julilili42/papers huggingface dataset:
Non-Selective Cation Channel-Mediated Ca<sup>2+</sup>-Entry and Activation of Ca<sup>2+</sup>/Calmodulin-Dependent Kinase II Contribute to G<sub>2</sub>/M Cell Cycle Arrest and Survival of Irradiated Leukemia Cells
2010-01-01

Genotoxic stress induces cell cycle arrest and DNA repair which may enable tumor cells to survive radiation therapy. Here, we defined the role of Ca(2+) signaling in the cell cycle control and survival of chronic myeloid leukemia (CML) cells subjected to ionizing radiation (IR). To this end, K562 erythroid leukemia cells were irradiated (0-10 Gy). Tumor survival was analyzed by clonogenic survival assay and cell cycle progression via flow cytometry. Plasma membrane cation conductance was assessed by patch-clamp whole-cell recording and the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) was measured by fura-2 Ca(2+) imaging. Nuclear activity of Ca(2+)/calmodulin-dependent kinase II (CaMKII) was defined by Western blotting. In addition, the effect of IR (5 Gy) on the cation conductance of primary CML cells was determined. The results indicated that IR (10 Gy) induced a G(2)/M cell cycle arrest of K562 cells within 24 h post-irradiation (p.i.) and decreased the clonogenic survival to 0.5 % of that of the control cells. In K562 cells, G(2)/M cell cycle arrest was preceded by activation of TRPV5/6-like nonselective cation channels in the plasma membrane 1-5 h p.i., resulting in an elevated Ca(2+) entry as evident from fura-2 Ca(2+) imaging. Similarly, IR stimulated a Ca(2+)-permeable nonselective cation conductance in primary CML cells within 2-4 h p.i.. Ca(2+) entry, into K562 cells was paralleled by an IR-induced activation of nuclear CaMKII. The IR-stimulated accumulation in G(2) phase was delayed upon buffering [Ca(2+)](i) with the Ca(2+) chelator BAPTA-AM or inhibiting CaMKII with KN93 (1 nM). In addition, KN93 decreased the clonogenic survival of irradiated cells but not of control cells. In conclusion, the data suggest that IR-stimulated cation channel activation, Ca(2+) entry and CaMKII activity participate in control of cell cycle progression and survival of irradiated CML cells.
The stress response of the liver to physical exercise.
2010-01-01

Recent research on the effectiveness of training interventions indicates major alterations of hepatic lipid metabolism and suggests a substantial and beneficial adaptation of the liver to regular physical activity in humans. However, while various' data demonstrate the response of the working skeletal muscle to acute exercise and training, considerably less is known about the molecular events in the liver during and after increased physical activity. Here we discuss recent studies performed in rodents, that elucidate the acute hepatic response to one single bout of exercise with particular emphasis on stress response-related pathways. The acute transcriptional response to one exercise bout comprises three-times more hepatic transcripts than those expressed in soleus muscle, with a significantly more pronounced up- or downregulation of hepatic genes. Evaluation of the affected pathways shows that the liver responds to acute exercise with a rapid activation of the mitogen-activated protein kinase (MAPK) signalling pathway, of the p53 protein, and of interleukin (IL)-6-type cytokine signalling pathways, resulting in a marked transcriptional upregulation of stress response genes (e.g., transcription factors of the Fos/Jun-family, growth arrest and DNA damage (GADD)45gamma, and p53-target genes) and genes typically induced by energy depletion, e.g., insulin-like growth factor binding protein (IGFBP)-1, peroxisome proliferator-activated receptor coactivator (PGC)1alpha. One explanation for the marked differential expression of hepatic genes immediately after exercise is the induction of energetic stress. After non-exhaustive exercise energy depletion predominantly occurs in the liver not as much in the working muscle, and during exercise, the liver is exposed to altered concentrations of insulin and glucagon in the portal vein. Furthermore, lower plasma glucose levels post-exercise are related to increased expression levels of stress response genes. It appears that the unique function of the liver to supply glucose for the working muscle renders this organ especially susceptible for exercise-induced cellular stress that leads to the marked induction of defense adaptations. These results give rise to the question whether these molecular events are linked not only to stress defense but to the metabolic adaptations of the liver to exercise.
Easier When Done Than Said!
2010-01-01

Evidence for the criterion validity of indirect self-esteem measures is still limited, with only some studies finding effects of implicit (ISE) independent of explicit (ESE) self-esteem. This may be due to the fact that studies predicting actual behavior are particularly rare. The present study contributes evidence to the predictive validity of the Implicit Association Test and a recently developed self-judgment task under cognitive load. We used criteria beyond self-report: experimenter ratings of anxiety, linguistic aspects of anxiety, and spontaneous self-confident behaviors. Using paired criteria, we tested a double dissociation of ISE and ESE. Results supported our hypothesis: ISE predicted self-confident behaviors or aspects of anxiety that ESE was not able to predict, and vice versa. Thus, differential predictive validity of both measures of self-esteem was demonstrated. With behavioral criteria that tapped into impulsive processes, ISE was a better predictor than ESE was.
Amido-stabilized rare-earth metal mixed methyl methylidene complexes
2010-01-01

Donor(thf)-induced tetramethylaluminate cleavage of Ln(AlMe(4))(2)(NSiMe(3)Ar(iPr)) as well as the reaction of (LnMe(3))(n) (Ln = Y, Ho, Lu) with HNSiMe(3)Ar(iPr) in tetrahydrofuran affords unprecedented trinuclear rare-earth metal tetramethyl methylidene complexes which act as Schrock-type nucleophilic carbenes and methyl transfer agents.
Hyperactivity and Enhanced Curiosity of Mice Expressing PKB/SGK-resistant Glycogen Synthase Kinase-3 (GSK-3)
2010-01-01

The present observations disclose a significant role of PKB/SGK-dependent regulation of GSK-3 in the control of activity, anxiety and proneness to depression. Accordingly, mice expressing SGK/PKB resistant GSK-3 may be a valuable model of hyperactivity and mania.
Effect of Thymoquinone on Mouse Dendritic Cells
2010-01-01

Thymoquinone, a component of Nigella sativa is known to confer protection against tumour growth due to stimulation of tumour cell apoptosis. Moreover, thymoquinone has remarkable anti-inflammatory potency. Surprisingly, despite its powerful influence on inflammation and its immunomodulatory effects, little is known about its effect on dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. DC maturation and cytokine release is triggered by bacterial components such as lipopolysaccharides (LPS). The present study explored whether thymoquinone modifies LPS-induced DC maturation, survival and cytokine release. To this end, mouse bone marrow derived DCs were treated with LPS and different concentrations of thymoquinone and the surface expression of CD11c, CD86, MHCII, CD54 and CD40 was determined by FACS analysis, the formation of the interleukins 10 (IL-10) and 12 (IL-12p70) as well as TNF-alpha by ELISA, caspase activation by FITC-labelled antibodies (FACS), cell membrane scrambling by annexin V binding (FACS) and Akt and ERK1/2 phosphorylation by Western blotting. LPS increased the percentage of CD11c(+)CD86(+), CD11c(+)MHCII(+), CD11c(+)CD40(+) and CD11c(+)CD54(+) cells and stimulated the release of IL-10, IL-12p70 and TNF-alpha. These effects were blunted by thymoquinone in a concentration dependent manner (1-20 microM). Moreover, LPS decreased and thymoquinone increased caspase 3 and caspase 8 activation and annexin V binding. Moreover, LPS-induced phosphorylation of prosurvival kinases Akt and ERK1/2 was abrogated by thymoquinone. In conclusion, thymoquinone compromises the maturation, cytokine release and survival of DCs.
Constructing new Calabi-Yau 3-folds and their mirrors via conifold transitions
2010-01-01

We construct a surprisingly large class of new Calabi-Yau 3-folds X with small Picard numbers and propose a construction of their mirrors X * using smoothings of toric hypersurfaces with conifold singularities.These new examples are related to the previously known ones via conifold transitions.Our results generalize the mirror construction for Calabi-Yau complete intersections in Grassmannians and flag manifolds via toric degenerations.There exist exactly 198849 reflexive four-polytopes whose two-faces are only triangles or parallelograms of minimal volume.Every such polytope gives rise to a family of Calabi-Yau hypersurfaces with at worst conifold singularities.Using a criterion of Namikawa we found 30241 reflexive four-polytopes such that the corresponding Calabi-Yau hypersurfaces are smoothable by a flat deformation.In particular, we found 210 reflexive four-polytopes defining 68 topologically different
Fetal magnetoencephalography—achievements and challenges in the study of prenatal and early postnatal brain responses: a review
2010-01-01

Abstract Fetal magnetoencephalography (fMEG) is the only non‐invasive method for investigating evoked brain responses and spontaneous brain activity generated by the fetus in utero . Fetal auditory as well as visual‐evoked fields have been successfully recorded in basic stimulus–response studies. Moreover, paradigms investigating precursors for cognitive development, such as habituation and mismatch response have been applied successfully with fMEG. These and other studies have shown that the prenatal stage of life could be an important indicator for later cognitive development. This review addresses the achievements of fMEG and constructively discusses its challenges. It concludes with proposals for future studies as well as with designated new applications. Fetal MEG is a promising, and to date it is the only non‐invasive approach for the prenatal assessment of precursors for cognitive development. Future fMEG studies might even enable the diagnosis of developmental delays. Furthermore, fMEG could be critical for the implementation and evaluation of fetal intervention programmes in at‐risk populations. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Stimulation of Mouse Dendritic Cells by Gum Arabic
2010-01-01

Gum Arabic (GA), a nonabsorbable nutrient manufactured from the exudate of Acacia senegal, is composed of a complex polysaccharide. GA is used by the pharmaceutical and food industry as an emulsifier but may, at an appropriate dosage, modify intestinal transport. Dendritic cells (DCs) can protrude between epithelial cells and sense the composition of the lumen. As DCs are stimulated by bacterial polysaccharides, we hypothesized that GA may similarly stimulate DCs. To test that hypothesis, mouse DCs were treated with either LPS or GA and expression of maturation markers, phagocytotic activity, cytokine production and ability to stimulate CD4(+) T cells in allogenic mixed leukocyte reaction (allo-MLR) was analyzed. As a result both LPS and GA increased the percentage of CD11c(+)CD86(+), CD11c(+)MHCII(+), CD11c(+)CD40(+), CD54-expressing DCs and decreased their phagocytic activity. Both LPS and GA stimulated the production of IL-6, IL-10, IL12p70 and TNFalpha in a p38- and/or ERK-dependent manner. GA treatment led to an enhanced IL-10 secretion, whereas LPS was more effective on IL-6 and IL-12p70 production. Both LPS- and GA-stimulated DCs enhanced CD4(+) T cell proliferation but the profile of cytokines produced in allo-MLR was different. High levels of IL-10 and IL-6 were observed in the presence of GA-treated DCs, whereas IFN-gamma and IL-12p70 production was similar with LPS- or GA-treated DCs. LPS upregulated p38 and transiently ERK1/2, while GA led to more sustained activation of ERK1/2, only. In conclusion, the observations reveal a powerful immunomodulatory effect of GA.
Rivastigmine for the treatment of dementia in patients with progressive supranuclear palsy: Clinical observations as a basis for power calculations and safety analysis
2010-01-01

Cognitive decline and dementia are present in about 50% of patients with progressive supranuclear palsy (PSP). Based on the known involvement of the cholinergic system in PSP patients, and because rivastigmine, in contrast to other cholinesterase inhibitors, inhibits both acetylcholinesterase and butyrylcholinesterase, we discuss clinical observations of five patients suffering from PSP and dementia who were all treated with rivastigmine over a period of 3 to 6 months. We found a slight improvement in specific cognitive function that may justify further controlled studies. A calculation of sample size revealed that a study on the effect of rivastigmine in PSP should include about 31 patients to detect a significant effect. In subtests, meaningful results can be obtained with even lower numbers (five patients for a verbal fluency test, and 14 patients for a logical memory task).
Regulation of the Glutamate Transporter EAAT4 by PIKfyve
2010-01-01

The excitatory amino-acid transporter EAAT4 (SLC1A6), a Na(+),glutamate cotransporter expressed mainly in Purkinje cells, serves to clear glutamate from the synaptic cleft. EAAT4 activity is stimulated by the serum and glucocorticoid inducible kinase SGK1. SGK1-dependent regulation of the Na(+),glucose transporter SGLT1 (SLC5A1) and the creatine transporter CreaT (SLC6A8) has recently been shown to involve the mammalian phosphatidylinositol-3-phosphate-5-kinase PIKfyve (PIP5K3). The present experiments thus explored whether SGK1-dependent EAAT4-regulation similarly involves PIKfyve. In Xenopus oocytes expressing EAAT4, but not in water injected oocytes, glutamate induced a current which was significantly enhanced by coexpression of PIKfyve and SGK1. The glutamate induced current in Xenopus oocytes coexpressing EAAT4 and both, PIKfyve and SGK1, was significantly larger than the current in Xenopus oocytes expressing EAAT4 together with either kinase alone. Coexpression of the inactive SGK1 mutant (K127N)SGK1 did not significantly alter glutamate induced current in EAAT4-expressing Xenopus oocytes and abolished the stimulation of glutamate induced current by coexpression of PIKfyve. The stimulating effect of PIKfyve was abrogated by replacement of the serine with alanine in the SGK consensus sequence ((S318A)PIKfyve). Furthermore, coexpression of (S318A)PIKfyve significantly blunted the stimulating effect of SGK1 on EAAT4 activity. The observations disclose that PIKfyve indeed participates in the regulation of EAAT4.
Prospective Controlled Animal Study on Biopsy Sampling with New Flexible Cryoprobes versus Forceps: Evaluation of Biopsy Size, Histological Quality and Bleeding Risk
2010-01-01

&lt;i&gt;Background:&lt;/i&gt; Cryoextraction is a procedure used for the recanalization of obstructed airways caused by visible exophytic endobronchial tumor. Biopsy samples obtained by this technique have been shown to be useful for histological assessment. &lt;i&gt;Objectives:&lt;/i&gt; The aim of the present animal study was to systematically evaluate biopsy size, histological quality and bleeding risk after cryobiopsy with new, flexible cryoprobes in comparison with forceps biopsy, serving as the gold standard. &lt;i&gt;Methods:&lt;/i&gt; Biopsies were obtained from anesthetized pigs with the flexible bronchoscopy technique, and evaluated histologically with respect to their size and quality. Bleeding frequency, bleeding duration and histological changes in the biopsy bed were also recorded. &lt;i&gt;Results:&lt;/i&gt; Cryobiopsies were significantly larger than forceps biopsies. The size of cryobiopsies was dependent on the freezing time. The histological quality of the cryobiopsy specimenswas not impaired by the freezing process, whereas forceps biopsies showed typical crush artifacts. Despite the larger defects left in the tracheobronchial system after cryobiopsy, bleeding frequency and duration were not higher compared to forceps biopsy. &lt;i&gt;Conclusions:&lt;/i&gt; Since cryobiopsy sampling is not associated with a higher bleeding risk compared with forceps biopsy, this new biopsy technique offers – in addition to a good specimen quality – a safe and valuable tool with the potential of improving the outcome of diagnostic endoscopy.
Insulin Modulation of Magnetoencephalographic Resting State Dynamics in Lean and Obese Subjects
2010-01-01

Lean and obese subjects can exhibit differences in neuronal activity during resting state and tasks. Changes in hormonal status and their action related to increased body weight may be the determining factor for these differences. One prime candidate is insulin, which until recently was mainly related to its metabolic function for the transport and regulation of glucose in the periphery. However insulin also acts as an anorexic signal in the central nervous system contributing to the termination of food intake in the postprandial state. In our study, we examined with whole-head magnetoencephalography the effect of intranasal insulin on the dynamics of the resting state network in a placebo controlled study. Weighted clustering coefficient C, which describes local interconnectedness, and weighted path length L, a measure of global interconnectedness, were computed. These parameters showed high intraindividual reliability. However, no difference for the network dynamics was found between lean and obese subjects in the basal state. The application of insulin led to subject specific changes and we found a statistically significant positive correlation between the insulin induced change in path length in the theta band (4-8 Hz) and body mass index. The change in pathway length after insulin administration indicates a strong insulin modulation on global communication efficiency, which is probably related to the signaling between different regions involved in satiation and homeostatic control.
Functional Analysis of a Novel I71N Mutation in the <i>GJB2</i> Gene Among Southern Egyptians Causing Autosomal Recessive Hearing Loss
2010-01-01

Mutations in GJB2, a gene encoding the gap junction protein connexin 26 (Cx26), are a major cause for inherited and sporadic non-syndromic hearing loss, albeit with highly variable clinical effects. To determine new mutations and their frequencies in a Southern Egyptian population restriction fragment length polymorphism, gene sequencing, and single strand conformational polymorphism revealed only 2 mutations for GJB2: c.35delG and p.I71N. The allelic frequency of the c.35delG mutation was 8.7% (found in 27 out of 310 investigated alleles) resulting in a relatively low carrier frequency (1.6%) in Upper Egypt. The new mutation, a substitution of isoleucin (I) (a non-polar amino acid) by the polar amino acid asparagin (N), was localized within the conserved Cx26 structure. The functional significance of p.I71N was tested by injection of cRNA into Xenopus laevis oocytes. Cx26 hemi-channel activity was measured by depolarization activated conductance in non-coupled oocytes. As a result, the p.I71N mutated channel was non-functional. The study discloses a novel, functionally relevant GJB2 mutation and defines the contribution of Cx26 alterations to the hearing loss in the Southern Egyptian population.
Numerical simulations of microstructures using the Elle platform: A modern research and teaching tool
2010-01-01

The last 20 years have seen a manifold increase in the application of numerical simulations in the earth sciences. This contribution aims to provide an overview of the possibilities of using numerical techniques, in particular the numerical simulation package Elle, as an aid in the training for microstructural interpretation in rocks. Three sets of experiments are described to illustrate the range of simulations currently possible, investigating the effects of grain growth, polyphase deformation and dynamic recrystallisation. Numerical simulations of static annealing of a pre-deformed natural sample show that Crystallographic Preferred Orientations can still be used for the interpretation of kinematic and deformation conditions, even after substantial postdeformational annealing. However, the grain network characteristics such as grain size, grain size distribution, boundary shapes and aspect ratios are rapidly altered during annealing, especially if the grains possessed highly contrasting internal strain energies. Experiments modelling two and three phase viscous deformation show that the rheology and microstructural evolution of a rock is largely determined by the linearity or non-linearity of viscous deformation; whereas the number of phases with differing viscosity is less important. Variations in strain in the same mineral phases can be used to infer flow properties. The spatial distribution of phases significantly influences the rheology at a specific point in time. During dynamic recrystallization the rates of the competing processes of grain size reduction and increase can have a systematic influence on the evolution of grain characteristics. Relatively high rates of grain size increasing processes result in larger grain sizes, lower aspect ratios, stabilization of grain size at lower strain and less strain localization. Numerical simulations can help to answer field related questions and to identify the number of significant active processes. They are also extremely useful as teaching tools as processes can easily be turned on or off, parameters can be changed and boundary conditions altered. Fortunately, numerical simulations have now matured to a point where users that do not want to spend time in coding a model can still perform and analyse numerical simulations.
Evaluating dependency parsing performance on german learner language
2010-01-01

Ott, N. &amp; R. Ziai (2010). Evaluating dependency parsing performance on german learner language. In M. Dickinson, K. Müürisep &amp; M. Passarotti (eds.), Proceedings of the Ninth International Workshop on Treebanks and Linguistic Theories. Vol. 9 of NEALT Proceeding Series, 175–186.
Effect of Bacterial Lipopolysaccharide on Na<sup>+</sup>/H<sup>+</sup> Exchanger Activity in Dendritic Cells
2010-01-01

The function of dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity, is stimulated by bacterial lipopolysaccharides (LPS), which trigger the formation of reactive oxygen species (ROS). In macrophages, ROS formation is paralleled by activation of the Na(+)/H(+) exchanger, a carrier involved in the regulation of cytosolic pH and cell volume. The present study explored whether LPS influence Na(+)/H(+) exchanger activity in DCs. The DCs were isolated from murine bone marrow, cell volume was estimated from forward scatter in FACS analysis, ROS production from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, apoptosis from annexin V binding, cytosolic pH (pH(i)) from 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence and Na(+)/H(+) exchanger activity from the Na(+) dependent realkalinization following an ammonium pulse. Exposure of DCs to LPS (1 μg/ml) led to a transient increase of Na(+)/H(+) exchanger activity. Moreover, LPS increased forward scatter and ROS formation and decreased apoptosis. The NHE1 inhibitor cariporide (10 μM) virtually abrogated Na(+)/H(+) exchanger activity, inhibited LPS-induced cell swelling, blunted LPS-induced ROS formation and reversed the antiapoptotic effect of LPS. Na(+)/H(+) exchanger activity was stimulated by oxidative stress and LPS induced stimulation of NHE activity was abolished in presence of ROS chelators (Tempol, Tiron and Vitamin C). In conclusion, LPS treatment transiently upregulates the Na(+)/H(+) exchanger in DCs, an effect required for the effects of LPS on DC survival, cell volume and ROS formation.