gebhart/patrepeval huggingface dataset:
Production and Biologic Interactions of Prostacyclin and Platelet-Activating Factor in Acute Myocardial Ischemia in the Perfused Rabbit Heart (1990)

This study showed that the 1-O-hexadecyl form of platelet-activating factor (PAF) is released along with 6-keto-prostacyclin1 alpha (6-keto-PGF1 alpha) in the perfusates of ischemic-isolated rabbit heart. During the early phase of the reperfusion, the release of PAF and 6-keto-PGF1 alpha was particularly increased (PAF, from 5.4 +/- 1.2 to 19.7 +/- 2.0 ng/min; 6-keto-PGF1 alpha, from 2.3 +/- 0.1 to 27.4 +/- 1.8 ng/min) and this event was coupled with the characteristic mechanical alterations of myocardial performance and perfusion pressure (PP). These changes were effectively antagonized by pretreatment of the hearts with both prostacyclin (PGI2, 20 ng/ml) and the PGI2-releaser defibrotide (400 micrograms/ml). The protecting activity observed with PGI2 was paralleled by a reduction in the rate of PAF release during reperfusion (from 19.7 +/- 2.0 to 6.8 +/- 0.2 ng/min). In defibrotide-treated preparations, inhibition of PAF formation was associated with a pronounced stimulation of 6-keto-PGF1 alpha generation, which was particularly marked on reperfusion (from 27.4 +/- 1.8 to 197.5 +/- 8.2 ng/min). Indomethacin (1 microgram/ml) ablated the antiischemic effect of defibrotide but did not potentiate the rate of formation of PAF despite inhibition of 6-keto-PGF1 alpha biosynthesis. From these results, we conclude that in a model of severe myocardial ischemia, in which the major determinants of cardiac performance are under control, generation of PAF and PGI2 appears to play an important biologic role in determination of the severity of myocardial ischemic damage.
Automated screening method for determining optimum preservative systems for personal and home care products. (1998)

A procedure was designed to determine the minimum preservative level (MPL) for personal and home care products. A highly preserved sample and an unpreserved sample were combined at different concentrations within a 96-well microtiter plate by using an autodilutor. A unique tip design made it possible to accurately deliver viscous test materials that cannot be dispensed using vacuum- or fluid-filled systems. After inoculation, the sample was evaluated at a specified time interval for the presence of surviving bacteria, yeast, and mold. The lowest concentration of preservative with no microbial growth is the recommended level of preservative for the product. Because sample turbidity may interfere with determination of the endpoint, a colorimetric endpoint was used to indicate growth of microorganisms and to differentiate product from growth. The predicted levels were tested with a modified Cosmetic, Toiletry, and Fragrance Association method. The method successfully predicted effective preservative levels in many personal and home care products with a broad range of viscosities.
A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern. (1996)

Adrenoleukodystrophy (ALD), a severe demyelinating disease, is caused by mutations in a gene coding for a peroxisomal membrane protein (ALDP), which belongs to the superfamily of ATP binding cassette (ABC) transporters and has the structure of a half transporter. ALDP showed 38% sequence identity with another peroxisomal membrane protein, PMP70, up to now its closest homologue. We describe here the cloning and characterization of a mouse ALD-related gene (ALDR), which codes for a protein with 66% identity with ALDP and shares the same half transporter structure. The ALDR protein was overexpressed in COS cells and was found to be associated with the peroxisomes. The ALD and ALDR genes show overlapping but clearly distinct expression patterns in mouse and may thus play similar but nonequivalent roles. The ALDR gene, which appears highly conserved in man, is a candidate for being a modifier gene that could account for some of the extreme phenotypic variability of ALD. The ALDR gene is also a candidate for being implicated in one of the complementation groups of Zellweger syndrome, a genetically heterogeneous disorder of peroxisome biogenesis, rare cases of which were found to be associated with mutations in the PMP70 (PXMP1) gene.
Antibody synthesis by bone marrow cells in vitro following primary and booster tetanus toxoid immunization in humans. (1984)

Normal volunteers received either initial or booster immunization with tetanus toxoid. Bone marrow and peripheral blood mononuclear cells were obtained for up to 28 d after immunization and were analyzed for synthesis of total Ig and specific antibodies to tetanus toxoid. Cells were cultured in vitro for 3 or 7 d with or without pokeweed mitogen (PWM). Synthesis of IgG and IgM antibodies to tetanus (IgG-Tet and IgM-Tet) and total IgG and IgM was determined by radioimmunoassay. Four functional B cell subpopulations were detected in the bone marrow after booster tetanus immunization: (a) B cells that spontaneously synthesized IgG-Tet appeared on day 7 after immunization but were undetectable by day 21; (b) B cells that synthesized IgG-Tet after stimulation with PWM appeared after day 21 and persisted for greater than 1 mo; (c) B cells that synthesized IgM-Tet in the presence of PWM were detectable before and after immunization; and (d) B cells that spontaneously synthesized IgM-Tet appeared on day 7 and were undetectable by day 21. In contrast to the other three types of bone marrow B cells described, this fourth subpopulation of PWM-independent IgM-Tet-synthesizing B cells was not detected in the peripheral blood. After primary immunization, no spontaneous antibody-producing cells were detected in the blood or bone marrow, although there was a small rise in IgM-Tet in two of three subjects. In the bone marrow, only IgM-Tet PWM-inducible cells were seen, although mitogen-responsive IgM and IgG-Tet cells were detected in the circulation. The IgM-Tet PWM-reactive cells were present even before primary antigen exposure and appear to represent the initial B cells involved in the antibody response. These data indicate that there are specific times after immunization when different functional classes of anti-Tet-synthesizing B cells and memory B cells appear in human bone marrow. Knowledge of these data may be important in developing a strategy for the transfer of immune memory from donors to recipients in the setting of bone marrow transplantation.
Cloning and expression in Escherichia coli of pectinase genes of Erwinia carotovora subsp. carotovora (1985)

Genes coding for an endo-pectate lyase, an exo-pectate lyase, and an endopolygalacturonase of Erwinia carotovora subsp. carotovora Ecc71 were cloned in Escherichia coli HB101, using the cosmid pHC79. The products of the cloned pectinase genes paralleled their counterparts in strain Ecc71 in isoelectric mobility, mode of substrate degradation, and ability to macerate potato tuber tissue.
Functional analysis of the T-cell-restricted protein tyrosine kinase Txk (1998)

T lymphocytes express a range of tyrosine kinases that are involved in signalling processes driving cell activation, proliferation and differentation. Two tyrosine kinases expressed only in T cells, the Itk/Emt and Txk gene products, are members of the Tec family of kinases. The role of Tec kinases in cellular function is poorly understood, although a Tec kinase specific to B cells, Btk, is essential for B-cell development. To explore the contribution of the T-cell-specific Tec kinases to lymphocyte function, we have expressed human Txk in the baculovirus system and conducted the first characterization of its activity. We find that Txk exhibits a substrate preference in vitro quite distinct from that of the major T-cell kinases Lck and ZAP70, suggesting that Tec-family kinases might act on a distinct range of substrates. We also investigated the interactions of Txk with the cytoplasmic domains of the key signalling molecules CD3zeta, CD28 and CTLA4 and find that none of these are phosphorylated by Txk, nor are they ligands for the SH2 or SH3 domains of Txk. We conclude that it is unlikely that Txk has a role in the early signal transduction events associated with these key pathways controlling T-cell activation.
Discovery of the Novel Antithrombotic Agent 5-Chloro-N-({(5S)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene- 2-carboxamide (BAY 59-7939):  An Oral, Direct Factor Xa Inhibitor (2005)

Despite recent progress in antithrombotic therapy, there is still an unmet medical need for safe and orally available anticoagulants. The coagulation enzyme Factor Xa (FXa) is a particularly promising target, and recent efforts in this field have focused on the identification of small-molecule inhibitors with good oral bioavailability. We identified oxazolidinone derivatives as a new class of potent FXa inhibitors. Lead optimization led to the discovery of BAY 59-7939 (5), a highly potent and selective, direct FXa inhibitor with excellent in vivo antithrombotic activity. The X-ray crystal structure of 5 in complex with human FXa clarified the binding mode and the stringent requirements for high affinity. The interaction of the neutral ligand chlorothiophene in the S1 subsite allows for the combination of good oral bioavailability and high potency for nonbasic 5. Compound 5 is currently under clinical development for the prevention and treatment of thromboembolic diseases.
Localization of T cells, macrophages and dendritic cells in rat respiratory tract tissue: implications for immune function studies. (1987)

Monoclonal antibodies against a range of surface markers were used to localize T cells, macrophages and dendritic cells (DC) in sections of rat trachea and peripheral lung, employing the immunoperoxidase technique. A population of Ia-bearing cells with characteristic DC morphology was identified within the tracheal epithelium, closely associated with the basement membrane, and Ia+ dendritic processes from these cells penetrated the epithelium reaching the overlying fluid layer. A second DC-like population, also Ia+ but differing from the airway DC in expression of other markers, was identified within the alveolar septal walls. Both types of DC were intimately associated with populations of pleiomorphic heterogenously staining macrophages. In addition, a large population of T lymphocytes was identified within the alveolar septa; the lymphocytes occurred as single, isolated cells, distributed randomly throughout the lung parenchyma.
Use of Vis-SWIR imagery to aid atmospheric correction of multispectral and hyperspectral thermal infrared TIR imagery: The TIR model (2002)

The atmospheric correction of thermal infrared (TIR) imagery involves the combined tasks of separation of atmospheric transmittance, downwelling flux and upwelling radiance from the surface material spectral emissivity and temperature. The problem is ill posed and is thus hampered by spectral ambiguity among several possible feasible combinations of atmospheric temperature, constituent profiles, and surface material emissivities and temperatures. For many materials, their reflectance spectra in the Vis-SWIR provide a means of identification or at least classification into generic material types, vegetation, soil, etc. If Vis-SWIR data can be registered to TIR data or collected simultaneously as in sensors like the MASTER sensor, then the additional information on material type can be utilized to help lower the ambiguities in the TIR data. If the Vis-SWIR and TIR are collected simultaneously the water column amounts obtained form the atmospheric correction of the Vis-SWIR can also be utilized in reducing the ambiguity in the atmospheric quantities. The TIR atmospheric correction involves expansions in atmospheric and material emissivity basis sets. The method can be applied to hyperspectral and ultraspectral data, however it is particularly useful for multispectral TIR, where spectral smoothness techniques cannot be readily applied. The algorithm is described, and the approach applied to a MASTER sensor data set.
Lymphocyte infiltration in the injured brain: Role of proinflammatory cytokines (2003)

Studies using mouse axotomised facial motoneuron model show a strong and highly selective entry of CD3+ lymphocytes into the affected nucleus, with a maximum at Day 14, which coincides with the peak of neuronal cell death, microglial phagocytosis, and increased synthesis of interleukin-1 beta (IL1beta), tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma). We explored the possible involvement of these cytokines during the main phase of lymphocyte recruitment into the axotomised facial motor nucleus 7-21 days after nerve cut using mice homozygously deficient for IL1 receptor type 1 (IL1R1-/-), TNF receptor type 1 (TNFR1-/-), type 2 (TNFR2-/-) and type 1 and 2 (TNFR1&2-/-), IFNgamma receptor type 1 (IFNgammaR1-/-), and the appropriate controls for the genetic background. Transgenic deletion of IL1R1 led to a 54% decrease and that of TNFR2 to a 44% reduction in the number of CD3+ T-cells in the axotomised facial motor nucleus, with a similar relative decrease at Day 7, 14, and 21. Deletion of TNFR1 or IFNgammaR1 had no significant effect. Deletion of both TNFR1 and 2 (TNFR1&2-/-) caused a somewhat stronger, 63% decrease than did TNFR2 deletion alone, but this could be due to an almost complete inhibition of neuronal cell death. No mutations seemed to inhibit aggregation of CD3+ T-cells around glial nodules consisting of Ca-ion binding adaptor protein-1 (IBA1)+ phagocytotic microglia and neuronal debris. Altogether, the current data show the importance of IL1R1 and TNFR2 as the key players during the main phase of lymphocyte recruitment to the damaged part of the central nervous system.
Widespread Head-to-Head Hydrocarbon Biosynthesis in Bacteria and Role of OleA (2010)

Previous studies identified the oleABCD genes involved in head-to-head olefinic hydrocarbon biosynthesis. The present study more fully defined the OleABCD protein families within the thiolase, alpha/beta-hydrolase, AMP-dependent ligase/synthase, and short-chain dehydrogenase superfamilies, respectively. Only 0.1 to 1% of each superfamily represents likely Ole proteins. Sequence analysis based on structural alignments and gene context was used to identify highly likely ole genes. Selected microorganisms from the phyla Verucomicrobia, Planctomyces, Chloroflexi, Proteobacteria, and Actinobacteria were tested experimentally and shown to produce long-chain olefinic hydrocarbons. However, different species from the same genera sometimes lack the ole genes and fail to produce olefinic hydrocarbons. Overall, only 1.9% of 3,558 genomes analyzed showed clear evidence for containing ole genes. The type of olefins produced by different bacteria differed greatly with respect to the number of carbon-carbon double bonds. The greatest number of organisms surveyed biosynthesized a single long-chain olefin, 3,6,9,12,15,19,22,25,28-hentriacontanonaene, that contains nine double bonds. Xanthomonas campestris produced the greatest number of distinct olefin products, 15 compounds ranging in length from C(28) to C(31) and containing one to three double bonds. The type of long-chain product formed was shown to be dependent on the oleA gene in experiments with Shewanella oneidensis MR-1 ole gene deletion mutants containing native or heterologous oleA genes expressed in trans. A strain deleted in oleABCD and containing oleA in trans produced only ketones. Based on these observations, it was proposed that OleA catalyzes a nondecarboxylative thiolytic condensation of fatty acyl chains to generate a beta-ketoacyl intermediate that can decarboxylate spontaneously to generate ketones.
A Return to Our Roots: Some Observations (2003)

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The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain (2013)

The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB₂). It is found in relatively high concentrations in many spices and food plants. A number of studies have shown that CB₂ is critically involved in the modulation of inflammatory and neuropathic pain responses. In this study, we have investigated the analgesic effects of BCP in animal models of inflammatory and neuropathic pain. We demonstrate that orally administered BCP reduced inflammatory (late phase) pain responses in the formalin test in a CB₂ receptor-dependent manner, while it had no effect on acute (early phase) responses. In a neuropathic pain model the chronic oral administration of BCP attenuated thermal hyperalgesia and mechanical allodynia, and reduced spinal neuroinflammation. Importantly, we found no signs of tolerance to the anti-hyperalgesic effects of BCP after prolonged treatment. Oral BCP was more effective than the subcutaneously injected synthetic CB₂ agonist JWH-133. Thus, the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.
Acid β-Glucosidase:  Intrinsic Fluorescence and Conformational Changes Induced by Phospholipids and Saposin C (1998)

Acid beta-glucosidase is a lysosomal membrane protein that cleaves the O-beta-D-glucosidic linkage of glucosylceramide and aryl-beta-glucosides. Full activity reconstitution of the pure enzyme requires phospholipids and saposin C, an 80 aa activator protein. The deficiency of the enzyme or activator leads to Gaucher disease. A conformational change of acid beta-glucosidase is shown to accompany activity reconstitution by selected phospholipids or, particularly, phospholipid/saposin C complexes by intrinsic fluorescence spectral shifts, fluorescence quenching, and circular dichroism (CD). Negatively charged phospholipid (NCP) interfaces with unsaturated fatty acid acyl chains (UFAC) induced concordant blue-shifts in tryptophanyl fluorescence spectra and a loss of beta-strand structure by CD. The enzyme required an unsaturated fatty acid acyl chain in proximity (10-11 A) within liposomal membranes for activation, fluorescence blue-shifts, and changes in CD spectra. Activity enhancements were greatest when UFAC and the negatively charged headgroup were present on the same phospholipid. NCPs with UFAC protected the enzyme from fluorescence quenching by aqueous agents (I-, Cs+, acrylamide, TEMPO). Phosphatidylcholine with doxyl spin-labeled fatty acid acyl chains at carbons 7, 10, or 16 quenched enzyme fluorescence only when in NCP/PC liposomes. Saposin C (Trp-free) induced additional activity and fluorescence spectral changes in the enzyme only in the presence of NCP liposomes containing UFA. CD spectral changes indicated saposin C and acid beta-glucosidase interaction only in the presence of NCPs with UFA. These studies show that acid beta-glucosidase requires interfaces composed of NCPs, containing UFAC, for penetration into the outer leaflet of membranes. Furthermore, this interaction induces essential conformational changes for saposin C binding and further enhancement of acid beta-glucosidase catalytic activity.
Sialyloligosaccharides in Human and Bovine Milk and in Infant Formulas: Variations with the Progression of Lactation (2003)

Several lines of research support a role for human milk oligosaccharides in the defense of breast-fed infants against pathogens. Some ofthese oligosaccharides contain at least one moiety of sialic acid and are, thus, termed sialyloligosaccharides. These constitute a significant component (>1 g/L) of human milk. It is well established that milk composition varies among species, and previous reports have indicated that one ofthe differences between human and bovine milk is precisely their contents of sialyloligosaccharides. Because most infant formulas are manufactured with bovine milk components, it follows that formula-fed and breast-fed infants ingest dissimilar quantities of these carbohydrate structures. To ascertain these differences and their impact along lactation, the contents of oligosaccharide-bound sialic acids and major sialyloligosaccharides in samples of human and bovine milk (obtained at different lactation stages) were determined. In addition, infant formulas were assayed for their sialyloligosaccharide contents. Seven sialyloligosaccharides were identified in human milk; namely, 3'-sialyl-3-fucosyllactose and sialyllacto-N-tetraoses (a and b+c), the predominant structures at all lactation stages. Five sialyloligosaccharides were identified in bovine milk, of which 6'-sialyllactosamine and 3'-sialyllactose were the most abundant. In addition, sialyloligosaccharides in human and bovine milk decreased along lactation, and infant formulas did not contain significant amounts of sialyloligosaccharides. The results point to the general conclusion that regarding both qualitative and quantitative aspects, milk from humans and cows and infant formulas have different oligosaccharide contents. In this sense, bottle-fed infants are subject to reduced sialyloligosaccharide intake as compared to breast-fed infants.
Molecular Characterization of the Hemagglutinin Gene and Oral Immunization with a Waterfowl-Origin Avian Influenza Virus (1998)

Vaccination against highly pathogenic (HP) subtypes of avian influenza (AI) virus in poultry has been prohibited in the United States. Recently, policy has been changed to potentially allow use of inactivated vaccines in emergency programs to control HP H5 and H7 AI. Vaccination with inactivated virus against non-highly pathogenic AI viruses has been allowed in the U.S. turkey industry since 1979 (1) but requires expensive handling of individual birds for parenteral inoculation. Oral immunization would provide a less expensive method to protect commercial poultry from AI. Prime candidates for oral vaccines are waterfowl-origin (WFO) isolates, which have a tropism for the alimentary tract. One WFO isolate, A/mallard/Ohio/556/1987 (H5N9) (MOh87), was characterized by determining the complete nucleotide sequence of its hemagglutinin (HA) gene. The HA protein of this isolate possessed a deduced amino acid sequence nearly identical to the consensus amino acid sequence for all published H5 genes, indicating that it has potential as a broadly effective vaccine. Experimental results demonstrated measurable serum antibody responses to orally delivered live and inactivated preparations of MOh87. Oral vaccination also protected chickens from diverse, lethal H5 AI virus challenge strains and blocked cloacal shedding of challenge virus.