were detected in in situ DNA fragmentation of granulosa of both postovulatory and atretic follicles. Apoptosis increased in a time‐dependent manner contributing to reduction of the follicular areas. The apoptotic index (per cent of apoptotic cells) of the granulosa increased in postovulatory follicles soon after spawning, then these follicles degenerated and only remnants were observed at 7 days. In contrast, the granulosa cells reabsorbed the yolk during follicular atresia and the apoptotic index increased only in the late stage of regression. The results indicated apoptosis as the major mechanism to rapidly eliminate postovulatory follicles and being an essential process in the ovarian regression after spawning.
Intestinal fluid volumes and transit of dosage forms as assessed by magnetic resonance imaging
Authors: SCHILLER C. , FRÖHLICH C.‐P. , GIESSMANN T. , SIEGMUND W. , MÖNNIKES H. , HOSTEN N. , WEITSCHIES W.
Published: October 2005

Aim : The gastrointestinal transit of sequentially administered capsules was investigated in relation to the availability of fluid along the intestinal lumen by magnetic resonance imaging.

Methods : Water‐sensitive magnetic resonance imaging was performed on 12 healthy subjects during fasting and 1 h after a meal. Specifiable non‐disintegrating capsules were administered at 7, 4 and 1 h prior to imaging.

Results : While food intake reduced the mean fluid volumes in the small intestine (105 ± 72 mL vs. 54 ± 41 mL, P < 0.01) it had no significant effect on the mean fluid volumes in the colon (13 ± 12 mL vs. 18 ± 26 mL). The mean number of separated fluid pockets increased in both organs after meal (small intestine: 4 vs. 6, P < 0.05; large intestine: 4 vs. 6, P < 0.05). The distribution of capsules between the small and large intestine was strongly influenced by food (colon: 3 vs. 17 capsules, P < 0.01).

Conclusions : The results show that fluid is not homogeneously distributed along the gut, which likely contributes to the individual variability of drug absorption. Furthermore, transport of fluid and solids through the ileocaecal valve is obviously initiated by a meal‐induced gastro‐ileocaecal reflex.
Helicobacter pylori first‐line treatment and rescue options in patients allergic to penicillin
Authors: GISBERT J. P. , GISBERT J. L. , MARCOS S. , OLIVARES D. , PAJARES J. M.
Published: October 2005

Background : Helicobacter pylori eradication is a challenge in patients allergic to penicillin, especially those who have failed a first‐eradication trial.

Aim : To assess the efficacy and tolerability of H. pylori first‐line treatment and rescue options in patients allergic to penicillin.

Methods : Prospective single centre study including 40 consecutive treatments administered to patients allergic to penicillin. Therapy regimens: First‐line (12 patients) omeprazole, clarithromycin and metronidazole for 7 days; second‐line (17 patients) ranitidine bismuth citrate, tetracycline and metronidazole for 7 days; third‐line (nine patients) rifabutin, clarithromycin and omeprazole for 10 days; and fourth‐line (two patients) levofloxacin, clarithromycin and omeprazole for 10 days. Outcome variable: a negative 13C‐urea breath test 8 weeks after completion of treatment.

Results : Per‐protocol/intention‐to‐treat eradication rates were: first‐line (64/58%); second‐line (ranitidine bismuth citrate; 53/47%); third‐line (rifabutin; 17/11%) and fourth‐line regimen (levofloxacin; 100/100%). Compliance with treatment was generally good, except with the rifabutin‐based regimen, which presented adverse effects in 89% of the patients, including four cases of myelotoxicity.

Conclusions : H. pylori‐infected patients who are allergic to penicillin may be treated with a first‐line treatment combining a proton‐pump inhibitor, clarithromycin and metronidazole. Rescue options may include a regimen with ranitidine bismuth citrate, tetracycline and metronidazole. A levofloxacin‐based rescue regimen (with proton‐pump inhibitor and clarithromycin) may also represent an alternative, even when two or more consecutive eradication treatments have previously failed. However, rifabutin + clarithromycin + proton‐pump inhibitor regimen is ineffective and poorly tolerated.
Did intense adverse media publicity impact on prescribing of paroxetine and the notification of suspected adverse drug reactions? Analysis of routine databases, 2001–2004
Authors: Martin Richard M. , May Margaret , Gunnell David
Published: October 2005

Aim

To document the impact on clinical practice in England of media attention around possible adverse effects of paroxetine.

Design

Analysis of national selective serotonin reuptake inhibitor (SSRI) prescribing trends and yellow‐card adverse drug reaction reports, 2001–2004.

Results

From a steady state in 2001, paroxetine prescribing declined sharply from April 2002, coinciding with a USA regulatory action; the subsequent decline in paroxetine prescribing was 1.87% per month (95% confidence interval − 2.06, −1.68). Other SSRI prescribing increased by 1% per month until a major UK review of SSRIs in children in December 2003, after which prescribing plateaued. Media publicity was associated with short‐term peaks in yellow‐card reports related to paroxetine.

Conclusion

Falls in paroxetine and other SSRI prescribing in the UK coincided, respectively, with regulatory communications from the USA and the UK, but associations may have noncausal or other explanations. Reports of adverse reactions to paroxetine appeared to increase after adverse media publicity about the drug.
Drug safety and the media
Authors: Waller Patrick C. , Evans Stephen J. W. , Beard Keith
Published: October 2005

This article reviews the problems that may arise as a result of media coverage of drug safety issues. In order to promote more balanced coverage and avoid unnecessary scares, professionals working in the area of drug safety should rethink their strategies for dealing with the media.