bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polo‐like‐kinase 1 (PLK1) as a molecular target to overcome SYK‐mediated resistance of B‐lineage acute lymphoblastic leukaemia cells to oxidative stress
Authors: Uckun Fatih M. , Ozer Zahide , Qazi Sanjive , Tuel‐Ahlgren Lisa , Mao Chen 
Published: November 2009

SummarySYK tyrosine kinase has emerged as a master regulator of cellular resistance to oxidative stress (OS) by mediating the activation of the anti‐apoptotic nuclear factor κB and phosphatidylinositol‐3 kinase/AKT pathways after OS exposure. Here, we present unprecedented experimental evidence that polo‐like kinase 1 (PLK1) is the upstream regulator of SYK in B‐lineage acute lymphoblastic leukaemia (ALL) cells. Selective inhibition of PLK‐1 with the leflunomide metabolite analogue α‐cyano‐β‐hydroxy‐β‐methyl‐N‐[4‐(trifluoromethoxy) phenyl]‐propenamide/LFM‐A12 abolished the resistance of B‐lineage ALL cells to OS by preventing the activation of the anti‐apoptotic SYK signal transduction pathway. Notably, LFM‐A12 treatments at non‐cytotoxic concentrations resulted in marked augmentation of clonogenic death in resistant human B‐lineage ALL cell lines challenged with OS. Further, LFM‐A12 augmented OS‐induced apoptosis of chemotherapy‐resistant primary leukaemic cells from relapsed B‐lineage ALL patients in vitro and markedly potentiated the in vivo anti‐leukaemic activity of total body irradiation (TBI) against leukaemia‐initiating cells in severe combined immunodeficient mouse xenograft models of B‐lineage ALL. This study is the first to identify PLK1 as a regulator of SYK tyrosine kinase and a molecular target to overcome SYK‐mediated resistance of B‐lineage ALL cells to OS.
Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation
Authors: Kröger Nicolaus , Shimoni Avichai , Schilling Georgia , Schwerdtfeger Rainer , Bornhäuser Martin , Nagler Arnon , Zander Axel R. , Heinzelmann Marion , Brand Ronald , Gahrton Gösta , Morris Curly , Niederwieser Dietger , De Witte Theo 
Published: November 2009

SummaryFrom 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine regimen followed by allogeneic SCT from unrelated donors. All patients showed leucocyte and platelet engraftment after a median of 15 and 19 d, respectively. Grade II–IV acute graft‐versus‐host disease (GvHD) occurred in 25% of patients and 35% had chronic GvHD. Overall response rate at day 100 was 95% including 46% complete remission (CR). Cumulative incidence of non‐relapse mortality at 1 year was 25% [95% confidence interval (CI): 13–37%] and was significantly lower for human leucocyte antigen (HLA)‐matched compared to ‐mismatched SCT (10% vs. 53%, P = 0·001). The cumulative incidence of relapse at 3 years was 55% (95% CI: 40–70%). After a median follow up of 43 months, the estimated 5‐year progression‐free and overall survival rates were 20% and 26% respectively and were significantly better for matched in CR at day 100 (41% vs. 7%, P = 0·04 and 56% vs. 16%, P = 0·02). We conclude that optimal donor selection is mandatory for a low non‐relapse mortality and high relapse incidence, which remains a major concern, should be improved by including post‐transplant strategies to upgrade remission status.
Practical prebiotics, probiotics and synbiotics for allergists: how useful are they?
Authors: Johannsen H. , Prescott S. L. 
Published: November 2009

SummaryWith the advent of the hygiene hypothesis, probiotics have provided an avenue of hope in curbing the allergic epidemic. The initial enthusiasm has been tempered by recognition of the inherent complexities of this approach. This review examines the current clinical evidence and practical issues in using probiotics and related products, for the prevention and treatment of allergic disease. So far, probiotics have shown more promise, albeit limited, in the primary prevention of allergic disease rather than in the treatment of established disease. These effects have largely been limited to the prevention of early childhood conditions such as eczema, with no consistent effects on other allergic outcomes. There is emerging evidence that clinical effects may be strain specific, but again these findings have been inconsistent. While there have been several meta‐analyses to examine probiotics in both the prevention and the treatment of allergic disease, these have been hampered by significant heterogeneity between studies, including wide variations in the strains used, the methods and timing of administration and the age and assessment of allergic outcomes. In any case, these have also become outdated by a series of new studies published in the last year. Although it is not yet clear exactly how the growing number of new studies will modify the results of meta‐analyses, it is likely that these will add yet further heterogeneity that will continue to make interpretation of pooled data difficult. At this stage, the effects of prebiotics, synbiotics and postbiotics are even less clear. Thus, while there is little doubt that microbiota modulate immune development and can prevent the allergic phenotype, the optimal way of achieving this is far from clear. Given the current level of evidence, it is not appropriate to recommend prebiotics/probiotics/synbiotics or postbiotics as a part of standard therapy or for the prevention of any allergic conditions. Further studies are needed to address the growing speculation that supplementation with a single probiotic strain may be oversimplistic and that approaches that have a more global effect on colonization may be warranted.
Histamine, histamine receptors and their role in immune pathology
Authors: Jutel M. , Akdis M. , Akdis C. A. 
Published: November 2009

SummaryThe important roles of histamine in body physiology and various pathologic events have been well established, whereas new and exciting findings are still being uncovered. Histamine is not only the major mediator of the acute inflammatory and immediate hypersensitivity responses, but has also been demonstrated to affect chronic inflammation and regulate several essential events in the immune response. The diverse effects of histamine on immune regulation are due to the differential expression and regulation of four histamine receptors (HR) and their distinct intracellular signals. Differences in the affinities of these receptors are highly decisive on the biological effects of histamine and agents that target HRs. In particular, the discovery of reciprocal regulation of T cell activity by H1 and H2 receptor activation indicating histamine‐cytokine cross‐talk, as well as the characterization of the fourth histamine receptor (HR4) and its expression on numerous immune and inflammatory cells have prompted a re‐evaluation of the actions of histamine. This accounts for a new potential for HR antagonists and agonists in targeting various immunopathologic conditions.
nsLTP and profilin are allergens in mustard seeds: cloning, sequencing and recombinant production of Sin a 3 and Sin a 4
Authors: Sirvent S. , Palomares O. , Vereda A. , Villalba M. , Cuesta‐Herranz J. , Rodríguez R. 
Published: November 2009

SummaryBackground
Patients allergic to mustard are frequently sensitized to peach.Objective
To identify and analyse new yellow mustard allergens that could be involved in IgE cross‐reactivity.Methods
Sera from mustard‐allergic patients with symptoms to peach were studied. Mass spectrometry analyses provided sequences of IgE‐reactive proteins. cDNAs encoding Sin a 3 and Sin a 4 were amplified by polymerase chain reaction, cloned and sequenced. The recombinant allergens were obtained in Pichia pastoris and Escherichia coli, respectively, and used for ELISA, immunoblotting and inhibition experiments. Sequence alignment was used to identify common IgE epitopes.Results
Sin a 3‐ and Sin a 4‐specific cDNAs encode for mature proteins of 92 and 131 amino acids that belong to nsLTP and profilin protein families, respectively. Sin a 3 and Sin a 4 showed 54% and 80% identity with allergenic nsLTP from peach and profilin from melon, respectively. Both recombinant allergens were IgE‐reactive in ELISA and immunoblotting. Peach pulp and peel, and melon extracts nearly abolished the IgE binding to recombinant Sin a 3 or recombinant Sin a 4 in immunoblotting.Conclusion
Sin a 3 (nsLTP) and Sin a 4 (profilin) were identified as new mustard allergens and showed IgE cross‐reactivity with fruits such as peach or melon, respectively. The knowledge of these two allergens will contribute towards better understand with cross‐reactivity between mustard and other plant food allergens, and their availability will provide physicians with useful tools for molecular diagnosis.
Angiogenesis in asthma
Authors: Ribatti D. , Puxeddu I. , Crivellato E. , Nico B. , Vacca A. , Levi‐Schaffer F. 
Published: November 2009

SummaryAsthma is a chronic inflammatory disease of the airways characterized by infiltration and activation of inflammatory cells and by structural changes, including subepithelial fibrosis, smooth muscle cells hypertrophy/hyperplasia, epithelial cell metaplasia and angiogenesis. These structural changes are thought to correlate with asthma severity and to account for the development of progressive lung function deterioration. The mechanism underlying airway angiogenesis in asthma and its precise clinical relevance have not yet been completely elucidated. This review provides recent data showing the contribution of allergic inflammation in increased airway vascularity and potential therapeutical approaches in asthma treatment by acting on bronchial microvascular changes.
Impact of invasive apple snails in Hong Kong on wetland macrophytes, nutrients, phytoplankton and filamentous algae
Authors: FANG LING , WONG PAK KI , LIN LI , LAN CHONGYU , QIU JIAN‐WEN 
Published: November 2009

Summary1. Grazing by invasive species can affect many aspects of an aquatic system, but most studies have focused on the direct effects on plants. We conducted mesocosm and laboratory experiments to examine the impact of the invasive apple snail Pomacea canaliculata on macrophytes, filamentous algae, nutrients and phytoplankton.2. In a freshwater pond, we confined 500 g of Myriophyllum aquaticum or Eichhornia crassipes with 0, 2, 4 or 8 apple snails in 1 m × 1 m × 1 m enclosures for approximately 1 month. Apple snails grazed heavily on both species of macrophytes, with higher overall weight losses at higher snail densities. The damage patterns differed between the two macrophytes. In M. aquaticum, both leaves and stems suffered from substantial herbivory, whereas in E. crassipes, only the roots suffered significant weight reduction.3. In addition to grazing on macrophytes, apple snails appeared to have controlled the growth of filamentous algae, as these did not develop in the snail treatments. The ability of P. canaliculata to control filamentous algae was supported by a laboratory experiment where the consumption was as high as 0.25 g g−1 snail DW d−1. Because of a lack of native herbivorous snails in the pond, the growth of filamentous algae (mainly Spirogyra sp.) reached 80.3 g m−2, forming a spongy pond scum in the no‐apple snail control. Together with previous reports that apple snails could eat the juveniles and eggs of other freshwater snails, our results indicated that P. canaliculata could have out‐competed native herbivorous snails from the pond by predation on their juveniles or eggs. Alternatively, P. canaliculata might have out‐competed them by monopolisation of food resources.4. Nitrogen and phosphorous concentrations remained low throughout both experiments and were not correlated with apple snail density. The treatment effects on chlorophyll a (Chl a) and phytoplankton composition varied in the two experiments. In the M. aquaticum experiment, with increasing snail density, Chl a increased, and the phytoplankton community became dominated by Cryptophyceae. In the E. crassipes experiment, Chl a level was independent of snail density, but with increasing snail density, the phytoplankton community became co‐dominated by Cryptophyceae, Chlorophyceae and Bacillariophyceae.5. Given the multiple effects of P. canaliculata on wetland biodiversity and function, management strategies should be developed to prevent its further spread. In invaded wetlands, strategies should be developed to eradicate the apple snail and re‐introduce native snails which can control the development of filamentous algae.
Interactions between leaf lifespan and defoliation frequency in temperate and tropical pastures: a review
Authors: Lemaire G. , Da Silva S. C. , Agnusdei M. , Wade M. , Hodgson J. 
Published: November 2009

AbstractIn continuously stocked swards or pastures the frequency at which individual tillers and individual leaves are defoliated by ruminant livestock, relative to leaf lifespan of the grass species within the sward, determines the proportion of each leaf defoliated before senescence, and hence the efficiency of harvesting of herbage. In this paper, sets of data obtained in a range of climatic conditions and with a range of grass species are used in order to document this relationship. It is shown that the frequency of defoliation of individual tillers or individual leaves is closely linked to the average stocking density used within a period of time for maintaining a steady state sward or pasture height, herbage mass or leaf area index. Consequently, any decrease in herbage growth rate should lead to a decrease in the efficiency of harvesting of herbage and then to a more than proportional decrease in total herbage consumption by ruminant livestock. These effects will be more important for grass species having short leaf lifespan than for species with long lifespan. In rotational stocking, the link between herbage growth rate and frequency of defoliation of leaves can be broken by controlling the grazing interval, so any decrease in herbage growth would not be systematically associated with a decrease in efficiency of harvesting of herbage. Rotational stocking should be more efficient than continuous stocking in low herbage production conditions, while in high herbage production systems rotational and continuous stocking would have similar efficiency. The implications of these conclusions for the management of swards and pastures to meet different objectives are discussed briefly.
Influence of cutting regime and fertilizer application on the botanical composition, yield and nutritive value of herbage of wet grasslands in Central Europe
Authors: Čop J. , Vidrih M. , Hacin J. 
Published: November 2009

AbstractThe changes in dry matter (DM) yield, botanical composition and nutritive value of herbage to ruminants of two wet grasslands, Arrhenatherum elatius grassland (Experiment 1) and a Molinia caerulea fen meadow (Experiment 2), in which a range of cutting and fertilizer treatments were imposed in 1999, were assessed after 4–7 years of treatment imposition. Both experiments had a split‐plot design with four replicates. In Experiment 1 the three main‐plot cutting treatments were two cuts with a delayed first cut, three cuts and four cuts during the growing season of each year. In Experiment 2 the cutting treatments were two cuts with a traditional harvest time, two cuts with a delayed first cut and three cuts. The four sub‐plot fertilizer treatments were an unfertilized control, application of a phosphorus and potassium (PK) fertilizer, application of a nitrogen (N) and PK fertilizer to the first cut only (N1PK) and application of PK plus N applied to each of two, three or four cuts (NcPK). Application of fertilizer influenced yield and botanical composition of herbage more than the cutting treatments while the opposite occurred for nutritive value of the herbage. Application of fertilizer increased the proportion of tall grasses in Experiment 1 and forbs in Experiment 2. The proportion of Equisetum palustre, present only in Experiment 1, was reduced from 0·33 to less than 0·01 by increased cutting frequency together with the NPK fertilizer treatments. In Experiment 1 diversity of vascular plants was negatively affected only by the four‐cuts treatment while on both wet grasslands other cutting and fertilizer application treatments had no effect. Changes in DM yield of herbage caused by the cutting and fertilizer application treatments were similar for both vegetation types with DM yield increased significantly by fertilizer application but only slightly or not reduced by increasing the cutting frequency. Nutritive value of herbage was positively correlated with cutting frequency and was most influenced at the first cut.
Processing of transgenic crop residues in stream ecosystems
Authors: Swan Christopher M. , Jensen Peter D. , Dively Galen P. , Lamp William O. 
Published: November 2009

Summary 1. Research in agricultural ecosystems is uncovering how the management of crop fields leads to the delivery of transgenic crop residues to adjacent waterways. Aquatic consumers encountering this material may be reduced in abundance and/or limit their feeding activity, subsequently altering organic matter breakdown rate, which is a key ecosystem process in streams. 2. We investigated the effect of the transgenic nature of senesced corn (Zea mays L.), tissue on breakdown rates, invertebrate abundance and invertebrate community composition in nine streams draining agricultural fields over 2 years (2004–2006). We studied corn tissue modified to express protein toxins from the bacterium Bacillus thuringiensis (Bt) from four hybrid families, each with its single, stacked and non‐Bt near‐isoline. 3. In 2004, we identified two instances whereby Bt leaf litter degraded slower (67–68%) than corresponding near isolines. At one site this was associated with significantly fewer individuals of Pycnopsyche sp., a leaf‐chewing caddisfly. In 2005–2006, no differences in breakdown were found between Bt and non‐Bt near isolines. Multivariate analysis of invertebrate communities found no difference associated with Bt treatment. 4. Principle components analysis identified important abiotic factors as explanatory variables influencing breakdown, but no interaction was found between these and Bt treatment. Breakdown was strongly related to total invertebrate abundance occurring on experimental litter bags, but this did not interact with Bt treatment across all hybrid × isoline × site combinations. 5. Synthesis and applications. Ecological interactions facilitate breakdown of allochthonous detritus, and understanding the potential disruption of these interactions is important to the management of ecosystem processes. The results from our study suggests that corn tissue breakdown is unlikely to be altered by Bt, but more so by hybrid‐ and site‐specific factors such as nutrients. Management of agricultural streams will need to consider multiple sources of stress at larger scales, such as nutrient loading and temperature, which probably overwhelm the potential for consumer mediation of ecosystem processes in these ecosystems.
Diversity enhances community recovery, but not resistance, after drought
Authors: Van Ruijven Jasper , Berendse Frank 
Published: November 2009

Summary1. There is growing concern that the current loss of biodiversity may negatively affect ecosystem functioning and stability. Although it has been shown that species loss may reduce biomass production and increase temporal variability, experimental evidence that species loss affects ecosystem resistance and resilience after perturbation is limited.2. Here, we use the response of experimental plant communities – which differ in diversity – to a natural drought to disentangle the effects of diversity and biomass on resistance, recovery and resilience.3. Resistance to drought decreased with diversity, but this pattern was highly dependent upon pre‐drought biomass. When corrected for biomass, no relationship between diversity and resistance was observed: at each level of diversity, biomass production was reduced by approximately 30%.4. In contrast, recovery (change in biomass production after drought) increased with diversity and was independent of biomass. Resilience (measured as the ratio of post‐ to pre‐drought biomass) was similar at each level of diversity.5. Synthesis. On the one hand, our results confirm earlier findings that a positive relationship between diversity and resistance is mainly driven by pre‐perturbation performance rather than by diversity. However, the results also show that recovery after drought strongly increased with diversity, independent of performance. We conclude that it is this diversity‐dependent recovery which allowed diverse, productive communities to reach the same level of resilience as less diverse (and productive) communities. This finding provides strong experimental evidence for the insurance hypothesis.
Nuclear and mitochondrial DNA reveal contrasting evolutionary processes in populations of deer mice (Peromyscus maniculatus)
Authors: YANG DOU‐SHUAN , KENAGY G. J. 
Published: November 2009

AbstractWe investigated a major geographic break in mitochondrial DNA (mtDNA) haplotypes in deer mice, Peromyscus maniculatus, by analysing spatial variation in a 491‐bp fragment of the mtDNA control region from 455 samples distributed across a north–south transect of 2000 km in Western North America. To determine whether the mtDNA break was reflected in the nuclear genome, we then compared spatial variation in 13 nuclear microsatellites of 95 individuals surrounding the mtDNA break. Using a canonical correlation analysis we found that nuclear genomic variation was not correlated with mtDNA differentiation. The contrasting patterns of variation in mtDNA and nuclear DNA are consistent with a hypothesis of historic genetic drift that occurred in isolated refugia combined with recent gene flow between the formerly isolated refugial populations. A Mantel test of genetic vs. geographic distance revealed that recent gene flow between deer mouse populations has been high. We conclude that past vicariant events associated with Pleistocene climate changes together with recent gene flow have created the observed intra‐specific cytonuclear discordance in Western North America.
New thermochronometric constraints on the rapid Palaeogene exhumation of the Cordillera Darwin complex and related thrust sheets in the Fuegian Andes
Authors: Gombosi David J. , Barbeau Jr David L. , Garver John I. 
Published: November 2009

AbstractThermal modelling of new fission‐track and (U–Th–Sm)/He data from the Fuegian Andes reveals rapid cooling (∼12–48 °C Ma−1) during the middle and late Eocene followed by slow cooling (∼1.5 °C Ma−1) to the Recent. We interpret the rapid cooling as a result of exhumation from contractional uplift within the crystalline interior of the orogen. This interpretation is consistent with independent evidence of Eocene shortening, flexural subsidence and provenance changes in the study area, and is approximately coeval with marine geochemical evidence of the onset of Drake Passage opening. In light of the Palaeogene history of Nazca‐South American plate convergence and the differences in shortening magnitudes and exhumation histories between the Fuegian and Patagonian Andes, our data support Eocene development of the Patagonian orocline, which also provides a plausible explanation for early opening of Drake Passage.