julilili42/papers huggingface dataset:
Isotope fractionation between dissolved and suspended particulate Fe in the oxic and anoxic water column of the Baltic Sea
2013-01-15

Abstract. Fe isotope ratios and concentrations of dissolved Fe (Fedis, &lt; 0.45 μm) and of suspended particulate Fe (FeSPM) were analyzed from a depth profile through the anoxic Eastern Gotland Basin water column, Baltic Sea. Results show a sharp gradient in δ56Fedis across the ferruginous layer with δ56Fedis = −0.4‰ in the euxinic deep basin and δ56Fedis = &amp;amp;plus;0.3‰ in the oxic upper water column. The isotopic gradient overlaps with a strong concentration gradient of Fedis, a concentration maximum in FeSPM and lower δ56FeSPM values than δ56Fedis. These features indicate preferential loss of light Fe isotopes from solution to suspended iron-oxyhydroxides (FeIOH) during typical oxidative precipitation across the redox interface. The sign of the overall fractionation, Δ56FeIOH-Fe(II)(aq) &lt; 0‰, is in contrast to similar, mostly non-marine redox environments, where Δ56FeIOH-Fe(II)(aq) &gt; 0‰. The difference appears to be the result of isotope exchange dominated by reaction kinetics in the marine water column, rather than equilibrium fractionation generally inferred for oxidative Fe precipitation elsewhere. High residual δ56Fedis immediately above the oxic–ferruginous interface and throughout the oxic water column suggests that any potential dissolved Fe export from marine reducing waters into the oxic open water column is enriched in the heavy isotopes. In the deep, mildly euxinic water column above the level of Fe sulfide saturation, a decreasing δ56FeSPM trend with depth and a generally low δ56Fedis are comparable to trends generally observed in marine anoxic sediment profiles where microbial reductive Fe dissolution occurs. The isotope composition of the redox-cycled Fe inventory in anoxic marine basins mainly reflects the balance between external fluxes, driving the composition towards crustal δ56Fe values, and intensity of internal recycling, driving δ56Fe towards negative values.
Sex Differences in the Processing of Global vs. Local Stimulus Aspects in a Two-Digit Number Comparison Task – An fMRI Study
2013-01-15

It has been debated for several decades, whether number magnitudes are processed global/holistically (whole number magnitudes) or in a local/decomposed fashion (digit magnitudes). However, while it has been suggested that men attend stronger to the global level, while women attend stronger to the local level, the question has never been studied with regards to sex differences. In two-digit number comparison men should engage a more holistic processing strategy, while women should engage a more decomposed strategy. To test this hypothesis, we employed number comparison stimuli of varying decade crossing and unit-decade compatibility in men (n = 16) and women (n = 16) during their early follicular and mid-luteal cycle phase. In within-decade (WD) items both numbers had the same decade digits. Non-WD items were unit-decade-compatible, if the smaller number contained the smaller unit-digit and incompatible otherwise. In incompatible items the two local features require different responses. Thus, processing of the local level should result in a compatibility effect in RT and recruitment of differential neural networks for compatible and incompatible items. The results support the view of a holistic strategy in men and a decomposed strategy in women. In men RT and BOLD-response did not differ for incompatible compared to compatible items. Women respond slower to incompatible compared to compatible items. They show a BOLD-response compatibility effect in regions of the default mode network during their follicular phase and in prefrontal areas involved in inhibitory control during their luteal phase. Furthermore, lateralization indices interacted with decade crossing and menstrual cycle phase in a way consistent with the hypothesis of progesterone-mediated interhemispheric decoupling.
Lewis Ayres,Augustine and the Trinity
2013-01-15

This is an impressive work. It is not a book just about Augustine's work ‘On the Trinity’, but on Augustine's trinitarian thought as a whole. It is a mature work, not written within a couple of months, but with years of thinking and rethinking. All this time has helped make the book what it is. I am pleased that it is a historical work, mainly for two reasons: (a) it sketches the development of Augustine's thought (this old model of German historical approach is always helpful), and (b) it places Augustine's trinitarian thought in a specific place in the history of theology. Of course, there are warnings in the Introduction that the book has neither the aim to offer a complete ‘history of Augustine's Trinitarian thought’ nor does it set out to be a monograph about the whole of De trinitate . In fact, the monograph starts with the early Augustine, sketching the ‘origins’ of his trinitarian thought, and the chapters about De trinitate intend to set out the fundamental lines of Augustine's thought in De trinitate . So I think we are allowed to read this book as a new approach to an old problem: how did Augustine's trinitarian thought develop into the mature form found in De trinitate ? If we follow Ayres’ approach, three problems appear. I ask: (a) what about philosophy, (b) what about Manichaeism and (c) what kind of theology is regarded as the background to Augustine's trinitarian thought?
Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation
2013-01-16

Cytochromes P450 (CYP) are a major source of variability in drug pharmacokinetics and response. Of 57 putatively functional human CYPs only about a dozen enzymes, belonging to the CYP1, 2, and 3 families, are responsible for the biotransformation of most foreign substances including 70-80% of all drugs in clinical use. The highest expressed forms in liver are CYPs 3A4, 2C9, 2C8, 2E1, and 1A2, while 2A6, 2D6, 2B6, 2C19 and 3A5 are less abundant and CYPs 2J2, 1A1, and 1B1 are mainly expressed extrahepatically. Expression of each CYP is influenced by a unique combination of mechanisms and factors including genetic polymorphisms, induction by xenobiotics, regulation by cytokines, hormones and during disease states, as well as sex, age, and others. Multiallelic genetic polymorphisms, which strongly depend on ethnicity, play a major role for the function of CYPs 2D6, 2C19, 2C9, 2B6, 3A5 and 2A6, and lead to distinct pharmacogenetic phenotypes termed as poor, intermediate, extensive, and ultrarapid metabolizers. For these CYPs, the evidence for clinical significance regarding adverse drug reactions (ADRs), drug efficacy and dose requirement is rapidly growing. Polymorphisms in CYPs 1A1, 1A2, 2C8, 2E1, 2J2, and 3A4 are generally less predictive, but new data on CYP3A4 show that predictive variants exist and that additional variants in regulatory genes or in NADPH:cytochrome P450 oxidoreductase (POR) can have an influence. Here we review the recent progress on drug metabolism activity profiles, interindividual variability and regulation of expression, and the functional and clinical impact of genetic variation in drug metabolizing P450s.
High Cut-Off Renal Replacement Therapy for Removal of Myoglobin in Severe Rhabdomyolysis and Acute Kidney Injury: A Case Series
2013-01-16

&lt;b&gt;&lt;i&gt;Background/Aim:&lt;/i&gt;&lt;/b&gt; Rhabdomyolysis is associated with the release of myoglobin into the circulation, promoting acute kidney injury (AKI). In severe rhabdomyolysis, dialysis-dependent AKI doubles mortality. Standard blood purification techniques have limited efficacy in removing myoglobin. We describe high cut-off (HCO) renal replacement therapy (RRT) as a novel approach for extracorporeal elimination of myoglobin in rhabdomyolysis-associated AKI. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; With an in vivo molecular cut-off at 45 kDa, HCO filters are effective in removing myoglobin (17.8 kDa). Clearances across standard and HCO filters using continuous or intermittent RRT are reviewed in a case series of 11 patients with severe rhabdomyolysis and dialysis-dependent AKI. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Median myoglobin clearance across standard high-flux filters was 3.3 (interquartile range 2.3–3.9) ml/min for sustained low-efficiency daily dialysis (SLEDD) batch hemodialysis (HD) and 3.7 (2.9–6.7) ml/min for conventional HD. Respective clearances using HCO filters (membrane surface area: 1.1 m&lt;sup&gt;2&lt;/sup&gt;) were 21.7 (20.3–26.1) ml/min (SLEDD) and 44.2 (41.3–47.0) ml/min (HD). Corrected for filter size, up to 20-fold higher clearances were obtained using HCO filters, resulting in profound and sustained reduction of plasma myoglobin concentration. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; As a novel approach, HCO RRT allows for rapid and effective removal of myoglobin from the circulation. In light of the pathogenic role in AKI, reducing exposure of the kidney to myoglobin may improve renal recovery and patient outcome. Our data pave the way for prospective trials, addressing this issue.
Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update
2013-01-17

The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Methyltransferase Genotype and Thiopurine Dosing was originally published in March 2011. We reviewed recent literature and concluded that although relevant new evidence has been generated, none of the evidence would change the primary dosing recommendations in the original guideline; therefore, the original publication remains clinically current. Up-to-date information on thiopurine methyltransferase (TPMT) gene alleles and nomenclature can be found at PharmGKB (http://www.pharmgkb.org). Clinical Pharmacology & Therapeutics (2013); 93 4, 324–325. doi:10.1038/clpt.2013.4
Pathogen-Triggered Activation of Plasmacytoid Dendritic Cells Induces IL-10–Producing B Cells in Response to Staphylococcus aureus
2013-01-17

Abstract Induction of polyclonal B cell activation is a phenomenon observed in many types of infection, but its immunological relevance is unclear. In this study we show that staphylococcal protein A induces T cell–independent human B cell proliferation by enabling uptake of TLR-stimulating nucleic acids via the VH3+ BCR. We further demonstrate that Staphylococcus aureus strains with high surface protein A expression concomitantly trigger activation of human plasmacytoid dendritic cells (pDC). Sensitivity to chloroquine, cathepsin B inhibition, and a G-rich inhibitory oligodeoxynucleotide supports the involvement of TLR9 in this context. We then identify pDC as essential cellular mediators of B cell proliferation and Ig production in response to surface protein A–bearing S. aureus. The in vivo relevancy of these findings is confirmed in a human PBMC Nod/scidPrkdc/γc−/− mouse model. Finally, we demonstrate that co-operation of pDC and B cells enhances B cell–derived IL-10 production, a cytokine associated with immunosuppression and induction of IgG4, an isotype frequently dominating the IgG response to S. aureus. IL-10 release is partially dependent on TLR2-active lipoproteins, a hallmark of the Staphylococcus species. Collectively, our data suggest that S. aureus exploits pDC and TLR to establish B cell–mediated immune tolerance.
Cross-language activation in same-script and different-script trilinguals
2013-01-17

In a picture naming study, we examined cross-language activation during speech production in three groups of trilinguals: L3-immersed German–English–Dutch, non-L3-immersed Dutch–English–German, and L3-immersed Russian–English–German trilinguals. All trilinguals named pictures with cognate and non-cognate names in their L2 and their L3. Specifically, we examined cognate effects in same-script trilinguals who were either immersed or not immersed in their L3 and trilinguals whose first language (Russian) differs in script from their other two languages (German, English) to address the questions (1) whether, as non-target language knowledge is co-activated, cognate effects accrue across languages during word production, and (2) whether immersion in L3 is a modulating factor in cross-language activation. We found cognate facilitation in the same-script trilinguals across all languages, although with patterns modulated by the trilinguals’ L3-immersion status and L3 proficiency, corroborating and extending earlier findings in bilingual adults and children. Critically, we also found cognate effects in the different-script trilinguals when the pictures had cognate names in all three languages, indicating that the L1 Russian phonology was activated during naming in L2 English when L3 German was also present, and vice versa.
Biomarkers for PD
2013-01-17

By the time patients present with motor symptoms of Parkinson disease (PD), two-thirds of their dopaminergic neurons will have died and at least some of the remaining dopaminergic neurons may already be affected by the molecular mechanisms that will eventually lead to their death. It is plausible to assume that any neuroprotective therapy for PD might be much more effective if individuals at risk could be started on such therapy while they are still in the premotor stage of the disease. Excellent epidemiologic combined with long-time clinical follow-up studies have unequivocally established that individuals with common but nonspecific symptoms, such as autonomic dysfunction including constipation, erectile and urinary dysfunction, and neuropsychiatric symptoms like depression or hyposmia, are at increased risk of developing PD.1 Other premotor manifestations of PD, in particular REM sleep behavioral disorder (RBD), are much more characteristic for premotor PD, but comparatively rare. Any attempt to base the identification of premotor PD on clinical observation only is therefore limited by low specificity (as would be the case for constipation) or sensitivity (as for RBD). Moreover, low specificity of some markers alludes to another major drawback in the search of biomarkers: the heterogeneity of PD. To evaluate markers reliably, it is therefore important to assess cohorts in whom homogenous pathogenesis can be assumed. This is the case in individuals who share the same genetically determined risk. Monogenetic forms of PD are, however, rare, and it is therefore difficult to recruit such genetically determined cohorts.
Reactive oxygen species delay control of lymphocytic choriomeningitis virus
2013-01-18

Cluster of differentiation (CD)8(+) T cells are like a double edged sword during chronic viral infections because they not only promote virus elimination but also induce virus-mediated immunopathology. Elevated levels of reactive oxygen species (ROS) have been reported during virus infections. However, the role of ROS in T-cell-mediated immunopathology remains unclear. Here we used the murine lymphocytic choriomeningitis virus to explore the role of ROS during the processes of virus elimination and induction of immunopathology. We found that virus infection led to elevated levels of ROS producing granulocytes and macrophages in virus-infected liver and spleen tissues that were triggered by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Lack of the regulatory subunit p47phox of the NADPH oxidase diminished ROS production in these cells. While CD8(+) T cells exhibited ROS production that was independent of NADPH oxidase expression, survival and T-cell function was elevated in p47phox-deficient (Ncf1(-/-)) mice. In the absence of p47phox, enhanced T-cell immunity promoted virus elimination and blunted corresponding immunopathology. In conclusion, we find that NADPH-mediated production of ROS critically impairs the immune response, impacting elimination of virus and outcome of liver cell damage.
Differentiation between idiopathic and atypical parkinsonian syndromes using three-dimensional magnetic resonance spectroscopic imaging
2013-01-18

Typical reversed rostral to caudal NAA/Cr ratios in iPD patients suggests that they could be linked to specific pathology of neuronal loss in the SN pars compacta. Therefore, the results suggest that MRSI may support the differential diagnosis of patients with clinically unclassifiable parkinsonian syndromes who do not yet fulfil the established clinical criteria.
<i>In vitro</i> evaluation of antiplasmodial activity of extracts of <i>Acanthospermum hispidum</i> dc (Asteraceae) and <i>Ficus thonningii</i> blume (moraceae), two plants used in traditional medicine in the republic of Congo
2013-01-18

The aim of this study was to evaluate extracts from two medicinal plants, Acanthospermum hispidum and Ficus thonningii, used in traditional medicine in Congo Brazzaville, for in vitro antiplasmodial activities against two laboratory strains of Plasmodium falciparum: the chloroquine sensitive 3D7 and the chloroquine resistant Dd2. ELISA HRP2 assay was used to evaluate the in vitro inhibitory activity of the extracts alone or in combination with chloroquine. Cytotoxicity was assessed on human HeLa cell line and reflected by the selectivity index. Methanolic extract of Acanthospermum hispidum exhibited a strong and a moderate inhibitory activity on the growth of Dd2 and 3D7 at 2.8 μg/ml and 9.2 μg/ml concentrations respectively with a selectivity index >10. The combination of the most active extract (methanolic extract of Acanthospermum hispidum) with chloroquine showed a synergistic interaction on both strains. The good selectivity index of Acanthospermum hispidum on HeLa cells reflects the safety of this plant. Extracts from Ficus thonningii did not show any promising antiplasmodial activity on both 3D7 and Dd2. Except the methanolic extract which exhibited a slight antiplasmodial activity with inhibitory concentration and selectivity index corresponding to 9.61 μg/ml and 11.16 respectively. Methanolic extract of Acanthospermum hispidum exhibited moderate to high inhibitory activity on 3D7 and Dd2 laboratory strains and a synergistic antimalarial effect when combined with chloroquine. Ficus thonningii seems to have no antimalarial activity. Phytochemical analysis, in vivo investigations using animal models and later clinical trials in collaboration with traditional practitioners are necessary to clarify the potential antimalarial activity of both plants.
Identifying a species tree subject to random lateral gene transfer
2013-01-20

A major problem for inferring species trees from gene trees is that evolutionary processes can sometimes favor gene tree topologies that conflict with an underlying species tree. In the case of incomplete lineage sorting, this phenomenon has recently been well-studied, and some elegant solutions for species tree reconstruction have been proposed. One particularly simple and statistically consistent estimator of the species tree under incomplete lineage sorting is to combine three-taxon analyses, which are phylogenetically robust to incomplete lineage sorting. In this paper, we consider whether such an approach will also work under lateral gene transfer (LGT). By providing an exact analysis of some cases of this model, we show that there is a zone of inconsistency when majority-rule three-taxon gene trees are used to reconstruct species trees under LGT. However, a triplet-based approach will consistently reconstruct a species tree under models of LGT, provided that the expected number of LGT transfers is not too high. Our analysis involves a novel connection between the LGT problem and random walks on cyclic graphs. We have implemented a procedure for reconstructing trees subject to LGT or lineage sorting in settings where taxon coverage may be patchy and illustrate its use on two sample data sets.
PTMeta: Increasing identification rates of modified peptides using modification prescanning and meta‐analysis
2013-01-20

The analysis of peptides and proteins in complex biological systems has greatly improved over the last decade. State‐of‐the‐art mass spectrometric instruments combined with adequate software tools allow for more and more comprehensive proteome analyses. Most proteome‐wide studies focus on the analysis of unmodified proteins or look at selected modifications only. However, spectral information of protein modifications, chemically induced through sample preparation or post‐translationally attached in biological pathways is acquired as a significant, yet disregarded, fraction of tandem spectra in most discovery studies. We present a new computational pipeline, PTMeta, to uncover information of modifications attached to peptides. We use modification prescanning to pinpoint the most abundant potential modifications, followed by extensive database search and a statistical framework to combine results from database search runs with different modification settings.
Food‐related impulsivity in obesity and Binge Eating Disorder – a systematic review
2013-01-21

Summary Impulsivity towards food has been recognized as a potential factor leading to increased food intake in obesity. Patients suffering from binge eating disorder ( BED ) form a specific subgroup of obese people that might be characterized by increased impulsivity. These assumptions, although, have yet to be verified. Therefore, this review evaluates evidence for food‐related impulsivity in obese people with and without BED and examines possible differences between both populations. More precisely, evidence for the two components of impulsivity is analyzed separately: evidence for reward sensitivity, specifically, the urge for appetitive stimuli and evidence for rash‐spontaneous behaviour such as acting disinhibited with no regard for the consequences. Our search resulted in 51 articles demonstrating generally increased food‐related impulsivity. We found particular emphasis on increased reward sensitivity in obese people, which appeared to be more pronounced in people with BED . There was little and conflicting evidence, however, concerning increased rash‐spontaneous behaviour in obese people without BED , but consistent evidence of an increase in obese people with BED . All in all, the evidence supports the view that BED represents a specific phenotype of obesity with increased food‐related impulsivity. Taking these specific deficits into account can enhance the effectiveness of weight reduction programmes and psychotherapy.