gebhart/patrepeval huggingface dataset:
Biological Investigation and Structure—Activity Relationship Studies on Azadirone from Azadirachta indica A. Juss. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
New Hypothesis on the Role of Alternating Sequences in Calcium−Alginate Gels (2005)

The availability of mannuronan and mannuronan C-5 epimerases allows the production of a strictly alternating mannuronate-guluronate (MG) polymer and the MG-enrichment of natural alginates, providing a powerful tool for the analysis of the role of such sequences in the calcium-alginate gel network. In view of the calcium binding properties of long alternating sequences revealed by circular dichroism studies which leads eventually to the formation of stable hydrogels, their direct involvement in the gel network is here suggested. In particular, 1H NMR results obtained from a mixed alginate sample containing three polymeric species, G blocks, M blocks, and MG blocks, without chemical linkages between the block structures, indicate for the first time the formation of mixed junctions between G and MG blocks. This is supported by the analysis of the Young's modulus of hydrogels from natural and epimerized samples obtained at low calcium concentrations. Furthermore, the "zipping" of long alternating sequences in secondary MG/MG junctions is suggested to account for the shrinking (syneresis) of alginate gels in view of its dependence on the length of the MG blocks. As a consequence, a partial network collapse, macroscopically revealed by a decrease in the Young's modulus, occurred as the calcium concentration in the gel was increased. The effect of such "secondary" junctions on the viscoelastic properties of alginate gels was evaluated measuring their creep compliance under uniaxial compression. The experimental curves, fitted by a model composed of a Maxwell and a Voigt element in series, revealed an increase in the frictional forces between network chains with increasing length of the alternating sequences. This suggests the presence of an ion mediated mechanism preventing the shear of the gel.
Heat Shock Protein 90 Inhibition Depletes LATS1 and LATS2, Two Regulators of the Mammalian Hippo Tumor Suppressor Pathway (2010)

Heat shock protein 90 (HSP90), which regulates the functions of multiple oncogenic signaling pathways, has emerged as a novel anticancer therapeutic target, and multiple small-molecule HSP90 inhibitors are now in clinical trials. Although the effects of HSP90 inhibitors on oncogenic signaling pathways have been extensively studied, the effects of these agents on tumor suppressor signaling pathways are currently unknown. Here, we have examined how HSP90 inhibitors affect LATS1 and the related protein LATS2, two kinases that relay antiproliferative signals in the Hippo tumor suppressor pathway. Both LATS1 and LATS2 were depleted from cells treated with the HSP90 inhibitors 17-allylamino-17-demethoxygeldanamycin (17-AAG), radicicol, and PU-H71. Moreover, these kinases interacted with HSP90, and LATS1 isolated from 17-AAG-treated cells had reduced catalytic activity, thus showing that the kinase is a bona fide HSP90 client. Importantly, LATS1 signaling was disrupted by 17-AAG in tumor cell lines in vitro and clinical ovarian cancers in vivo as shown by reduced levels of LATS1 and decreased phosphorylation of the LATS substrate YAP, an oncoprotein transcriptional coactivator that regulates genes involved in cell and tissue growth, including the CTGF gene. Consistent with the reduced YAP phosphorylation, there were increased levels of CTGF, a secreted protein that is implicated in tumor proliferation, metastasis, and angiogenesis. Taken together, these results identify LATS1 and LATS2 as novel HSP90 clients and show that HSP90 inhibitors can disrupt the LATS tumor suppressor pathway in human cancer cells.
Protein Tyrosine Phosphatase 1B Interacts With the Activated Insulin Receptor (1996)

Protein tyrosine phosphatase 1B (PTP1B) is a protein tyrosine phosphatase of unknown function, although increasing evidence supports a role for this phosphatase in insulin action. We have investigated the interaction of PTP1B with the insulin receptor using a PTP1B glutathione S-transferase (GST) fusion protein with a point mutation in the enzyme's catalytic domain. This fusion protein is catalytically inactive, but the phosphatase's phosphotyrosine binding site is maintained. The activated insulin receptor was precipitated from purified receptor preparations and whole-cell lysates by the inactive PTP1B-GST, demonstrating a direct association between the insulin receptor and PTP1B. A p120 of unknown identity was also precipitated from whole-cell lysates by the PTP1B fusion protein, but IRS-1 (pp185) was not. A catalytically inactive [35S]PTP1B-fusion protein bound directly to immobilized insulin receptor kinase domains and was displaced in a concentration-dependent manner. Finally, tyrosine-phosphorylated PTP1B was precipitated from whole-cell lysates by an anti-insulin receptor antibody after insulin stimulation. The site of interaction between PTP1B and the insulin receptor was studied using phosphopeptides modeled after the receptor's kinase domain, the NPXY domain, and the COOH-terminal. Each phosphopeptide inhibited the PTP1B-GST:insulin receptor interaction. Study of mutant insulin receptors demonstrated that activation of the kinase domain is necessary for the PTP1B:insulin receptor interaction, but receptors with deletion of the NPXY domain or of the COOH-terminal can still bind to the PTP1B-GST. We conclude that PTP1B can associate directly with the activated insulin receptor at multiple different phosphotyrosine sites and that dephosphorylation by PTP1B may play a significant role in insulin receptor signal transduction.
The Liga Process for Fabrication of Three-Dimensional Microscale Structures (1993)

Three-dimensional microscale structures can be fabricated with the Liga process, which uses deep etch X-ray lithography, electroforming and plastic moulding. The basic process has been extended in order to increase the number of possible applications. Some of the extensions include: movable microscale structures produced using a sacrificial layer technique; structures with different shapes in the third dimension obtained by patterning plastic substrates as well as by a moulding technique and by X-ray lithography; and micropumps developed by combining Liga with a membrane technology. The improved process together with the great variety of materials (plastics, metals, alloys, ceramics) that can be used opens up many potential applications of Liga in microsystem technologies. A few prototype applications are briefly described: microturbines with diameters of the order of 100 μm, rotating at 150 000 rev min–1 for 108 revolutions; microsensors which can measure acceleration with high accuracy, e.g. of crashing cars; micromotors with diameters of 0·25 mm driven by electrical forces; and micropumps which can deliver very small amounts of liquids and even gases. In the future all these microcomponents will be integrated with microelectronic devices to create 'intelligent' microsystems which are expected to change our life in the way that the microelectronic revolution did in the past.
Quantitative evaluation of tryptophan oxidation in actin and troponin I from skeletal muscles using a rat model of acute oxidative stress (2010)

Increased levels of "ROS" cause oxidative stress and are believed to play a key role in the development of age-related diseases and mammalian aging, e.g. through the oxidation of residues, at or close to, the protein surface. In this study, we have investigated the effects of ROS on tryptophan residues in alpha skeletal actin and troponin I (fast skeletal muscle isoform) using an established rat model of acute oxidative stress induced by X-ray irradiation. In the control samples (no oxidative stress), the single Trp residue of troponin I (position 161) and the four tryptophan residues present in actin (positions 79, 86, 340, and 356) were only oxidized at very low levels. Post-irradiation, the level of oxidized versions increased for most positions within 3 h. Tryptophan residues located inside the proteins, however, required longer time periods. Based on the increment masses of the tryptophan positions calculated from the b- and y-ion series of the tandem mass spectra, the following oxidation products of tryptophan were detected: kynurenine; oxolactone; hydroxytryptophan or oxindolylalanine (isobaric); hydroxykynurenine; dioxindolylalanine, N-formylkynurenine or dihydroxytryptophan (all three isobaric); and hydroxyl-N-formylkynurenine, with mass gains relative to tryptophan of 4, 14, 16, 20, 32, and 48 u, respectively. Despite a partial recovery after 24 h, the degree of oxidation of all oxidized versions was still higher than in the control samples.
Porcine Repeat Element DNA: In Situ Detection of Xenotransplanted Cells (1995)

Using a digoxygenin-labelled DNA probe derived from the porcine repeat element PRE-1, we have developed a protocol for the detection of transplanted porcine islets and hepatocytes against a background of murine host tissue. Analysis of this probe by Southern blotting indicated that PRE-1 hybridizes to pig genomic DNA but not to human or mouse DNA. On tissue sections, hybridizing probe was detected using alkaline phosphatase-conjugated anti-digoxygenin antibody visualized with 5-bromo-4-chloro-3-indolyl-phosphate/4-nitro-blue tetrazolium chloride (BCIP/ NBT) substrate. We have demonstrated sensitive and highly specific staining of porcine nuclei in fixed, paraffin embedded tissue sections, and have applied the technique to detect porcine pancreatic islets and hepatocytes transplanted into murine kidney and spleen. Applications of this technique include detection of transplanted cells or organs across a variety of xenogeneic barriers.
Molecular cloning and characterization of the human A3 adenosine receptor. (1993)

The human A3 adenosine receptor was cloned from a striatal cDNA library using a probe derived from the homologous rat sequence. The cDNA encodes a protein of 318 amino acids and exhibits 72% and 85% overall identity with the rat and sheep A3 adenosine receptor sequences, respectively. Specific and saturable binding of the adenosine receptor agonist N6-(4-amino-3-[125I]iodobenzyl)adenosine [125I]ABA was measured on the human A3 receptor stably expressed in Chinese hamster ovary cells with a Kd = 10 nM. The potency order for adenosine receptor agonists was N-ethylcarboxamidoadenosine (NECA) > or = (R)-N6-phenyl-2-propyladenosine [(R)-PIA] > N6-cyclopentyladenosine (CPA) > (S)-N6-phenyl-2-propyladenosine [(S)-PIA]. The human receptor was blocked by xanthine antagonists, most potently by 3-(3-iodo-4-aminobenzyl)-8-(4-oxyacetate)phenyl-1-propylxanthine (I-ABOPX) with a potency order of I-ABOPX > 1,3-dipropyl-8-(4-acrylate)phenylxanthine > or = xanthine amino congener >> 1,3-dipropyl-8-cyclopentylxanthine. Adenosine, NECA, (R)- and (S)-PIA, and CPA inhibited forskolin-stimulated cAMP accumulation by 30-40% in stably transfected cells; I-ABA is a partial agonist. When measured in the presence of antagonists, the dose-response curves of NECA-induced inhibition of forskolin-stimulated cAMP accumulation were right-shifted. Antagonist potencies determined by Schild analyses correlated well with those established by competition for radioligand binding. The A3 adenosine receptor transcript is widespread and, in contrast to the A1, A2a, and A2b transcripts, the most abundant expression is found in the lung and liver. The tissue distribution of A3 mRNA is more similar to the widespread profile found in sheep than to the restricted profile found in the rat. This raises the possibility that numerous physiological effects of adenosine may be mediated by A3 adenosine receptors.
Biological hydrogen production using a membrane bioreactor (2004)

A cross-flow membrane was coupled to a chemostat to create an anaerobic membrane bioreactor (MBR) for biological hydrogen production. The reactor was fed glucose (10,000 mg/L) and inoculated with a soil inoculum heat-treated to kill non-spore-forming methanogens. Hydrogen gas was consistently produced at a concentration of 57-60% in the headspace under all conditions. When operated in chemostat mode (no flow through the membrane) at a hydraulic retention time (HRT) of 3.3 h, 90% of the glucose was removed, producing 2200 mg/L of cells and 500 mL/h of biogas. When operated in MBR mode, the solids retention time (SRT) was increased to SRT = 12 h producing a solids concentration in the reactor of 5800 mg/L. This SRT increased the overall glucose utilization (98%), the biogas production rate (640 mL/h), and the conversion efficiency of glucose-to-hydrogen from 22% (no MBR) to 25% (based on a maximum of 4 mol-H(2)/mol-glucose). When the SRT was increased from 5 h to 48 h, glucose utilization (99%) and biomass concentrations (8,800 +/- 600 mg/L) both increased. However, the biogas production decreased (310 +/- 40 mL/h) and the glucose-to-hydrogen conversion efficiency decreased from 37 +/- 4% to 18 +/- 3%. Sustained permeate flows through the membrane were in the range of 57 to 60 L/m(2) h for three different membrane pore sizes (0.3, 0.5, and 0.8 microm). Most (93.7% to 99.3%) of the membrane resistance was due to internal fouling and the reversible cake resistance, and not the membrane itself. Regular backpulsing was essential for maintaining permeate flux through the membrane. Analysis of DNA sequences using ribosomal intergenic spacer analysis indicated bacteria were most closely related to members of Clostridiaceae and Flexibacteraceae, including Clostridium acidisoli CAC237756 (97%), Linmingia china AF481148 (97%), and Cytophaga sp. MDA2507 AF238333 (99%). No PCR amplification of 16s rRNA genes was obtained when archaea-specific primers were used.
Analysis of polyphenols in white wine by CZE with amperometric detection using carbon nanotube‐modified electrodes (2011)

A method for the simultaneous detection of five polyphenols (caffeic, chlorogenic, ferulic and gallic acids and (+)-catechin) by CZE with electrochemical detection was developed. Separation of these polyphenols was performed in a 100 mM borate buffer (pH 9.2) within 15 min. Under optimized separation conditions, the performance of glassy carbon (GC) electrodes modified with multiwalled carbon nanotube layer obtained from different dispersions was examined. GC electrode modified with a dispersion of multi-walled carbon nanotubes (CNT) in polyethylenimine has proven to be the most suitable CNT-based electrode for its application as amperometric detector for the CZE separation of the studied compounds. The excellent electrochemical properties of this electrode allowed the detection of the selected polyphenols at +200 mV and improved the efficiency and the resolution of their CZE separation. Limits of detection below 3.1 μM were obtained with linear ranges covering the 10⁻⁵ to 10⁻⁴ M range. The proposed method has been successfully applied for the detection (ferulic, caffeic and gallic acids and (+)-catechin) and the quantification (gallic acid and (+)-catechin) of polyphenols in two different white wines without any preconcentration step. A remarkable signal stability was observed on the electrode performance despite the presence of potential fouling substances in wine.
Ligand-independent Dimerization Activates the Stress Response Kinases IRE1 and PERK in the Lumen of the Endoplasmic Reticulum (2000)

IRE1 and PERK are type I transmembrane serine/threonine protein kinases that are activated by unfolded proteins in the endoplasmic reticulum (ER) to signal adaptive responses. IRE1 is present in all eukaryotic cells and signals the unfolded protein response through its kinase and endoribonuclease activities. PERK signals phosphorylation of a translation initiation factor to inhibit protein synthesis in higher eukaryotic cells but is absent in the Saccharomyces cerevisiae genome. The amino acid sequences of the amino-terminal ER luminal domains (NLDs) from IRE1 and PERK display limited homology and have diverged among species. In this study, we have demonstrated that the NLD of yeast Ire1p is required for signaling. However, the NLDs from human IRE1alpha and murine IRE1beta and the Caenorhabditis elegans IRE1 and PERK function as replacements for the S. cerevisiae Ire1p-NLD to signal the unfolded protein response. Replacement of the Ire1p-NLD with a functional leucine zipper dimerization motif yielded a constitutively active kinase that surprisingly was further activated by ER stress. These results demonstrate that ER stress-induced dimerization of the NLD is sufficient for IRE1 and PERK activation and is conserved through evolution. We propose that ligand-independent activation of IRE1 and PERK permits homodimerization upon accumulation of unfolded proteins in the lumen of the ER.
Urinary Tract Infections and Circumcision (1989)

It has been shown that uncircumcised infants have a higher rate of urinary tract infections in the first few months of life. To investigate further the association between noncircumcision and urinary tract infections, a case-control study was performed of infant boys who had a catheterized or suprapubic urine culture done as part of an acute illness visit. Cases (n = 36) were those infants who had a positive culture (greater than 105 organisms per milliliter); controls (n = 76) had a negative culture (less than 103 organisms per milliliter). There were no significant differences found in the two groups in age, ethnic group, and type of medical insurance. All of the cases were uncircumcised, vs 32% of controls. The data were analyzed separately by age, ethnic group, type of insurance, and method of culture, and in all groups the cases were significantly more likely to be uncircumcised. Of the 31 cases who underwent roentgenographic investigations, 8 had abnormal findings. Noncircumcision seems to be a highly significant risk factor for urinary tract infection in infants up to 12 months of age, affects infants regardless of race and socioeconomic status, and is associated with anatomic abnormalities in 26% of cases.
Coexpression with β1-subunit modifies the kinetics and fatty acid block of hH1αNa+channels (2000)

Voltage-gated cardiac Na(+) channels are composed of alpha- and beta(1)-subunits. In this study beta(1)-subunit was cotransfected with the alpha-subunit of the human cardiac Na(+) channel (hH1(alpha)) in human embryonic kidney (HEK293t) cells. The effects of this coexpression on the kinetics and fatty acid-induced suppression of Na(+) currents were assessed. Current density was significantly greater in HEK293t cells coexpressing alpha- and beta(1)-subunits (I(Na,alpha beta)) than in HEK293t cells expressing alpha-subunit alone (I(Na,alpha)). Compared with I(Na,alpha), the voltage-dependent inactivation and activation of I(Na,alpha beta) were significantly shifted in the depolarizing direction. In addition, coexpression with beta(1)-subunit prolonged the duration of recovery from inactivation. Eicosapentaenoic acid [EPA, C20:5(n-3)] significantly reduced I(Na,alpha beta) in a concentration-dependent manner and at 5 microM shifted the midpoint voltage of the steady-state inactivation by -22 +/- 1 mV. EPA also significantly accelerated channel transition from the resting state to the inactivated state and prolonged the recovery time from inactivation. Docosahexaenoic acid [C22:6(n-3)], alpha-linolenic acid [C18:3(n-3)], and conjugated linoleic acid [C18:2(n-6)] at 5 microM significantly inhibited both I(Na,alpha beta) and I(Na,alpha.) In contrast, saturated and monounsaturated fatty acids had no effects on I(Na,alpha beta). This finding differs from the results for I(Na,alpha), which was significantly inhibited by both saturated and unsaturated fatty acids. Our data demonstrate that functional association of beta(1)-subunit with hH1(alpha) modifies the kinetics and fatty acid block of the Na(+) channel.
The transcription factor XBP-1 is essential for the development and survival of dendritic cells (2007)

Dendritic cells (DCs) play a critical role in the initiation, maintenance, and resolution of an immune response. DC survival is tightly controlled by extracellular stimuli such as cytokines and Toll-like receptor (TLR) signaling, but the intracellular events that translate such extracellular stimuli into life or death for the DC remain poorly understood. The endoplasmic reticulum (ER) stress, or unfolded protein response (UPR), is a signaling pathway that is activated when unfolded proteins accumulate in the ER. The most conserved arm of the UPR involves IRE1alpha, an ER transmembrane kinase and endoribonuclease that activates the transcription factor XBP-1 to maintain ER homeostasis and prevent activation of cell death pathways caused by sustained ER stress. We report that XBP-1 is essential for DC development and survival. Lymphoid chimeras lacking XBP-1 possessed decreased numbers of both conventional and plasmacytoid DCs with reduced survival both at baseline and in response to TLR signaling. Overexpression of XBP-1 in hematopoietic progenitors rescued and enhanced DC development. Remarkably, in contrast to other cell types we have examined, the XBP-1 pathway was constitutively activated in immature DCs.
CDC25B Phosphorylation by p38 and MK-2 (2006)

CDC25B is one of the three human phosphatases that are involved in the control of the activation of cyclin-dependent kinases. CDC25B participates in regulating entry into mitosis and appears to play a key role in the checkpoint response to DNA injury. CDC25B has been reported to be regulated by a number of kinases and controversial evidence suggests that it is phosphorylated by p38SAPK and/or MAPKAP kinase-2. In this report, we clarify this issue using an approach combining mass spectrometry and the use of specific antibodies against phosphorylated CDC25B residues. We report that MAPKAP kinase-2 phosphorylates CDC25B on multiple sites including S169, S323, S353 and S375, while p38SAPK phosphorylates CDC25B on S249. We show that the S323-phosphorylated form of CDC25B is detected at the centrosome during a normal cell cycle. Since most of these sites are also phosphorylated by several other kinases, our observations highlight the difficulty in characterizing and understanding in vivo phosphorylation patterns.
Ion transport mediated by copolymers composed of polyoxyethylene and polyoxypropylene (1988)

Block copolymers composed of polyoxyethylene and polyoxypropylene were found to increase the influx of Na+ and the efflux of K+ from human erythrocytes. They were, however, ineffective at promoting the transport of Ca2+. The size of the ion fluxes induced by the copolymers correlated with their efficacy in stimulating inflammation. These compounds were also found to induce conductance increases in planar lipid bilayers in a nonvoltage dependent and nonstepwise manner. In both experimental systems, ion transport was facilitated only under temperature and ionic-strength conditions in which the polymers form aggregates in aqueous solution. In neither system did the concentration dependence of transport activity exhibit a pronounced cooperativity. These observations are consistent with the view that aqueous monomers of these surface active agents partition into the membrane, where they facilitate the conductive movement of monovalent cations by means of a carrier type mechanism. As a novel class of ionophores, these substances are of practical interest because they can be water soluble and are potentially reversible.
Serial Plasma Osteopontin Levels Have Prognostic Value in Metastatic Breast Cancer (2006)

This is the first study to show that in women with metastatic breast cancer, increases in osteopontin levels over time are strongly associated with poor survival. Sequential monitoring of osteopontin may have use in making treatment decisions for these patients.