bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspase-1 Mediates Resistance in Murine Melioidosis
Authors: Breitbach Katrin , Sun Guang Wen , Köhler Jens , Eske Kristin , Wongprompitak Patimaporn , Tan Gladys , Liu Yichun , Gan Yunn-Hwen , Steinmetz Ivo 
Published: January 2009

ABSTRACT

The gram-negative rod
Burkholderia pseudomallei
is the causative agent of melioidosis, a potentially fatal disease which is endemic in tropical and subtropical areas. The bacterium multiplies intracellularly within the cytosol, induces the formation of actin tails, and can spread directly from cell to cell. Recently, it has been shown that
B. pseudomallei
can induce caspase-1-dependent cell death in macrophages. The aim of the present study was to further elucidate the role of caspase-1 during
B. pseudomallei
infection. In vivo experiments with
caspase-1
−/−
mice revealed a high susceptibility to
B. pseudomallei
challenge. This phenotype was associated with a significantly higher bacterial burden 2 days after infection and decreased gamma interferon (IFN-γ) and interleukin-18 cytokine levels 24 h after infection compared to control animals.
caspase-1
−/−
bone marrow-derived macrophages (BMM) exhibited strong caspase-3 expression and reduced cell damage compared to wild-type (WT) cells during early
B. pseudomallei
infection, indicating “classical” apoptosis, whereas WT BMM showed signs of rapid caspase-1-dependent cell death. Moreover, we found that
caspase-1
−/−
BMM had a strongly increased bacterial burden compared to WT cells 3 h after infection under conditions where no difference in cell death could be observed between both cell populations at this time point. We therefore suggest that caspase-1-dependent rapid cell death might contribute to resistance by reducing the intracellular niche for
B. pseudomallei
, but, in addition, caspase-1 might also have a role in controlling intracellular replication of
B. pseudomallei
in macrophages. Moreover, caspase-1-dependent IFN-γ production is likely to contribute to resistance in murine melioidosis.
Trypanosoma cruziPromotes Neuronal and Glial Cell Survival through the Neurotrophic Receptor TrkC
Authors: Weinkauf Craig , PereiraPerrin Mercio 
Published: January 2009

ABSTRACTTrypanosoma cruzi, the agent of Chagas' disease, promotes neuron survival through receptor tyrosine kinase TrkA and glycosylphosphatidylinositol-anchored glial cell-derived family ligand receptors (GFRα). However, these receptors are expressed by only a subset of neurons and at low levels or not at all in glial cells. Thus,T. cruzimight exploit an additional neurotrophic receptor(s) to maximize host-parasite equilibrium in the nervous system. We show here thatT. cruzibinds TrkC, a neurotrophic receptor expressed by glial cells and many types of neurons, and that the binding is specifically inhibited by neurotrophin-3, the natural TrkC ligand. Coimmunoprecipitation and competition assays show that thetrans-sialidase/parasite-derived neurotrophic factor (PDNF), previously identified as a TrkA ligand, mediates theT. cruzi-TrkC interaction. PDNF promotes TrkC-dependent mitogen-activated protein kinase signaling, neurite outgrowth, and survival of genetically engineered PC12 neuronal cells and glial Schwann cells in a TrkC-dependent manner. Thus, TrkC is a new neurotrophic receptor thatT. cruziengages to promote the survival of neuronal and glial cells. The results raise the possibility thatT. cruzirecognition of TrkC underlies regenerative events in nervous tissues of patients with Chagas' disease.
Immunohistochemical analysis of the oxidative phosphorylation complexes in skeletal muscle from patients with mitochondrial DNA encoded tRNA gene defects
Authors: De Paepe B , Smet J , Lammens M , Seneca S , Martin J-J , De Bleecker J , De Meirleir L , Lissens W , Van Coster R 
Published: January 2009

Background:Mitochondrial diseases display a heterogeneous spectrum of clinical phenotypes and therefore the identification of the underlying gene defect is often a difficult task.Aims:To develop an immunohistochemical approach to stain skeletal muscle for the five multi-protein complexes that organise the oxidative phosphorylation (OXPHOS) in order to improve the diagnostic workup of mitochondrial defects.Methods:OXPHOS complexes were visualised in skeletal muscle tissue using antibodies directed against different subunits. The staining patterns of patients with heteroplasmic defects in mtDNA tRNA genes were compared with those of normal and disease controls.Results:Normal skeletal muscle displayed a checkerboard staining pattern for complexes I to V due to the higher mitochondrial content of slow muscle fibres versus fast fibres. In patients with tRNA defects, a much more heterogeneous staining pattern was observed for complex I (all six patients) and complex IV (4 of 6 patients): a mosaic staining pattern in which individual fibres displayed staining intensities that ranged from strong to negative. Ragged red fibres (RRFs) in patients with MERRF (myoclonic epilepsy and ragged red fibres) were all complex I and IV negative, while in patient with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) the majority of RRFs were complex I negative and complex IV positive.Conclusion:Immunohistochemical detection of OXPHOS complexes could represent a valuable additional diagnostic tool for the evaluation of mitochondrial cytopathy. The technique helps to detect heteroplasmic mtDNA defects. Staining for complex I in particular was able to identify two tRNA patients that stayed undetected with routine histochemical evaluation.
Healthcare professionals’ and researchers’ understanding of cancer genetics activities: a qualitative interview study: Table 1
Authors: Hallowell N , Cooke S , Crawford G , Parker M , Lucassen A 
Published: January 2009

Aims:To describe individuals’ perceptions of the activities that take place within the cancer genetics clinic, the relationships between these activities and how these relationships are sustained.Design:Qualitative interview study.Participants:Forty individuals involved in carrying out cancer genetics research in either a clinical (n = 28) or research-only (n = 12) capacity in the UK.Findings:Interviewees perceive research and clinical practice in the subspecialty of cancer genetics as interdependent. The boundary between research and clinical practice is described as vague or blurred, and this ambiguity is regarded as being sustained by a range of methodological, ethical and economic factors. The implications of these findings for the “therapeutic misconception” are explored. It is argued that while research participation is seen as having therapeutic benefit for individual patients, the interviewees are not labouring under any misconceptions about the relationship between research and clinical care. It is suggested that concepts such as the “therapeutic misconception” may have less relevance in highly technological specialities that are characterised by a developing evidence base.
Review of policies for injuries to research participants in India
Authors: Thatte U M , Kulkarni-Munshi R , Kalekar S A 
Published: January 2009

Background:As there is little Indian data about severity, frequency and types of research related injuries, costs involved and policies regarding compensation, this study was conducted to review the present Indian scenario.Methods:The study was carried out in three parts; a questionnaire-based survey, in-depth interviews, and a review of informed consent and insurance documents of projects submitted to three ethics committees.Results:47% of investigators were either unaware of, or had not understood, the legal requirements and depended on sponsors to manage these issues, whereas 74% of ethics committee members were aware of the requirements. Although 40% of investigators, 30% of ethics committee members and all sponsors had policies to manage compensation issues, these were mainly to provide immediate free medical care or reimbursement of expenses incurred for the acute management of an adverse event. Compensation for loss of time/wages, death, physical disability or long term incapacitation was not included. A review of informed consent and insurance documents showed that compensation issues were inadequately discussed, with only insurance certificates submitted to ethics committees.Conclusion:In India, there are no uniform policies and investigators are largely unaware of their responsibilities. Therefore, there is an urgent need to draft national guidelines regarding compensation for research injuries of research participants and highlight the responsibilities of each stakeholder. Potential research injuries should be categorised based on risk assessment, severity and seriousness of the injury. Further, it would be necessary to have arbitration committees to determine the extent of compensation. Training and awareness workshops for those involved in clinical research, including research participants, is also needed.
Predicting the future prevalence of cigarette smoking in Australia: how low can we go and by when?
Authors: Gartner C E , Barendregt J J , Hall W D 
Published: January 2009

Background:In Australia, smoking prevalence has declined in men since the 1950s and in women since the 1980s. Future smoking prevalence in Australia is predicted from estimates of previous and current age-specific and sex-specific cessation rates and smoking uptake in young people derived from national survey data on the prevalence of smoking between 1980 and 2007.Methods:A dynamic forecasting model was used to estimate future smoking prevalence in the Australian population based on a continuation of these current trends in smoking uptake and cessation.Results:The results suggest that Australia’s smoking prevalence will continue to fall while current rates of initiation and cessation are maintained. But a continuation of current smoking cessation and initiation patterns will see around 14% of adults still smoking in 2020.Conclusions:Smoking cessation rates will need to double for Australian smoking prevalence to reach a policy target of 10% by 2020.
Determining the post-glacial evolution of a northeast Pacific coastal fjord using a multiproxy geochemical approachThis article is one of a series of papers published in this Special Issue on the theme Polar Climate Stability Network.
Authors: Ivanochko Tara S. , Calvert Stephen E. , Southon John R. , Enkin Randolph J. , Baker Judith , Dallimore Audrey , Pedersen Thomas F. 
Published: January 2009

A 40.32 m piston core recovered from Effingham Inlet, on the west coast of Vancouver Island, provides the basis for a high-resolution geochemical study of the last deglaciation and the Holocene. Glacial retreat, basin isolation, sea-level rise, and productivity variations are determined using proxies for sediment composition (K/Al, Fe/Al, Mg/Al), grain size (Ti/Al, Zr/Al), sedimentary redox conditions (Mo/Al, U/Al), and productivity (wt.% organic carbon, wt.% opal). As local ice retreated and marine waters inundated the basin, coarse-grained glacimarine sediments were replaced by finer grained, laminated, opal-rich sediments. During meltwater pulse-1a, the dominance of local crustal rise over eustatic sea-level rise resulted in the progressive restriction of ocean circulation in Effingham Inlet and the formation of a temporary freshwater lake. The transition into stable Holocene conditions was initiated at ∼12 700 BP, which corresponds to the onset of the Younger Dryas, as identified by the Greenland Ice core Project (GRIP) ice core δ18O record and was completed by 10 700 BP, ∼800 years after the GRIP ice core record stabilized. Holocene Mo/Al and U/Al ratios range between 12–35 (×104) and 1–3.4 (×104), respectively, indicating that although large-amplitude, high-frequency fluctuations occur, the sediments of Effingham Inlet inner basin have remained organic rich and oxygen depleted for the entire Holocene period. The combination of anoxic bottom waters and a Holocene sedimentation rate of 217 cm/ka have preserved a high-resolution record of environmental change in the northeast Pacific over the last 11 000 years.
Impact of melting of the Laurentide Ice Sheet on sediments from the upper continental slope off southeastern Canada: evidence from Sm–Nd isotopesThis article is one of a series of papers published in this Special Issue on the themePolar Climate Stability Network.
Authors: Stevenson R. K. , Meng X. W. , Hillaire-Marcel C. 
Published: January 2009

We present new Sm–Nd isotope data for sediments from a core located on the continental slope of the St. Pierre Bank of Canada’s east coast. The Nd analyses indicate that the sediments were derived from two principal sources: the North American Shield that yields an average early Proterozoic isotopic signature and a younger Proterozoic signature attributed to Appalachian crustal sources. The Appalachian-sourced sediments predominated during the last glacial maximum (LGM) and were associated with low sedimentation rates (<30 cm/ka), with the exception of a strong North American Shield signature present in a detrital carbonate layer that corresponds to Heinrich Layer 1 (H1). The dominance of the Appalachian signature decreased subsequent to H1. The Appalachian signatures closely follow the distribution of sediments interpreted as locally derived glacial tills, while the North American Shield signatures follow the distribution of hemipelagic mud that was likely deposited by the Labrador Current. The Nd data are consistent with the persistence of the Wisconsinan Ice Sheet coverage of Newfoundland and the Grand Banks after the LGM, although the coverage began to wane prior to 12.5 ka as evidenced by the increasing influence of the Labrador Current. However, an increase in the Appalachian isotope signature at the close of the Younger Dryas event likely indicates the final melting of the ice sheet covering the Grand Banks and the Avalon Peninsula, and the initiation of the Labrador Current’s modern circulation pathway.
Low- and high-frequency climate variability in eastern Beringia during the past 25 000 yearsThis article is one of a series of papers published in this Special Issue on the theme Polar Climate Stability Network.
Authors: Viau A. E. , Gajewski K. , Sawada M. C. , Bunbury J. 
Published: January 2009

We present new temperature and precipitation reconstructions for the past 25 000 cal. years BP from across eastern Beringia based on a network of pollen diagrams, an updated modern pollen calibration database, and an improved methodology using the modern analogue technique (MAT). Time series show July temperatures were around 4 °C lower during full glacial and January temperatures were about 2 °C lower than present. Annual temperatures rose beginning around 16 000 cal. years BP, reaching a maximum around 12 000 cal. year BP. The warming was more rapid in southern Beringia. Annual precipitation varied by 250 mm during the past 25 000 cal. years BP. Maps of reconstructed precipitation patterns show increasingly drier conditions since 12 000 cal. years BP. that vary regionally, suggesting Holocene atmospheric circulation changes at multiple time and space scales. Orbitally forced seasonality changes during the late glacial and early Holocene resulted in reversed seasonal temperature reconstructions due to methodological constraints using the MAT and (or) non-analogue conditions. The magnitude of millennial-scale climate variability in this region was greater during the last glacial and late glacial periods than during the past 8000 years.
Postglacial evolution of a Pacific coastal fjord in British Columbia, Canada: interactions of sea-level change, crustal response, and environmental fluctuations — results from MONA core MD02-2494This article is one of a series of papers published in this Special Issue on the theme Polar Climate Stability Network.
Authors: Dallimore Audrey , Enkin Randolph J. , Pienitz Reinhard , Southon John R. , Baker Judith , Wright Cynthia A. , Pedersen Tom F. , Calvert Steve E. , Ivanochko Tara , Thomson Richard E. 
Published: January 2009

The sedimentary record in a 40.9 m giant (Calypso) piston core (MD02-2494) raised from the inner basin within Effingham Inlet, British Columbia, Canada, during the 2002 Marges Ouest Nord Américaines (MONA) campaign, spans from 14 360 14C years BP (17 300 calibrated calendar (cal.) years BP) to about nine centuries before present. The core archives changes in sedimentation and sea level immediately following deglaciation of the Late Wisconsin Fraser Glaciation, which peaked about 15 000 14C years BP. The presence of the Mazama Ash in the core anchors a detailed chronology based on 49 radiocarbon dates and seven Pleistocene paleomagnetic secular variation correlations. Diatom assemblages identify a marine–freshwater–marine transition in the basin, which occurred 11 630 14C years BP (13 500 cal. years BP). At this time, a bedrock sill, presently at 46 m depth, was briefly exposed as sea level fell and then rose again during isostatic crustal adjustments. These data constrain a new sea-level curve for the outer coast of Vancouver Island covering the past 12 000 14C years BP (14 000 cal. years BP), providing new information on the nature of deglaciation along the west coast of Canada and informing interpretations of regional paleoceanographic records and mantle viscosity models.
Palynological evidence of Holocene climate change in the eastern Arctic: a possible shift in the Arctic oscillation at the millennial time scaleThis article is one of a series of papers published in this Special Issue on the theme Polar Climate Stability Network.
Authors: Ledu David , Rochon André , de Vernal Anne , St-Onge Guillaume 
Published: January 2009

Dinocyst assemblages and the physical properties of two sediment cores collected in the easternmost part of the main axis of the Northwest Passage, Canadian Arctic Ocean (cores 2004-804-009 BC and 2004-804-009 PC, 74°11.2′N, 81°11.7′W) were used to reconstruct changes in sea-surface conditions and to characterize changes in the depositional environment. Core 2004-804-009 PC spans the last 12 180 calibrated (cal) years BP, with sedimentation rates ranging from 45 to 122 cm/ka. Quantitative estimates of sea-surface parameters reveal relatively large hydrographic variability at millennial time scale. Before 11 000 cal years BP, our records suggest terrigenous inputs related to the last deglaciation. Between 11 000 and 9600 cal years BP, harsh conditions prevailed with August sea-surface temperatures <2 °C and the dominance of heterotrophic taxa. This episode was followed by a gradual increase in the relative abundance of phototrophic taxa and the establishment of milder condition with sea-surface temperature (SST) reaching ∼2 °C ∼8300 cal years BP, possibly related to increased exchange between the Arctic Ocean and the North Atlantic Ocean. From 6000 cal years BP to the late Holocene, climate variability could be the results of changes in the synoptic-scale atmospheric pattern such as the Arctic oscillation.
Holocene fluctuations in Arctic sea-ice cover: dinocyst-based reconstructions for the eastern Chukchi SeaThis article is one of a series of papers published in this Special Issue on the theme Polar Climate Stability Network.GEOTOP Publication 2008-0023.
Authors: McKay J. L. , de Vernal A. , Hillaire-Marcel C. , Not C. , Polyak L. , Darby D. 
Published: January 2009

Cores from site HLY0501-05 on the Alaskan margin in the eastern Chukchi Sea were analyzed for their geochemical (organic carbon, δ13Corg, Corg/N, and CaCO3) and palynological (dinocyst, pollen, and spores) content to document oceanographic changes during the Holocene. The chronology of the cores was established from 210Pb dating of near-surface sediments and 14C dating of bivalve shells. The sediments span the last 9000 years, possibly more, but with a gap between the base of the trigger core and top of the piston core. Sedimentation rates are very high (∼156 cm/ka), allowing analyses with a decadal to centennial resolution. The data suggest a shift from a dominantly terrigenous to marine input from the early to late Holocene. Dinocyst assemblages are characterized by relatively high concentrations (600–7200 cysts/cm3) and high species diversity, allowing the use of the modern analogue technique for the reconstruction of sea-ice cover, summer temperature, and salinity. Results indicate a decrease in sea-ice cover and a corresponding, albeit much smaller, increase in summer sea-surface temperature over the past 9000 years. Superimposed on these long-term trends are millennial-scale fluctuations characterized by periods of low sea-ice and high sea-surface temperature and salinity that appear quasi-cyclic with a frequency of about one every 2500–3000 years. The results of this study clearly show that sea-ice cover in the western Arctic Ocean has varied throughout the Holocene. More importantly, there have been times when sea-ice cover was less extensive than at the end of the 20th century.
Holocene and Last Interglacial cloudiness in eastern Baffin Island, Arctic CanadaThis article is one of a series of papers published in this Special Issue on the themePolar Climate Stability Network.GEOTOP Publication 2008-0027.
Authors: Fréchette Bianca , de Vernal Anne , Richard Pierre J.H. 
Published: January 2009

This study presents Last Interglacial and Holocene vegetation and climate changes at Fog Lake (67°11′N, 63°15′W) on eastern Baffin Island, Arctic Canada. The vegetation cover is reported as vegetation structural types (or biomes). July air temperature and sunshine during the growing season (June–July–August–September) were reconstructed from pollen assemblages using the modern analogue technique. The vegetation of the Last Interglacial period evolved from a prostrate dwarf-shrub tundra to a low- and high-shrub tundra vegetation. The succession of four Arctic biomes was distinguished from the Last Interglacial sediments, whereas only one Arctic biome was recorded in the Holocene sediments. From ca. 8300 cal. years BP to present, hemiprostrate dwarf-shrub tundra occupied the soils around Fog Lake. During the Last Interglacial, growing season sunshine was higher than during the Holocene and July air temperature was 4 to 5 °C warmer than present. A principal component analysis helped in assessing relationship between floristic gradients and climate. The major vegetation changes through the Last Interglacial and Holocene were driven by July air temperature variations, whereas the minor, or subtle, vegetation changes seem rather correlated to September sunshine. This study demonstrates that growing season sunshine conditions can be reconstructed from Arctic pollen assemblages, thus providing information on feedbacks associated with cloud cover and summer temperatures, and therefore growing season length.