gebhart/patrepeval huggingface dataset:
Inhibition of Glycogen-synthase Kinase 3 Stimulates Glycogen Synthase and Glucose Transport by Distinct Mechanisms in 3T3-L1 Adipocytes (2000)

The role of glycogen-synthase kinase 3 (GSK3) in insulin-stimulated glucose transport and glycogen synthase activation was investigated in 3T3-L1 adipocytes. GSK3 protein was clearly present in adipocytes and was found to be more abundant than in muscle and liver cell lines. The selective GSK3 inhibitor, LiCl, stimulated glucose transport and glycogen synthase activity (20 and 65%, respectively, of the maximal (1 microm) insulin response) and potentiated the responses to a submaximal concentration (1 nm) of insulin. LiCl- and insulin-stimulated glucose transport were abolished by the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, wortmannin; however, LiCl stimulation of glycogen synthase was not. In contrast to the rapid stimulation of glucose transport by insulin, transport stimulated by LiCl increased gradually over 3-5 h reaching 40% of the maximal insulin-stimulated level. Both LiCl- and insulin-stimulated glycogen synthase activity were maximal at 25 min. However, insulin-stimulated glycogen synthase activity returned to basal after 2 h, coincident with reactivation of GSK3. After a 2-h exposure to insulin, glycogen synthase was refractory to restimulation with insulin, indicating selective desensitization of this pathway. However, LiCl could partially stimulate glycogen synthase in desensitized cells. Furthermore, coincubation with LiCl during the 2 h exposure to insulin completely blocked desensitization of glycogen synthase activity. In summary, inhibition of GSK3 by LiCl: 1) stimulated glycogen synthase activity directly and independently of PI3-kinase, 2) stimulated glucose transport at a point upstream of PI3-kinase, 3) stimulated glycogen synthase activity in desensitized cells, and 4) prevented desensitization of glycogen synthase due to chronic insulin treatment. These data are consistent with GSK3 playing a central role in the regulation of glycogen synthase activity and a contributing factor in the regulation of glucose transport in 3T3-L1 adipocytes.
A technique for the computation of sound radiation by vibrating bodies using multipole substitute sources (2005)

International audience
Tissue-Engineered Three-Dimensional In Vitro Models for Normal and Diseased Kidney (2010)

Morphogenesis of epithelial cells involves processes by which kidney shape and function are regulated. The lack of in vitro models that are sustainable for longer time periods and emulating complex intercellular interactions of the kidney have limited understanding about epithelial tissue morphogenesis and its aberrations in diseases such as autosomal dominant polycystic kidney disease (ADPKD). A sustainable three-dimensional (3D) coculture system for normal and diseased kidney tissues is reported here. Tubule- and ADPKD cyst-derived cells were cultured in extracellular matrix molecules infused into 3D porous silk scaffolds, and these cultures were subsequently extended into a perfusion bioreactor. The results indicated collagen-matrigel-mediated morphogenesis for both (normal and disease) cell types and also supported coculturing with fibroblasts. The structural and functional features of the kidney-like tissue structures were validated based on the distribution of E-cadherin, N-cadherin, Na+ K+ ATPase pump, and cellular uptake of the organic anion (6-carboxy fluorescein). Further, the structures were sustained for longer time periods using a perfusion bioreactor to demonstrate the potential utility of this 3D in vitro coculture system for ADPKD research, other epithelial tissue systems, and for in vitro drug screening.
[The inhibitory effect of total flavonoids of hippophae on the activation of NF-kappa B by stretching cultured cardiac myocytes]. (2003)

The results supported that the blockade of activation of NF-kappa B might be a potential access to the improvement in myocardial function with the use of TFH for treatment of hypertension and chronic cardiac insufficiency.
A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome (2001)

LP299V seems to have a beneficial effect in patients with IBS. Further studies on larger cohorts of patients and with longer duration of therapy are required in order to establish the place of L. plantarum in the treatment of IBS.
Exploring the selectivity of PI3Kα and mTOR inhibitors by 3D-QSAR, molecular dynamics simulations and MM/GBSA binding free energy decomposition (2013)

PI3Kα (phosphatidylinositol-3-kinase α) and mTOR (the mammalian target of rapamycin) have been treated as anticancer targets in recent years. Since isoform-specific inhibitors may be tolerated at doses that result in complete inhibition without generating side effects, a selectivity study is valuable. In this paper, 3D-QSAR CoMFA models on 72 selective inhibitors were established using the conformations docked to the homology models, which show satisfactory linear correlations (PI3Kα: r2 = 0.839, rpred2 = 0.743; mTOR: r2 = 0.813, rpred2 = 0.932). The results reveal that the electrostatic field in the hinge region, the steric field and electrostatic field in the solvent accessible region and the affinity subpocket have critical impacts on selectivity. To validate the 3D-QSAR models and further explore the origin of the selectivity at the amino acid residue level, molecular dynamics simulations followed by MM/GBSA binding free energy decomposition were conducted, and the result shows that R770, S773, Q859 of PI3Kα and E2190, C2243 of mTOR are the significant residues, which is in accordance with the 3D-contour maps of CoMFA. By combination of comparative analysis of binding sites, building of 3D-QSAR models and MM/GBSA binding free energy decomposition, those residues which can introduce ligand selectivity were discovered and further validated.
Cyclophilin Inhibitors as a Novel HCV Therapy (2010)

A critical role of Cyclophilins, mostly Cyclophilin A (CyPA), in the replication of HCV is supported by a growing body of in vitro and in vivo evidence. CyPA probably interacts directly with nonstructural protein 5A to exert its effect, through its peptidyl-prolyl isomerase activity, on maintaining the proper structure and function of the HCV replicase. The major proline substrates are located in domain II of NS5A, centered around a "DY" dipeptide motif that regulates CyPA dependence and CsA resistance. Importantly, Cyclosporine A derivatives that lack immunosuppressive function efficiently block the CyPA-NS5A interaction and inhibit HCV in cell culture, an animal model, and human trials. Given the high genetic barrier to development of resistance and the distinctness of their mechanism from that of either the current standard of care or any specifically targeted antiviral therapy for HCV (STAT-C), CyP inhibitors hold promise as a novel class of anti-HCV therapy.
An automatic image registration for applications in remote sensing (2005)

This paper deals with a major problem encountered in the area of remote sensing consisting of the registration of multitemporal and/or multisensor images. In general, such images have different gray-level characteristics, and simple techniques such as those based on correlation cannot be applied directly. In this work, a new automatic satellite image registration approach is proposed. This technique exploits the invariant relations between regions of a reference and a sensed image, respectively. It involves an edge-based selection of the most distinctive control points (CPs) in the reference image. The search for the corresponding CPs in the sensed image is based on local similarity detection by means of template matching according to a combined invariants-based similarity measure. The final warping of the images according to the selected CPs is performed by using the thin-plate spline interpolation. The procedure is fully automatic and computationally efficient. The proposed algorithm for this technique has been successfully applied to register multitemporal SPOT and synthetic aperture radar images from urban and agricultural areas. The experimental results demonstrate the robustness, efficiency and accuracy of the algorithm.
Escape of HIV-1-Infected Dendritic Cells from TRAIL-Mediated NK Cell Cytotoxicity during NK-DC Cross-Talk—A Pivotal Role of HMGB1 (2010)

Early stages of Human Immunodeficiency Virus-1 (HIV-1) infection are associated with local recruitment and activation of important effectors of innate immunity, i.e. natural killer (NK) cells and dendritic cells (DCs). Immature DCs (iDCs) capture HIV-1 through specific receptors and can disseminate the infection to lymphoid tissues following their migration, which is associated to a maturation process. This process is dependent on NK cells, whose role is to keep in check the quality and the quantity of DCs undergoing maturation. If DC maturation is inappropriate, NK cells will kill them ("editing process") at sites of tissue inflammation, thus optimizing the adaptive immunity. In the context of a viral infection, NK-dependent killing of infected-DCs is a crucial event required for early elimination of infected target cells. Here, we report that NK-mediated editing of iDCs is impaired if DCs are infected with HIV-1. We first addressed the question of the mechanisms involved in iDC editing, and we show that cognate NK-iDC interaction triggers apoptosis via the TNF-related apoptosis-inducing ligand (TRAIL)-Death Receptor 4 (DR4) pathway and not via the perforin pathway. Nevertheless, once infected with HIV-1, DC(HIV) become resistant to NK-induced TRAIL-mediated apoptosis. This resistance occurs despite normal amounts of TRAIL released by NK cells and comparable DR4 expression on DC(HIV). The escape of DC(HIV) from NK killing is due to the upregulation of two anti-apoptotic molecules, the cellular-Flice like inhibitory protein (c-FLIP) and the cellular inhibitor of apoptosis 2 (c-IAP2), induced by NK-DC(HIV) cognate interaction. High-mobility group box 1 (HMGB1), an alarmin and a key mediator of NK-DC cross-talk, was found to play a pivotal role in NK-dependent upregulation of c-FLIP and c-IAP2 in DC(HIV). Finally, we demonstrate that restoration of DC(HIV) susceptibility to NK-induced TRAIL killing can be obtained either by silencing c-FLIP and c-IAP2 by specific siRNA, or by inhibiting HMGB1 with blocking antibodies or glycyrrhizin, arguing for a key role of HMGB1 in TRAIL resistance and DC(HIV) survival. These findings provide evidence for a new strategy developed by HIV to escape immune attack, they challenge the question of the involvement of HMGB1 in the establishment of viral reservoirs in DCs, and they identify potential therapeutic targets to eliminate infected DCs.
Electrocatalytic Recycling of CO2 and Small Organic Molecules (2009)

As global warming directly affects the ecosystems and humankind in the 21st century, attention and efforts are continuously being made to reduce the emission of greenhouse gases, especially carbon dioxide (CO2). In addition, there have been numerous efforts to electrochemically convert CO2 gas to small organic molecules (SOMs) and vice versa. Herein, we highlight recent advances made in the electrocatalytic recycling of CO2 and SOMs including (i) the overall trend of research activities made in this area, (ii) the relations between reduction conditions and products in the aqueous phase, (iii) the challenges in the use of gas diffusion electrodes for the continuous gas phase CO2 reduction, as well as (iv) the development of state of the art hybrid techniques for industrial applications. Perspectives geared to fully exploit the potential of zero-gap cells for CO2 reduction in the gaseous phase and the high applicability on a large scale are also presented. We envision that the hybrid system for CO2 reduction supported by sustainable solar, wind, and geothermal energies and waste heat will provide a long term reduction of greenhouse gas emissions and will allow for continued use of the abundant fossil fuels by industries and/or power plants but with zero emissions.
Mössbauer Studies of the Membrane-Associated Methane Monooxygenase from Methylococcus capsulatus Bath:  Evidence for a Diiron Center (2007)

Two methane monooxygenase (MMO) systems have been identified in methanotrophic bacteria, namely, a soluble or cytoplasmic MMO and a membrane-associated or particulate MMO. The active site of the well-characterized soluble MMO contains a bis-mu-hydroxo-bridged diiron cluster. X-ray crystallographic studies of the particulate enzyme, pMMO, have identified two copper centers on the alpha subunit (pmoB) of the alphabetagamma trimer and a site at the interface of the betagamma subunits filled by a Zn, apparently from the crystallization buffer. In our hands, pMMO preparations containing 1-2 iron atoms per alphabetagamma show the highest catalytic activity. We have employed Mössbauer spectroscopy to characterize the iron in our preparations. Interestingly, we find in pMMO a component with the same spectral properties as the antiferromagnetically coupled diiron(III) cluster in the soluble enzyme. In whole cells, we find nearly 1 diiron center per alphabetagamma of pMMO; in purified enzyme preparations, only 10% of the sites appear to be occupied. These occupancies correlate well with the measured specific activities of purified pMMO and pMMO in whole cells. We suggest that it is the "Zn site" that accommodates the diiron center in active pMMO.
Transparent elastic capacitive pressure sensors based on silver nanowire electrodes (2013)

Stretchable conductive films were produced by embedding silver nanowires onto the surface of biocompatible polydimethylsiloxane (PDMS) elastomeric membranes with low cost solution based processes. The films showed low sheet resistance (<;12Ω/□) and good transparency (40% at 550nm). By laminating two films together, transparent elastic capacitive pressure sensors were made, which present higher sensitivity to that using Al foil as the electrode. A higher concentration of silver nanowire solution was also shown to be able to improve the sensitivity.
Concurrent enhancement of transcriptional activity and specificity of a retinal pigment epithelial cell-preferential promoter. (2004)

Our results indicate that the current transgene expression system dramatically amplifies transcriptional activity of weak and cell-specific/preferential promoters (e.g., the hRPE65 promoter) whilst retaining relative cell specificity.
Identification of a domain in Rck, a product of the Salmonella typhimurium virulence plasmid, required for both serum resistance and cell invasion (1996)

Rck is encoded on the Salmonella typhimurium virulence plasmid and is a member of a family of related 17- to 19-kDa outer membrane proteins of Enterobacteriaceae, including Ail (Yersinia enterocolitica) and PagC (S. typhimurium). Structural models for these proteins predict eight membrane-spanning domains alternating with hydrophilic inner and outer loops. When expressed in Escherichia coli, Rck and Ail, but not PagC, confer high-level resistance to the bactericidal activity of complement as well as the ability to adhere to and invade mammalian cell lines. To identify functional domains of Rck, we made and screened random mutations in Rck for decreased bioactivity. We found that a single amino acid substitution (glycine to aspartic acid) in the putative third outer loop greatly reduced Rck-mediated serum resistance and eukaryotic cell invasion. We then constructed two chimeric proteins between Rck and PagC. Substitution of the C-terminal half of Rck with the corresponding PagC fragment containing both the third and the fourth outer loops abolishes the Rck-mediated serum resistance and invasion phenotypes. Substitution of Rck with a smaller C-terminal portion of PagC containing the fourth outer loop did not affect the invasive phenotype or serum resistance. These data reveal that the third putative outer membrane loop region is important for the virulence-associated properties of the Rck protein and suggest a similarity between the mechanism of serum resistance and epithelial cell invasion involving the same domain of Rck.
Effects of Growth Mode and Pyruvate Carboxylase on Succinic Acid Production by Metabolically Engineered Strains of Escherichia coli (2002)

Escherichia coli NZN111, which lacks activities for pyruvate-formate lyase and lactate dehydrogenase, and AFP111, a derivative which contains an additional mutation in ptsG (a gene encoding an enzyme of the glucose phophotransferase system), accumulate significant levels of succinic acid (succinate) under anaerobic conditions. Plasmid pTrc99A-pyc, which expresses the Rhizobium etli pyruvate carboxylase enzyme, was introduced into both strains. We compared growth, substrate consumption, product formation, and activities of seven key enzymes (acetate kinase, fumarate reductase, glucokinase, isocitrate dehydrogenase, isocitrate lyase, phosphoenolpyruvate carboxylase, and pyruvate carboxylase) from glucose for NZN111, NZN111/pTrc99A-pyc, AFP111, and AFP111/pTrc99A-pyc under both exclusively anaerobic and dual-phase conditions (an aerobic growth phase followed by an anaerobic production phase). The highest succinate mass yield was attained with AFP111/pTrc99A-pyc under dual-phase conditions with low pyruvate carboxylase activity. Dual-phase conditions led to significant isocitrate lyase activity in both NZN111 and AFP111, while under exclusively anaerobic conditions, an absence of isocitrate lyase activity resulted in significant pyruvate accumulation. Enzyme assays indicated that under dual-phase conditions, carbon flows not only through the reductive arm of the tricarboxylic acid cycle for succinate generation but also through the glyoxylate shunt and thus provides the cells with metabolic flexibility in the formation of succinate. Significant glucokinase activity in AFP111 compared to NZN111 similarly permits increased metabolic flexibility of AFP111. The differences between the strains and the benefit of pyruvate carboxylase under both exclusively anaerobic and dual-phase conditions are discussed in light of the cellular constraint for a redox balance.
Exploration of a liver-specific, glucose/insulin-responsive promoter in transgenic mice (1993)

The functional role of the different sites binding transcriptional factors on the tissue-specific, glucose-responsive promoter of the L type pyruvate kinase gene (L-PK) has been investigated in transgenic mice. These sites are able to bind, from 3' to 5', HNF1, NF1, HNF4, and MLTF/USF, respectively. We have compared the level of chloramphenicol acetyltransferase reporter transgene expression when driven by a L-PK promoter fragment of either -96 base pairs (bp) (containing only the HNF1 binding site) or -150 bp (lacking the MLTF/USF binding site) or driven by a -183-bp L-PK promoter fragment with or without the NF1 binding site. Our results demonstrate that: 1) HNF1 alone is not sufficient to promote an efficient L-PK gene transcription in vivo; 2) with only binding sites for HNF1, NF1, and HNF4, though the tissue-specific pattern of expression is respected, the level of the gene transcription is low and the hormonal control is lost; 3) the MLTF/USF binding site is the target of the hormonal control, required for both positive response to carbohydrates and negative response to glucagon; 4) the role of NF1 in the promoter activity could be to negatively modulate the L-PK gene expression in the different tissues, without interfering with the glucose and hormone responsiveness.
Traffic sign recognition in color image sequences (2003)

At the Daimler-Benz Research Center in Ulm a system for traffic sign recognition is under development. The task of the system is to detect and interpret traffic signs in colour image sequences; these images are acquired by a camera mounted in a car. The color segmentation of the incoming images is performed with a high order neural network. Based on this color segmented images and using a priori knowledge, hypotheses on image regions containing traffic signs are generated. The kind of traffic sign is also hypothesized. The preselected image regions are further analysed in order to verify or reject the hypothesis. The analysis finally interprets the contents of the traffic signs. The control of the analysis is supported by knowledge on traffic signs and outdoor scenes in general. The whole knowledge is stored in a framebased network.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Riboswitch-dependent gene regulation and its evolution in the plant kingdom (2007)

Riboswitches are natural RNA sensors that affect gene control via their capacity to bind small molecules. Their prevalence in higher eukaryotes is unclear. We discovered a post-transcriptional mechanism in plants that uses a riboswitch to control a metabolic feedback loop through differential processing of the precursor RNA 3' terminus. When cellular thiamin pyrophosphate (TPP) levels rise, metabolite sensing by the riboswitch located in TPP biosynthesis genes directs formation of an unstable splicing product, and consequently TPP levels drop. When transformed in plants, engineered TPP riboswitches can act autonomously to modulate gene expression. In an evolutionary perspective, a TPP riboswitch is also present in ancient plant taxa, suggesting that this mechanism is active since vascular plants emerged 400 million years ago.
A codon deletion confers resistance to herbicides inhibiting protoporphyrinogen oxidase (2006)

Herbicides that act by inhibiting protoporphyrinogen oxidase (PPO) are widely used to control weeds in a variety of crops. The first weed to evolve resistance to PPO-inhibiting herbicides was Amaranthus tuberculatus, a problematic weed in the midwestern United States that previously had evolved multiple resistances to herbicides inhibiting two other target sites. Evaluation of a PPO-inhibitor-resistant A. tuberculatus biotype revealed that resistance was a (incompletely) dominant trait conferred by a single, nuclear gene. Three genes predicted to encode PPO were identified in A. tuberculatus. One gene from the resistant biotype, designated PPX2L, contained a codon deletion that was shown to confer resistance by complementation of a hemG mutant strain of Escherichia coli grown in the presence and absence of the PPO inhibitor lactofen. PPX2L is predicted to encode both plastid- and mitochondria-targeted PPO isoforms, allowing a mutation in a single gene to confer resistance to two herbicide target sites. Unique aspects of the resistance mechanism include an amino acid deletion, rather than a substitution, and the dual-targeting nature of the gene, which may explain why resistance to PPO inhibitors has been rare.
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases (2014)

Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session.