julilili42/papers huggingface dataset:
The DGAT2 gene is a candidate for the dissociation between fatty liver and insulin resistance in humans
2008-11-04

The enzyme DGAT (acyl-CoA:diacylglycerol acyltransferase) catalyses the final step of triacylglycerol (triglyceride) synthesis. Mice overexpressing hepatic DGAT2 fed a high-fat diet develop fatty liver, but not insulin resistance, suggesting that DGAT2 induces a dissociation between fatty liver and insulin resistance. In the present study, we investigated whether such a phenotype also exists in humans. For this purpose, we determined the relationships between genetic variability in the DGAT2 gene with changes in liver fat and insulin sensitivity in 187 extensively phenotyped subjects during a lifestyle intervention programme with diet modification and an increase in physical activity. Changes in body fat composition [MR (magnetic resonance) tomography], liver fat and intramyocellular fat (1H-MR spectroscopy) and insulin sensitivity [OGTT (oral glucose tolerance test) and euglycaemic–hyperinsulinaemic clamp] were determined after 9 months of intervention. A change in insulin sensitivity correlated inversely with changes in total body fat, visceral fat, intramyocellular fat and liver fat (OGTT, all P&amp;lt;0.05; clamp, all P≤0.03). Changes in total body fat, visceral fat and intramyocellular fat were not different between the genotypes of the SNPs (single nucleotide polymorphisms) rs10899116 C&amp;gt;T and rs1944438 C&amp;gt;T (all P≥0.39) of the DGAT2 gene. However, individuals carrying two or one copies of the minor T allele of SNP rs1944438 had a smaller decrease in liver fat (−17±10 and −24±5%; values are means±S.E.M.) compared with subjects homozygous for the C allele (−39±7%; P=0.008). In contrast, changes in insulin sensitivity were not different among the genotypes (OGTT, P=0.76; clamp, P=0.53). In conclusion, our findings suggest that DGAT2 mediates the dissociation between fatty liver and insulin resistance in humans. This finding may be important in the prevention and treatment of insulin resistance and Type 2 diabetes in subjects with fatty liver.
Light responses in the mouse retina are prolonged upon targeted deletion of the HCN1 channel gene
2008-11-04

Abstract Hyperpolarization‐activated and cyclic nucleotide‐gated (HCN) channels contribute to pacemaker activity, and co‐determine the integrative behaviour of neurons and shape their response to synaptic stimulation. Four channel isoforms, HCN1–4, have been described in mammals. Recent studies showed particularly strong expression of HCN1 channels in rods and cones of the rat retina, suggesting that HCN1 channels are involved in the shaping of light responses in both types of photoreceptors. Therefore, the loss of HCN1 channels should lead to pronounced changes in light‐induced electrical responses under both scotopic and photopic conditions. This was tested using a mouse transgenic approach. We used immunohistochemistry and patch‐clamp recording to study the distribution of HCN1 channels in the mouse retina. HCN1 channels were strongly expressed in rod and cone photoreceptors, as well as in some bipolar, amacrine and ganglion cell types. In electroretinograms (ERGs) from animals in which the HCN1 channel gene had been knocked out, the b‐wave amplitudes were unaltered (scotopic conditions) or somewhat reduced (photopic conditions), whereas the duration of both scotopic and photopic ERG responses was strikingly prolonged. Our data suggest that in visual information processing, shortening and shaping of light responses by activation of HCN1 at the level of the photoreceptors is an important step in both scotopic and photopic pathways.
ChemInform Abstract: Arene Dicarboxylic Acid Esters
2008-11-04

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Brain–computer interface in paralysis
2008-11-05

Invasive and noninvasive BCIs using recordings from nerve cells, large neuronal pools such as electrocorticogram and electroencephalography, or blood flow based measures such as functional magnetic resonance imaging and near-infrared spectroscopy show potential for communication in locked-in syndrome and movement restoration in chronic stroke, but controlled phase III clinical trials with larger populations of severely disturbed patients are urgently needed.
Analysis of the precision and sensitivity to change of different approaches to assess cartilage loss by quantitative MRI in a longitudinal multicentre clinical trial in patients with knee osteoarthritis
2008-11-05

Abstract Introduction Cartilage thickness and volume loss measurements using quantitative magnetic resonance imaging (qMRI) are suggested to detect significant cartilage changes over short time intervals. We aimed to compare these two different approaches looking at the global knee and subregions, using data from an osteoarthritis (OA) multicentre randomised clinical trial. Methods Three hundred and fifty-five patients with symptomatic knee OA were recruited for a two-year, double-blind, randomised clinical trial evaluating the effect of 200 mg licofelone twice daily and 500 mg naproxen twice daily on cartilage loss, and 301 patients had baseline MRI. MRIs were performed at baseline, 6, 12 and 24 months. Cartilage volume and thickness in the global joint, medial and lateral compartments, and central weight-bearing subregions of the medial and lateral femoral condyles and tibial plateaus were analysed. Data were analysed for the mean value imputed for intent-to-treat (ITT-MVI) and statistical analyses were performed using two-sample Student's t-test. Results Cartilage mean thickness loss in the global joint, lateral and medial compartments, as well as in medial compartments stratified according to patients with or without meniscal extrusion, was significantly less in the licofelone compared with the naproxen group at 12 and 24 months. Interestingly, these data were similar to those found when using cartilage volume loss as an outcome. Although greater cartilage volume and mean thickness loss was seen in central weight-bearing subregions of the medial and lateral compartments compared with the whole compartment and also in patients with meniscal lesions/extrusion, suggesting good sensitivity to change, its high standard deviation precluded for the condyles a high statistical power and abrogated statistically significant differences between the treatment groups. Conclusions These data demonstrate that both the measurement of cartilage thickness and that of cartilage volume provide the same level of sensitivity to estimate cartilage loss in a clinical trial. However, the potential of gaining statistical power with the use of thickness/volume change in knee subregions as an outcome seems negated by high inter-patient variability. Moreover, there is no superiority in statistical power by selecting patients with meniscal extrusion.
Switching of vascular phenotypes within a murine breast cancer model induced by angiopoietin‐2
2008-11-05

Abstract Sustained growth of solid tumours can rely on both the formation of new and the co‐option of existing blood vessels. Current models suggest that binding of angiopoietin‐2 (Ang‐2) to its endothelial Tie2 receptor prevents receptor phosphorylation, destabilizes blood vessels, and promotes vascular permeability. In contrast, binding of angiopoietin‐1 (Ang‐1) induces Tie2 receptor activation and supports the formation of mature blood vessels covered by pericytes. Despite the intense research to decipher the role of angiopoietins during physiological neovascularization and tumour angiogenesis, a mechanistic understanding of angiopoietin function on vascular integrity and remodelling is still incomplete. We therefore assessed the vascular morphology of two mouse mammary carcinoma xenotransplants (M6378 and M6363) which differ in their natural angiopoietin expression. M6378 displayed Ang‐1 in tumour cells but no Ang‐2 in tumour endothelial cells in vivo . In contrast, M6363 tumours expressed Ang‐2 in the tumour vasculature, whereas no Ang‐1 expression was present in tumour cells. We stably transfected M6378 mouse mammary carcinoma cells with human Ang‐1 or Ang‐2 and investigated the consequences on the host vasculature, including ultrastructural morphology. Interestingly, M6378/Ang‐2 and M6363 tumours displayed a similar vascular morphology, with intratumoural haemorrhage and non‐functional and abnormal blood vessels. Pericyte loss was prominent in these tumours and was accompanied by increased endothelial cell apoptosis. Thus, overexpression of Ang‐2 converted the vascular phenotype of M6378 tumours into a phenotype similar to M6363 tumours. Our results support the hypothesis that Ang‐1/Tie2 signalling is essential for vessel stabilization and endothelial cell/pericyte interaction, and suggest that Ang‐2 is able to induce a switch of vascular phenotypes within tumours. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.
Variance of the SGK1 Gene Is Associated with Insulin Secretion in Different European Populations: Results from the TUEF, EUGENE2, and METSIM Studies
2008-11-05

The rs9402571 SGK genotype associates with increased insulin secretion in lean non-diabetic TUEF/EUGENE2 participants and with lower diabetes prevalence in METSIM. Our study in three independent European populations supports the conclusion that SGK variability affects diabetes risk.
Selection of a trioxaquine as an antimalarial drug candidate
2008-11-06

Trioxaquines are antimalarial agents based on hybrid structures with a dual mode of action. One of these molecules, PA1103/SAR116242, is highly active in vitro on several sensitive and resistant strains of Plasmodium falciparum at nanomolar concentrations (e.g., IC 50 value = 10 nM with FcM29, a chloroquine-resistant strain) and also on multidrug-resistant strains obtained from fresh patient isolates in Gabon. This molecule is very efficient by oral route with a complete cure of mice infected with chloroquine-sensitive or chloroquine-resistant strains of Plasmodia at 26–32 mg/kg. This compound is also highly effective in humanized mice infected with P. falciparum . Combined with a good drug profile (preliminary absorption, metabolism, and safety parameters), these data were favorable for the selection of this particular trioxaquine for development as drug candidate among 120 other active hybrid molecules.
Conversion of cropland into grassland: Implications for soil organic‐carbon stocks in two soils with different texture
2008-11-06

Abstract Soil organic‐carbon (SOC) stocks are expected to increase after conversion of cropland into grassland. Two adjacent cropland and grassland sites—one with a Vertisol with 23 y after conversion and one with an Arenosol 29 y after conversion—were sampled down to 60 cm depth. Concentrations of SOC and total nitrogen (N tot ) were measured before and after density fractionation in two light fractions and a mineral‐associated fraction with C adsorbed on mineral surfaces. For the soil profiles, SOC stocks and radiocarbon ( 14 C) concentrations of mineral associated C were determined. Carbon stocks and mineral‐associated SOC concentrations were increased in the upper 10 cm of the grassland soil compared to the cropland. This corresponded to the root‐biomass distribution, with 59% and 86% of the total root biomass at 0–5 cm soil depth of the grasslands. However, at the Arenosol site, at 10–20 cm depth, C in the mineral‐associated fraction was lost 29 y after the conversion into grassland. Over all, SOC stocks were not significantly different between grassland and cropland at both sites when the whole profile was taken into account. At the Arenosol site, the impact of land‐use conversion on SOC accumulation was limited by low total clay surface area available for C stabilization. Subsoil C (30–50 cm) at cropland of the Vertisol site comprised 32% of the total SOC stocks with high 14 C concentrations below the plowing horizon. We concluded that fresh C was effectively translocated into the subsoil. Thus, subsoil C has to be taken into account when land‐use change effects on SOC are assessed.
Proteinuria in mice expressing PKB/SGK-resistant GSK3
2008-11-06

SGK1 is critically important for mineralocorticoid/salt-induced glomerular injury. SGK1 inactivates GSK3, which downregulates Snail, a DNA-binding molecule repressing the transcription of nephrin, a protein critically important for the integrity of the glomerular slit membrane. PKB/SGK-dependent GSK regulation is disrupted in mice carrying a mutation, in which the serine in the SGK/PKB-phosphorylation consensus sequence is replaced by alanine. The present study explored whether PKB/SGK-dependent GSK3 regulation influences glomerular proteinuria. Gene-targeted knockin mice with mutated and thus PKB/SGK-resistant GSK3α,β ( gsk3 KI ) were compared with their wild-type littermates ( gsk3 WT ). gsk3 KI and gsk3 WT mice were implanted with DOCA release pellets and offered 1% saline as drinking water for 21 days. Under standard diet, tap water intake and absence of DOCA, urinary flow rate, glomerular filtration rate, and urinary albumin excretion were significantly larger and blood pressure was significantly higher in gsk3 KI than in gsk3 WT mice. Within 18 days, DOCA/salt treatment significantly increased fluid intake and urinary flow rate, urinary protein and albumin excretion, and blood pressure in both genotypes but the respective values were significantly higher in gsk3 KI than in gsk3 WT mice. Plasma albumin concentration was significantly lower in gsk3 KI than in gsk3 WT mice. Proteinuria was abrogated by lowering of blood pressure with α 1 -blocker prazosin (1 μg/g body wt) in 8-mo-old mice. According to immunofluorescence, nephrin at 3 and 8 mo and podocin expression at 3 mo were significantly lower in gsk3 KI than in gsk3 WT mice. After 18 days, DOCA/salt treatment renal glomerular sclerosis and tubulointerstitial damage were significantly more pronounced in gsk3 KI than in gsk3 WT mice. The observations reveal that disruption of PKB/SGK-dependent regulation of GSK3 leads to glomerular injury with proteinuria, which may at least partially be secondary to enhanced blood pressure.
An Arginine Switch in the Species B Adenovirus Knob Determines High-Affinity Engagement of Cellular Receptor CD46
2008-11-06

ABSTRACT Adenoviruses (Ads) are icosahedral, nonenveloped viruses with a double-stranded DNA genome. The 51 known Ad serotypes exhibit profound variations in cell tropism and disease types. The number of observed Ad infections is steadily increasing, sometimes leading to fatal outcomes even in healthy individuals. Species B Ads can cause kidney infections, hemorrhagic cystitis, and severe respiratory infections, and most of them use the membrane cofactor protein CD46 as a cellular receptor. The crystal structure of the human Ad type 11 (Ad11) knob complexed with CD46 is known; however, the determinants of CD46 binding in related species B Ads remain unclear. We report here a structural and functional analysis of the Ad11 knob, as well as the Ad7 and Ad14 knobs, which are closely related in sequence to the Ad11 knob but have altered CD46-binding properties. The comparison of the structures of the three knobs, which we determined at very high resolution, provides a platform for understanding these differences and allows us to propose a mechanism for productive high-affinity engagement of CD46. At the center of this mechanism is an Ad knob arginine that needs to switch its orientation in order to engage CD46 with high affinity. Quantum chemical calculations showed that the CD46-binding affinity of Ad11 is significantly higher than that of Ad7. Thus, while Ad7 and Ad14 also bind CD46, the affinity and kinetics of these interactions suggest that these Ads are unlikely to use CD46 productively. The proposed mechanism is likely to determine the receptor usage of all CD46-binding Ads.
Simultaneous HESS and Chandra observations of Sagitarius A$^{\\star}$ during an X-ray flare
2008-11-06

The rapidly varying (~10 min timescale) non-thermal X-ray emission observed from Sgr A implies that particle acceleration is occuring close to the event horizon of the supermassive black hole. The TeV γ-ray source HESS J1745-290 is coincident with Sgr A and may be closely related to its X-ray emission. Simultaneous X-ray and TeV observations are required to elucidate the relationship between these objects. We report on joint HESS/Chandra observations performed in July 2005, during which an X-ray flare was detected. Despite a factor of ≈9 increase in the X-ray flux of Sgr A, no evidence is found for an increase in the TeV γ-ray flux from this region. We find that an increase in the γ-ray flux of a factor of 2 or greater can be excluded at a confidence level of 99%. This finding disfavours scenarios in which the keV and TeV emission are associated with the same population of accelerated particles and in which the bulk of the γ-ray emission is produced within ~1014 cm (~100) of the supermassive black hole
ChemInform Abstract: Lactones
2008-11-07

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Formation of Spirocyclic Compounds from Heck Cyclizations Invoking Cyclic Enamides.
2008-11-07

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
New data on the late Neandertals: Direct dating of the Belgian Spy fossils
2008-11-10

Abstract In Eurasia, the period between 40,000 and 30,000 BP saw the replacement of Neandertals by anatomically modern humans (AMH) during and after the Middle to Upper Paleolithic transition. The human fossil record for this period is very poorly defined with no overlap between Neandertals and AMH on the basis of direct dates. Four new 14 C dates were obtained on the two adult Neandertals from Spy (Belgium). The results show that Neandertals survived to at least ≈36,000 BP in Belgium and that the Spy fossils may be associated to the Lincombian–Ranisian–Jerzmanowician, a transitional techno‐complex defined in northwest Europe and recognized in the Spy collections. The new data suggest that hypotheses other than Neandertal acculturation by AMH may be considered in this part of Europe. Am J Phys Anthropol, 2009. © 2008 Wiley‐Liss, Inc.
Isolation of three stem cell lines from human sacrococcygeal teratomas
2008-11-10

Abstract Sacrococcygeal teratomas (SCTs) are benign tumours of the newborn with absolute indication for surgery directly after birth. We recently described the presence of stem cells positive for the stem cell markers nanog and Oct4 in SCTs. Here we report the isolation of three stem cell lines from three different SCTs. Cells were propagated in mesenchymal or in embryonic stem cell medium. Non‐clonal homogeneous stem cell lines were obtained after two to three passages and characterized in vitro by immunocytochemistry, RT‐PCR, western blot, FACS analysis, and metaphase spreads. The differentiation potential was tested in vitro and in vivo . The isolated cell lines, which we refer to as human sacrococcygeal teratoma stem cells (hSctSCs), express nanog, Oct4 and stella, and are negative for malignancy markers alpha‐fetoprotein and carcinoembryonic antigen. They can be induced in vitro to express neuronal, osteogenic, and chondrogenic traits. After grafting in vivo , spontaneous integration into the neural crest of the chick embryo and teratoma formation in the nude mouse were obtained. Our results indicate that SCTs are derived from remnants of the epiblast‐derived primitive streak, which in the human embryo normally regresses but forms teratomas in children affected with SCT. The hSctSCs therefore may be comparable to mouse epiblast‐derived stem cells (EpiSCs) and share characteristic features with human embryonic stem (hES) cells. Thus, SCT tissue obtained after surgery appears to be a novel source for the generation of human stem cells without the ethical implications associated with hES cells. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.
Taxonomy and Phylogeny of the Downy Mildews (Peronosporaceae)
2008-11-10

This chapter contains sections titled: Downy Mildew Taxonomy The Phylogeny and Taxonomy of the Peronosporaceae Species Concepts in Downy Mildews—Or the Philosophy of Lumping Versus Splitting The Brassicolous Downy Mildews The DMPHs The Downy Mildews with Colored Conidia The GDMs with Lasting Sporangiophores Genera of Unresolved Phylogenetic Position Future Perspectives Acknowledgments References Appendix
Efficacy of rotary instruments with greater taper in preparing oval root canals
2008-11-11

Abstract Aim To compare the preparation quality of two rotary systems and NiTi‐hand files in oval root canals, and to evaluate the effect of canal dimensions on the preparation. Methodology Ninety roots with oval root canals were selected. The middle third was cross sectioned at two levels and photographed. The maximum and minimum diameters of the root and canal were recorded. Teeth were distributed in three groups ( n = 30) using stratified randomization, and prepared under simulated clinical conditions with Mtwo, ProTaper, or NiTi‐hand files. The pre‐ and post‐preparation photographs were traced and superimposed, the thickness of dentine removed was measured and the ratio of prepared canal outline was calculated. The impact of preparation system and canal dimensions on the quality of the preparation was evaluated using regression analysis. Results With regards to the ratio of prepared canal outline, no statistical significant difference was found between Mtwo (0.75 [95%CI: 0.69; 0.81]) and ProTaper (0.75 [95%CI: 0.69; 0.80]), but both systems performed significantly better than NiTi‐hand files (0.65 [95%CI: 0.60; 0.71]). In six root canals in Mtwo‐group (20%), and eight root canals in ProTaper‐group (27%), the minimal thickness of dentine‐wall after preparation was less than 0.5 mm. In contrast to the maximum diameter of the root canal, the minimum diameter influenced the quality of the preparation ( P = 0.0006). Conclusions No instrumentation technique was able to circumferentially prepare the oval outline of root canals. Nevertheless, instruments with greater taper (ProTaper and Mtwo) were more efficient than NiTi‐ hand files, but this was, in some cases, at the expense of remaining dentine‐wall thickness.