bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addiction research centres and the nurturing of creativity: Centre for Social Research on Alcohol and Drugs (SoRAD), Stockholm University, Sweden
Authors: Stenius Kerstin , Ramstedt Mats , Olsson Börje 
Published: February 2010

ABSTRACTThe Centre for Social Research on Alcohol and Drugs (SoRAD) was established as a national research centre and department within the Faculty of Social Science at Stockholm University in 1997, following a Government Report and with the aim to strengthen social alcohol and drug research. Initially, core funding came from the Swedish Council for Working Life and Social Research and from the Ministry of Health and Social Affairs for several long‐term projects. Today, SoRAD, with 25 senior and junior researchers, has core funding from the university but most of its funding comes from external national and international grants. Research is organized under three themes: consumption, problems and norms, alcohol and drug policy and societal reactions, treatment and recovery processes. SoRADs scientific approach, multi‐disciplinarity, a mix of qualitative and quantitative methods and international comparisons was established by the centre's first leader, Robin Room. Regular internal seminars are held and young researchers are encouraged to attend scientific meetings and take part in collaborative projects. SoRAD researchers produce government‐funded monthly statistics on alcohol consumption and purchase, and take part in various national government committees, but SoRADs research has no clear political or bureaucratic constraints. One of the future challenges for SoRAD will be the proposed system for university grants allocation, where applied social science will have difficulties competing with basic biomedical research if decisions are based on publication and citation measures.
Predictors of the recurrence of hepatic encephalopathy in lactulose‐treated patients
Authors: BAJAJ J. S. , SANYAL A. J. , BELL D. , GILLES H. , HEUMAN D. M. 
Published: February 2010

Aliment Pharmacol Ther 31, 1012–1017SummaryBackground  Lactulose is considered first‐line therapy for hepatic encephalopathy. However, the effect of adherence with lactulose on recurrence of hepatic encephalopathy outside clinical trials remains unclear.Aim  To determine the association of lactulose use with recurrence of hepatic encephalopathy episodes.Methods  Patients with cirrhosis who were initiated on lactulose after an index hepatic encephalopathy episode in a liver‐transplant centre were retrospectively reviewed. Recurrence of hepatic encephalopathy, precipitating factors and adherence on lactulose were investigated using chart review and electronic pharmacy records. Patients with/without hepatic encephalopathy recurrence were compared, and predictors of recurrence were analysed.Results  A total of 137 patients with cirrhosis (age 55 ± 6years, MELD 17 ± 7) who were initiated on lactulose after the index hepatic encephalopathy episode were included. Of these, 103 patients developed recurrent hepatic encephalopathy 9 ± 1 months after their index episode; 39 (38%) of these were not adherent on lactulose, 56 (54%) were adherent and 8 (8%) had lactulose‐associated dehydration leading to recurrence. Recurrent hepatic encephalopathy precipitants in lactulose‐adherent patients were sepsis (19%), GI bleeding (15%), hyponatremia (4%) and TIPS (7%). Overall, all patients who did not suffer recurrence were adherent on lactulose. In contrast, the adherence rate for those who recurred was only 64% (P = 0.00001). On multivariate regression, lactulose non‐adherence (OR 3.26) and MELD score (OR 1.14) were the factors that predicted recurrence.Conclusion  Lactulose non‐adherence and lactulose‐associated dehydration were associated with nearly half of recurrent hepatic encephalopathy episodes.
Haematopoeitic cell transplantation for Fanconi anaemia – when and how?
Authors: MacMillan Margaret L. , Wagner John E. 
Published: February 2010

SummaryAllogeneic haematopoietic cell transplantation (HCT) remains the only treatment that can correct the haematological manifestations in patients with Fanconi anaemia. Over the last two decades, sequential changes to the approach to HCT have resulted in reduced regimen‐related toxicity, superior engraftment and less graft‐versus‐host disease (GVHD), resulting in improved survival. The two pivotal changes that most influenced these improvements were the addition of fludarabine to the preparative regimen to augment engraftment, and the use of T cell depletion to reduce GVHD. With these improved HCT outcomes, indications for HCT are quite consistent regardless of donor source. Emphasis is now being placed on developing HCT regimens that will improve quality of life by reducing late effects, particularly the risk of malignancy, sterility and endocrinopathies. This paper will review the unique challenges of HCT in FA patients, with particular emphasis on the timing and approach to HCT.
Prolonged survival with improved tolerability in higher‐risk myelodysplastic syndromes: azacitidine compared with low dose ara‐C
Authors: Fenaux Pierre , Gattermann Norbert , Seymour John F. , Hellström‐Lindberg Eva , Mufti Ghulam J. , Duehrsen Ulrich , Gore Steven D. , Ramos Fernando , Beyne‐Rauzy Odile , List Alan , McKenzie David , Backstrom Jay , Beach Charles L. 
Published: February 2010

SummaryIn the phase III AZA‐001 trial, low‐dose cytarabine (LDara‐C), the most widely used low‐dose chemotherapy in patients with higher‐risk myelodysplastic syndrome (MDS) who are ineligible for intensive treatment, was found to be associated with poorer survival compared with azacitidine. This analysis further compared the efficacy and the toxicity of these two drug regimens. Before randomization, investigators preselected patients to receive a conventional care regimen, one of which was LDara‐C. Of 94 patients preselected to LDara‐C, 45 were randomized to azacitidine and 49 to LDara‐C. Azacitidine patients had significantly more and longer haematologicalal responses and increased red blood cell transfusion independence. Azacitidine prolonged overall survival versus LDara‐C in patients with poor cytogenetic risk, presence of −7/del(7q), and French‐American‐British subtypes refractory anaemia with excess blasts (RAEB) and RAEB in transformation. When analyzed per patient year of drug exposure, azacitidine treatment was associated with fewer grade 3–4 cytopenias and shorter hospitalisation time than LDara‐C in these higher‐risk MDS patients.
Patterns in taxonomic and functional diversity of lake phytoplankton
Authors: LONGHI MARIA L. , BEISNER BEATRIX E. 
Published: February 2010

Summary1. Patterns in phytoplankton diversity in lakes and their relationships with environmental gradients have been traditionally based on taxonomic analyses and indices, even though measures of functional diversity (FD) might be expected to be more responsive to such gradients.2. We assessed the influence of water column physical structure, and other components of the overall environment, on lake phytoplankton diversity using two taxonomically based indices [species richness (S) and the Shannon index (H’)] and a FD index, to determine whether these different measures respond in similar ways to habitat structure. The study encompassed 45 lakes in Eastern Canada, within two lake districts [the Eastern Townships Region (ETR) and Laurentians Region (LR)] that vary in geology and landscape and in lake morphometry and chemistry.3. Across all lakes, S and H’ were higher in lakes having greater vertical temperature heterogeneity and higher susceptibility to wind mixing. In addition, H’ declined with total phosphorus concentration. FD was only related to maximum lake depth, a variable that integrates many other habitat features.4. Further insight into the factors affecting phytoplankton diversity was obtained by contrasting the two regions. The taxonomically based diversity measures differed little between the regions, while FD was higher in the ETR where more trait variants were present and more evenly distributed amongst species. Whereas factors driving S did not differ between the regions, we found region‐dependent patterns in the relationships of H’ and FD with maximum lake depth: both indices decreased with maximum depth in the region with lakes more exposed to wind (ETR) but increased in the more hilly landscape where lakes are more sheltered from wind mixing (LR).5. Our study demonstrates that, for phytoplankton communities, a FD index can show simpler and stronger responses to environmental drivers than a taxonomically based index, while shedding further light onto the functional traits that are important in particular lake categories.
Long‐term variation in the littoral food web of an acidified mountain lake
Authors: LAYER KATRIN , HILDREW ALAN , MONTEITH DON , WOODWARD GUY 
Published: February 2010

AbstractEvidence of chemical recovery from acidification in European freshwaters has emerged in recent years, with many previously damaged systems responding to decades of reduced acidifying emissions. Biological recovery, however, has often lagged behind, and this has been ascribed to several possible mechanisms, including inertia in the food web. We examined two decades of change in hindcasted food webs for Lochnagar, a Scottish mountain lake, to make inferences about the potential dynamical stability of the system and to assess the prospects for future biological recovery. Although community composition tracked temporal changes in acidity, this was neither sustained nor directional, and mainly manifested as shifts in relative abundances rather than the establishment of more acid‐sensitive species. The food web was highly interconnected and reticulate, especially in years when species richness was low, and subsidized by external inputs of detritus. Among the primary consumers, generalist herbivore–detritivores maintained feeding links with the scant algal resources, which appeared insufficient to support viable populations of specialist grazers. Together, these characteristics, which are shared with many other acidified freshwaters, are likely to make the community dynamically stable and resistant to invasions of potential new colonists, thereby slowing the pace of future biological recovery.
Land‐use and climate change effects on population size and extinction risk of Andean plants
Authors: FEELEY KENNETH J. , SILMAN MILES R. 
Published: February 2010

AbstractAndean plant species are predicted to shift their distributions, or ‘migrate,’ upslope in response to future warming. The impacts of these shifts on species' population sizes and their abilities to persist in the face of climate change will depend on many factors including the distribution of individuals within species' ranges, the ability of species to migrate and remain at equilibrium with climate, and patterns of human land‐use. Human land‐use may be especially important in the Andes where anthropogenic activities above tree line may create a hard barrier to upward migrations, imperiling high‐elevation Andean biodiversity. In order to better understand how climate change may impact the Andean biodiversity hotspot, we predict the distributional responses of hundreds of plant species to changes in temperature incorporating population density distributions, migration rates, and patterns of human land‐use. We show that plant species from high Andean forests may increase their population sizes if able to migrate onto the expansive land areas above current tree line. However, if the pace of climate change exceeds species' abilities to migrate, all species will experience large population losses and consequently may face high risk of extinction. Using intermediate migration rates consistent with those observed for the region, most species are still predicted to experience population declines. Under a business‐as‐usual land‐use scenario, we find that all species will experience large population losses regardless of migration rate. The effect of human land‐use is most pronounced for high‐elevation species that switch from predicted increases in population sizes to predicted decreases. The overriding influence of land‐use on the predicted responses of Andean species to climate change can be viewed as encouraging since there is still time to initiate conservation programs that limit disturbances and/or facilitate the upward migration and persistence of Andean plant species.
Faunal evidence for a late quaternary trans‐Antarctic seaway
Authors: BARNES DAVID K. A. , HILLENBRAND CLAUS‐DIETER 
Published: February 2010

AbstractCollapse of the West Antarctic Ice Sheet (WAIS) would raise global sea level by ∼3.3–5 m. Ice‐sheet models and geological data suggest at least one collapse has happened during the last 1.1 Ma, and some scenarios of future climate change predict a collapse within the next two centuries. A complete WAIS collapse would open shallow seaways across West Antarctica, potentially enabling exchange of animals between West Antarctic seas. We investigated biological evidence for past connectivity between different regions of Antarctica by comparing the composition of modern bryozoan assemblages from the continental margin around Antarctica. Surprisingly, we found most similarity between two areas which are not currently connected – the shelves of the Weddell Sea (WS) and Ross Sea (RS). We evaluated three hypotheses to explain this and conclude that bryozoans most likely dispersed through a trans‐Antarctic seaway that opened in response to a WAIS collapse and connected the WS and RS shelves. These bryozoans must have survived glaciations(s) during subsequent ice ages in refuges, whereas they were wiped out in most other regions of the Antarctic shelf. After the last glacial period, bryozoan assemblages could freely disperse between many of the regions we examined (e.g. Antarctic Peninsula and South Shetland Islands), which has allowed recolonization of areas in which bryozoans had been eradicated during the last ice age. For the bryozoans on the WS and RS shelves to be more similar than those which are in close proximity means the trans‐Antarctic seaway may have been as late as the last few interglacials. Current rates of warming are exceptional compared with the near past glacial cycles so our study, the strongest faunal evidence of WAIS collapse during the recent geological past, thus supports predictions of a near future WAIS collapse (with considerable global sea level implications) and resultant future major faunal exchanges.
Enhancement of effector CD8+ T‐cell function by tumour‐associated B7‐H3 and modulation of its counter‐receptor triggering receptor expressed on myeloid cell‐like transcript 2 at tumour sites
Authors: Kobori Hiroko , Hashiguchi Masaaki , Piao Jinhua , Kato Moriyuki , Ritprajak Patcharee , Azuma Miyuki 
Published: February 2010

SummaryB7‐H3 is a B7‐family co‐stimulatory molecule and is broadly expressed on various tissues and immune cells. Transduction of B7‐H3 into some tumours enhances anti‐tumour responses. We have recently found that a triggering receptor expressed on myeloid cell‐like transcript 2 (TLT‐2) is a receptor for B7‐H3. Here, we examined the roles of tumour‐associated B7‐H3 and the involvement of TLT‐2 in anti‐tumour immunity. Ovalbumin (OVA)257–264‐specific OT‐I CD8+ T cells exhibited higher cytotoxicity against B7‐H3‐transduced OVA‐expressing tumour cells (B7‐H3/E.G7) in vitro and selectively eliminated B7‐H3/E.G7 cells in vivo. The presence of B7‐H3 on target cells efficiently augmented CD8+ T‐cell‐mediated cytotoxicity against alloantigen or OVA, whereas the presence of B7‐H3 in the priming phase did not affect the induced cytotoxicity. B7‐H3 transduction into five tumour cell lines efficiently reduced their tumorigenicity and regressed growth. Treatment with either anti‐B7‐H3 or anti‐TLT‐2 monoclonal antibody accelerated growth of a tumour that expressed endogenous B7‐H3, suggesting a co‐stimulatory role of the B7‐H3–TLT‐2 pathway. The TLT‐2 was preferentially expressed on CD8+ T cells in regional lymph nodes, but was down‐regulated in tumour‐infiltrating CD8+ T cells. Transduction of TLT‐2 into OT‐I CD8+ T cells enhanced antigen‐specific cytotoxicity against both parental and B7‐H3‐transduced tumour cells. Our results suggest that tumour‐associated B7‐H3 directly augments CD8+ T‐cell effector function, possibly by ligation of TLT‐2 on tumour‐infiltrating CD8+ T cells at the local tumour site.
Lipopolysaccharide induces calcitonin gene‐related peptide in the RAW264.7 macrophage cell line
Authors: Ma Weiya , Dumont Yvan , Vercauteren Freya , Quirion Remi 
Published: February 2010

SummaryCalcitonin gene‐related peptide (CGRP) is widely distributed and plays important roles in a wide array of biological functions. It is enriched in primary sensory neurons and hence involved in nociception and neurogenic inflammation. Recent studies have shown that CGRP can be produced by immune cells such as monocytes/macrophages following inflammatory stimulation, suggesting a role in innate immunity. However, it is unclear how CGRP is up‐regulated in macrophages and if it plays a role in macrophage functions such as the production of cytokines and chemokines. Using enzyme‐linked immunosorbent assay (ELISA) and multiplex ELISA, lipopolysaccharide (LPS) was found to induce CGRP in the RAW 264.7 macrophage cell line. LPS‐induced inflammatory mediators such as nerve growth factor (NGF), interleukin‐1β (IL‐1β), IL‐6, prostaglandin E2(PGE2) and nuclear factor‐κB (NF‐κB) signalling are involved in inducing CGRP, whereas the NGF receptor trkA and CGRP receptor signalling pathways are unexpectedly involved in suppressing LPS‐induced CGRP, which leads to the fine‐tune regulation of CGRP release. Exogenous CGRP and CGRP receptor antagonists, in a concentration‐dependent manner, stimulated, inhibited or had no effect on basal or LPS‐induced release of monocyte chemoattractant protein‐1, IL‐1β, IL‐6, tumour necrosis factor‐α and IL‐10 in RAW macrophages. The ligand‐concentration‐dependent regulation of the production of inflammatory mediators by CGRP receptor signalling is a novel mechanism underlying the stimulating and suppressing role of CGRP in immune and inflammatory responses. Together, our data suggest that monocytes/macrophages are an important source of CGRP. Inflammation‐induced CGRP has a positive or negative reciprocal effect on the production of other pro‐ and anti‐inflammatory mediators. Thereby CGRP plays both facilitating and suppressing roles in immune and inflammatory responses.
Changes in chromatin structure and methylation of the human interleukin‐1β gene during monopoiesis
Authors: Wessels Inga , Fleischer Daniela , Rink Lothar , Uciechowski Peter 
Published: February 2010

SummaryInterleukin‐1β (IL‐1β) induces the expression of a variety of proteins responsible for acute inflammation and chronic inflammatory diseases. However, the molecular regulation of IL‐1β expression in myeloid differentiation has not been elucidated. In this study the chromatin structure of the IL‐1β promoter and the impact of methylation on IL‐1β expression in monocytic development were examined. The results revealed that the IL‐1β promoter was inaccessible in undifferentiated promyeloid HL‐60 cells but highly accessible in differentiated monocytic cells which additionally acquired the ability to produce IL‐1β. Accessibilities of differentiated cells were comparable to those of primary monocytes. Lipopolysaccharide (LPS) stimulation did not affect promoter accessibility in promyeloid and monocytic HL‐60 cells, demonstrating that the chromatin remodelling of the IL‐1β promoter depends on differentiation and not on the transcriptional status of the cell. Demethylation via 5‐aza‐2′‐deoxycytodine led to the induction of IL‐1β expression in undifferentiated and differentiated cells, which could be increased after LPS stimulation. Our data indicate that the IL‐1β promoter is reorganized into an open poised conformation during monopoiesis being a privilege of mature monocytes but not of the entire myeloid lineage. As a second mechanism, IL‐1β expression is regulated by methylation acting independently of the developmental stage of myeloid cells.
New insights into the blood‐stage transcriptome of Plasmodium falciparum using RNA‐Seq
Authors: Otto Thomas D. , Wilinski Daniel , Assefa Sammy , Keane Thomas M. , Sarry Louis R. , Böhme Ulrike , Lemieux Jacob , Barrell Bart , Pain Arnab , Berriman Matthew , Newbold Chris , Llinás Manuel 
Published: February 2010

SummaryRecent advances in high‐throughput sequencing present a new opportunity to deeply probe an organism's transcriptome. In this study, we used Illumina‐based massively parallel sequencing to gain new insight into the transcriptome (RNA‐Seq) of the human malaria parasite, Plasmodium falciparum. Using data collected at seven time points during the intraerythrocytic developmental cycle, we (i) detect novel gene transcripts; (ii) correct hundreds of gene models; (iii) propose alternative splicing events; and (iv) predict 5′ and 3′ untranslated regions. Approximately 70% of the unique sequencing reads map to previously annotated protein‐coding genes. The RNA‐Seq results greatly improve existing annotation of the P. falciparum genome with over 10% of gene models modified. Our data confirm 75% of predicted splice sites and identify 202 new splice sites, including 84 previously uncharacterized alternative splicing events. We also discovered 107 novel transcripts and expression of 38 pseudogenes, with many demonstrating differential expression across the developmental time series. Our RNA‐Seq results correlate well with DNA microarray analysis performed in parallel on the same samples, and provide improved resolution over the microarray‐based method. These data reveal new features of the P. falciparum transcriptional landscape and significantly advance our understanding of the parasite's red blood cell‐stage transcriptome.
Genetic Variance in Cadmium Tolerance and Accumulation in Wheat Materials Differing in Ploidy and Genome at Seedling Stage
Authors: Ci D. , Jiang D. , Wollenweber B. , Dai T. , Jing Q. , Cao W. 
Published: February 2010

AbstractCadmium (Cd) tolerance and accumulation in wheat varieties differing in ploidy and genome were investigated at seedling stage under controlled environmental conditions. The wheat varieties included six diploid, eight tetraploid, seven hexaploid and three octoploid species together with wheat relatives containing different genomes. Parameters of growth and photosynthesis were measured and the ratio of a given parameter under Cd treatment to that of the control was referred to as the Cd‐tolerant index of this parameter. Cd concentrations in shoots and roots, Cd accumulation in shoots (SCA) and Cd translocation (ratio of SCA to total Cd accumulation in plants) of the wheat varieties differing in ploidies generally decreased from octoploid to diploid, except for material containing the CCUU genome. It was found that Cd tolerance of these 24 wheat varieties varied with different ploidy and genomes at seedling stage. B and D genomes played a positive role, whereas the R genome played a negative role in Cd tolerance. By contrast, there were no significant differences between ploidies in Cd tolerance based on the observed growth and photosynthesis parameters. Using principal components analysis and cluster analysis, Triticum boeoticum Boiss was found to be the most Cd‐tolerant variety exhibiting low Cd translocation rates, whereas T. aestivum cv. Huixianhong and Jinghui 1 were identified as the most Cd‐sensitive varieties showing also higher Cd translocation rates.