gebhart/patrepeval huggingface dataset:
Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse embryogenesis. (1995)

Bone morphogenetic proteins (BMPs) are multifunctional proteins structurally related to transforming growth factor-beta (TGF beta) and activin that can induce cartilage and bone growth in vivo. Members of the TGF beta superfamily exert their biological effects via heteromeric serine/threonine kinase complexes of type I and type II receptors. We previously obtained six different type I receptors, termed activin receptor-like kinase-1 (ALK-1) to -6. ALK-5 is a TGF beta type I receptor, ALK-2 and ALK-4 are activin type I receptors, and ALK-3 and ALK-6 are type I receptors for osteogenic protein-1 (OP-1)/bone morphogenetic protein-7 (BMP-7) and BMP-4. Here we report the complementary DNA cloning of the mouse homolog of ALK-3, which is highly conserved between mouse and man. ALK-3 messenger RNA (mRNA) is ubiquitously expressed in various adult mouse tissues, whereas ALK-6 mRNA is only found in brain and lung. The distribution of ALK-3 and ALK-6 mRNA in the postimplantation mouse embryo [6.5-15.5 days postcoitum (pc)] was studied by in situ hybridization. ALK-3 was nearly ubiquitously expressed throughout these stages of development, but was notably absent in the liver. In contrast, ALK-6 showed a more restricted expression pattern. ALK-6 mRNA was absent in early postimplantation embryos, was detected first in 9.5 days pc embryos, and persisted until 15.5 days pc. In midgestation embryos, ALK-6 transcripts were detected in mesenchymal precartilage condensations, premuscle masses, blood vessels, central nervous system, parts of the developing ear and eye, and epithelium. The expression in sites of developing cartilage and bone supports the idea that ALK-3 and -6 are receptors for BMPs in vivo. In addition, the expression of these genes in many soft tissues suggests broader functions for BMPs in embryogenesis.
De novo production of six key grape aroma monoterpenes by a geraniol synthase-engineered S. cerevisiae wine strain (2015)

Geraniol synthase-engineered yeasts demonstrate potential in the development of monoterpene enhanced wines.
Semiquantitative measurement of cytokine messenger RNA in endomyocardium and peripheral blood mononuclear cells from human heart transplant recipients. (1996)

We conclude that changes in the expression of cytokine mRNA in both peripheral blood mononuclear cells and endomyocardial biopsy specimens as measured by the semiquantitative polymerase chain reaction method used in this study does not effectively predict rejection. The decline in peripheral blood mononuclear cell cytokine mRNA after rejection treatment is likely due to changes in the proportion of lymphocytes and monocytes in the peripheral blood in concert with a steroid-induced downregulation by cytokine gene transcription.
The Structural Roles of Amino Acid Residues Near the Carboxyl Terminus of Bovine Pancreatic Ribonuclease A (1970)

Abstract The sequence at the COOH terminus of bovine pancreatic ribonuclease A is known to be -Pro-Val-His-Phe-Asp-Ala-Ser-Val. When the last 4 residues are removed by peptic hydrolysis, the resulting des-(121-124)-RNase, which was earlier thought to be inactive, is now shown to possess about 0.5% of the activity of the native enzyme toward cyclic 2',3'-cytidylic acid. Several types of experiments show that this activity is intrinsic. The highly purified derivative binds the inhibitor 2'-cytidylic acid at pH 5.5 with a dissociation constant of 40 µm compared with 3 µm for native RNase. When the activity of the derivative is measured toward cyclic cytidylic acid, Km is 0.5 mm and the turnover number is 2 x 10-3 sec-1; these values represent a Km that is twice that of RNase but an activity that is 0.005 that of the initial enzyme. These findings are consistent with results on the alkylation of residues that are considered part of the active site of RNase; in the des-(121-124)-derivative the alkylation of histidine-12 and lysine-41 is still strongly facilitated but the susceptibility of histidine-119 is diminished. An increase in the pK of histidine-119 which could account for the alkylation results could also contribute to the diminution of the catalytic activity. The relatively strong binding of inhibitor by des-(121-124)-RNase suggests that serine-123 can have only a minor role in binding substrate. However, when phenylalanine-120 is removed from the des-(121-124)-derivative by controlled hydrolysis with carboxypeptidase A at pH 5 and 45°, the activity, the ability to bind inhibitor, and the susceptibilities of the histidine residues to alkylation are lost. The transition temperature of the des-(120-124)-derivative is lowered to 34° from 61° for RNase A. The phenylalanine residue, which in the three-dimensional structure fits into a hydrophobic pocket in the molecule, thus has an important role in maintenance of the native conformation of the enzyme. Histidine-119 as well as phenylalanine-120 can be removed by hydrolysis of the des-(121-124)-derivative by carboxypeptidase A at pH 7.6. The molecule with the 6 residues removed has a transition temperature of 32° and a structure highly susceptible to proteolysis by trypsin.
Comparative study of physical properties of water-blown rigid polyurethane foams extended with commercial soy flours (2001)

The use of renewable resources (mainly carbohydrates) in rigid polyurethane foam has been known to offer several advantages, such as increased strength, improved flame resistance, and enhanced biodegradability. Less attention has been directed to inexpensive protein-based materials, such as defatted soy flour. The objectives of this study were to develop water-blown rigid polyurethane foams, containing defatted soy flour, that have acceptable or improved physical properties which also lower the cost of the foam formulation and to compare the properties of developed foams extended with three kinds of commercial soy flour. Water-blown low-density rigid polyurethane foams were prepared with poly(ether polyol)s, polymeric isocyanates, defatted soy flour, water, a catalyst mixture, and a surfactant. Soy flour and the initial water content were varied from 0 to 40% and from 4.5 to 5.5% of the poly(ether polyol) content, respectively. A standard laboratory mixing procedure was followed for making foams using a high-speed industrial mixer. After mixing, the mixture was poured into boxes and allowed to rise at ambient conditions. Foams were removed from boxes after 1 h and cured at room temperature for 24 h before measurement of the thermal conductivity and for 1 week before other property tests. Foam properties were determined according to ASTM procedures. Measurement of the physical properties (compressive strength, modulus, thermal conductivity, and dimensional stability under thermal and humid aging) of these foams showed that the addition of 10–20% of three kinds of soy flour imparted water-blown rigid polyurethane foams with similar or improved strength, modulus, insulation, and dimensional stability. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 10–19, 2001
Defining Optimum Conditions for the Ex Vivo Expansion of Human Umbilical Cord Blood Cells. Influences of Progenitor Enrichment, Interference with Feeder Layers, Early‐Acting Cytokines and Agitation of Culture Vessels (1999)

Ex vivo expansion of human umbilical cord blood cells (HUCBC) is explored by several investigators to enhance the repopulating potential of HUCBC. We performed experiments using either Ficoll-separated or CD34+-selected HUCBC from the same donation in serum-free medium. CD34-purified HUCBC were cultured on either human umbilical vein endothelial cells (HUVEC) or irradiated bone marrow-derived stroma cells (BMSC) with addition of different cytokines. In addition, we tested the expansion of HUCBC in culture vessels with continuous rotation. CD34 enrichment led to a significant increase in the expansion factor of CD34+ cells compared with unmanipulated HUCBC. BMSC were more efficient in amplifying early progenitors than HUVEC. Optimum results were reached by a combination of SCF, FLT-3L at 300 ng/ml and IL-3 at 50 ng/ml. No significant improvement in the expansion of CD34+/38- primitive progenitors could be obtained with other combinations. Addition of megakaryocyte-derived growth and development factor to each growth factor cocktail improved the expansion results. Continuous rotation of culture vessels did not ameliorate the expansion rate of the analyzed subsets. Culture conditions separating stroma and HUCBC by a semipermeable membrane improved the expansion factors of CD34+, CD34+/38-, and CD34+/41+ cells and CFU-GM compared with contact cultures. These data might be useful when designing culture systems for clinical scale ex vivo expansion of HUCBC.
Overexpression and Purification of CytochromecOxidase fromRhodobacter sphaeroides (1998)

The aa3-type cytochrome c oxidase of Rhodobacter sphaeroides has been overexpressed up to seven fold over that in wild-type strains by engineering a multicopy plasmid with all the required oxidase genes and by establishing optimum growth conditions. The two operons containing the three structural genes and two assembly genes for cytochrome c oxidase were ligated into a pUC19 vector and reintroduced into several oxidase-deleted R. sphaeroides strains. Under conditions of relatively high pH and maximal aeration, high levels of expression were observed. A smaller expression vector, pBBR1MCS, and a fructose promoter (fruP)5 were found not to enhance cytochrome c oxidase expression in R. sphaeroides. An improved cytochrome c oxidase purification protocol is reported, which combines histidine elution from a nickel affinity column and anion-exchange chromatography, and results in a higher yield and purity than previously obtained.
Acute 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure Results in Enhanced Tyrosylphosphorylation and Expression of Murine Hepatic Cyclin Dependent Kinases (1993)

An increase in tyrosine phosphorylation of two hepatic S9 proteins migrating at 34 and 33 kDa that cross-reacted with anti-PSTAIR antibody on immunoblots was seen 24 h after administration of a single dose of 0.25, 0.5, 1 or 2 micrograms 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg to C57BL/6J female mice. Two hepatic S9 proteins migrating at 34 and 33 kDa that cross-reacted with anti-cdc2 C-terminus antibody on immunoblots were observed in corn oil control mice; increased expression of these proteins was seen with increasing doses of TCDD. A maximal increase in expression of 3-times the control was observed at 1 and 2 micrograms TCDD/kg for both p34 and p33. The stimulation of enhanced tyrosylphosphorylation and expression of cyclin dependent kinases p34cdc2 and p3cdk2 by TCDD is consistent with a mechanism of action of TCDD toxicity associated with stimulation of cellular proliferation.
Anti-phencyclidine monoclonal antibodies provide long-term reductions in brain phencyclidine concentrations during chronic phencyclidine administration in rats. (2000)

These studies examined the hypothesis that a single large dose of monoclonal anti-phencyclidine (PCP) antibody could provide long-term reductions in brain PCP concentrations despite continuous PCP administration. PCP (18 mg/kg/day, s.c.) was infused to steady-state (24 h) and then a mole-equivalent dose of a short-acting anti-PCP antigen-binding fragment (Fab) or a long-acting anti-PCP IgG was administered i.v. The PCP infusion continued for up to 27 days, even though the binding capacity of the single dose of antibody used should have been saturated within the first day. At selected time points after antibody administration, brain, testis, and serum PCP concentrations were measured. Serum PCP concentrations rapidly increased approximately 100- and 300-fold after Fab or IgG administration, respectively. Based on the antibody-bound PCP concentrations in serum, the functional elimination half-life (t(1/2lambdaZ)) values for PCP-Fab and PCP-IgG complexes were 9.4 h and 15.4 days, respectively. Fab and IgG administration produced a complete removal of PCP from the brain within 15 min. Although brain PCP concentrations were significantly decreased for only 4 h in Fab-treated animals, IgG administration resulted in significant decreases in brain PCP concentrations lasting for at least 27 days. In contrast, testis PCP concentrations were not substantially affected by antibody administration, suggesting that redistribution of PCP from the testis is too slow to benefit from a limited dose of antibody. These results indicate that anti-PCP IgG can preferentially protect the brain for approximately 4 weeks after IgG administration, even when the antibody binding capacity should have been saturated with continuously administered PCP.
Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. (1996)

When phagocyte CR3 binds to iC3b on bacteria or yeast, phagocytosis and degranulation are triggered because of simultaneous recognition of iC3b via a CD11b I-domain binding site and specific microbial polysaccharides via a lectin site located COOH-terminal to the I-domain. By contrast, when phagocyte or natural killer (NK) cell CR3 adheres to iC3b on erythrocytes or tumor cells that lack CR3-binding membrane polysaccharides, neither lysis nor cytotoxicity are stimulated. This investigation showed that soluble CR3-specific polysaccharides such as beta-glucan induced a primed state of CR3 that could trigger killing of iC3b-target cells that were otherwise resistant to cytotoxicity. Anti-CR3 added before sugars prevented priming, whereas anti-CR3 added after sugars blocked primed CR3 attachment to iC3b-targets. Polysaccharide priming required tyrosine kinase(s) and a magnesium-dependent conformational change of the I-domain that exposed the CBRM1/5 activation epitope. Unlike LPS or cytokines, polysaccharides did not up-regulate neutrophil CR3 expression nor expose the mAb 24 reporter epitope representing the high affinity ICAM-1-binding state. The current data apparently explain the mechanism of tumoricidal beta-glucans used for immunotherapy. These polysaccharides function through binding to phagocyte or NK cell CR3, priming the receptor for cytotoxicity of neoplastic tissues that are frequently targeted with iC3b and sparing normal tissues that lack iC3b.
Visibility-based prefetching for interactive out-of-core rendering (2003)

We present a new visibility-based prefetching algorithm for interactive out-of-core rendering of large models on an inexpensive PC. Using an approximate visibility technique, we can very accurately and efficiently determine which geometry will be visible in the near future and prefetch that geometry from disk before it must be rendered. Our prefetching algorithm is a key part of a visualization system capable of rendering a 13-million triangle model with 99% accuracy at interactive frame rates. Our prefetching algorithm is the first of its kind to be based on a from-point visibility technique, and enables interactive rendering on a commodity PC, as opposed to expensive high-end graphics workstations or parallel machines.
A Functional Analysis Reveals Dependence on the Anaphase-Promoting Complex for Prolonged Life Span in Yeast (2004)

Defects in anaphase-promoting complex (APC) activity, which regulates mitotic progression and chromatin assembly, results in genomic instability, a hallmark of premature aging and cancer. We investigated whether APC-dependent genomic stability affects aging and life span in yeast. Utilizing replicative and chronological aging assays, the APC was shown to promote longevity. Multicopy expression of genes encoding Snf1p (MIG1) and PKA (PDE2) aging-pathway components suppressed apc5CA phenotypes, suggesting their involvement in APC-dependent longevity. While it is known that PKA inhibits APC activity and reduces life span, a link between the Snf1p-inhibited Mig1p transcriptional modulator and the APC is novel. Our mutant analysis supports a model in which Snf1p promotes extended life span by inhibiting the negative influence of Mig1p on the APC. Consistent with this, we found that increased MIG1 expression reduced replicative life span, whereas mig1Delta mutations suppressed the apc5CA chronological aging defect. Furthermore, Mig1p and Mig2p activate APC gene transcription, particularly on glycerol, and mig2Delta, but not mig1Delta, confers a prolonged replicative life span in both APC5 and acp5CA cells. However, glucose repression of APC genes was Mig1p and Mig2p independent, indicating the presence of an uncharacterized factor. Therefore, we propose that APC-dependent genomic stability is linked to prolonged longevity by the antagonistic regulation of the PKA and Snf1p pathways.
The diversity of subunit composition in nAChRs: Evolutionary origins, physiologic and pharmacologic consequences (2002)

Nicotinic acetylcholine receptors are made up of homologous subunits, which are encoded by a large multigene family. The wide number of receptor oligomers generated display variable pharmacological properties. One of the main questions underlying research in molecular pharmacology resides in the actual role of this diversity. It is generally assumed that the observed differences between the pharmacology of homologous receptors, for instance, the EC(50) for the endogenous agonist, or the kinetics of desensitization, bear some kind of physiologic relevance in vivo. Here we develop the quite challenging point of view that, at least within a given subfamily of nicotinic receptor subunits, the pharmacologic variability observed in vitro would not be directly relevant to the function of receptor proteins in vivo. In vivo responses are not expected to be sensitive to mild differences in affinities, and several examples of functional replacement of one subunit by another have been unravelled by knockout animals. The diversity of subunits might have been conserved through evolution primarily to account for the topologic diversity of subunit distribution patterns, at the cellular and subcellular levels. A quantitative variation of pharmacological properties would be tolerated within a physiologic envelope, as a consequence of a near-neutral genetic drift. Such a "gratuitous" pharmacologic diversity is nevertheless of practical interest for the design of drugs, which would specifically tackle particular receptor oligomers with a defined subunit composition among the multiple nicotinic receptors present in the organism.
Inhibition of suppressor-cell activity by cyclophosphamide in patients with malignant melanoma. (1987)

Twenty patients with malignant melanoma were treated with cyclophosphamide (100, 300 or 500 mg/m2 i.v.) in pilot studies to determine whether such treatment affected suppressor-cell activity. Delayed hypersensitivity to dinitrochlorobenzene and other recall antigens, the serological response to primary immunization with pneumococcal or influenza virus antigens, and the serological response to melanoma antigens were found to be normal and were not changed by cyclophosphamide (Cy) treatment. In vitro assays for production of antibodies against sheep red blood cell (SRBC) antigens, reactivity in the mixed lymphocyte culture reaction, and induction of suppressor cells by Concanavalin-A (Con-A) yielded abnormal results as a consequence of increased suppressor-cell activity in eleven, three, and nine patients, but no concordance was seen between results with the three assays prior to treatment. After treatment with Cy, the results of these tests became normal in seven, three, and seven of the patients with previously abnormal results, independent of the dose given. Examining all patients as a group, a statistically significant effect was seen after treatment with Cy on days 14 and 21 in the assay for the production of antibodies against SRBC, and days 7, 14, 21, 28, and 35 in the assay for Con-A-induced suppressor cells. The decrease in suppressor-cell activity was largely restricted to patients who showed increased suppressor-cell activity prior to treatment with Cy. Our results suggest that increased suppressor-cell activity in patients with malignant melanoma does not affect immune reactions generally but is selective, and that the anti-suppressor-cell effect of Cy is restricted to reactions with increased suppressor-cell activity to start. Based on these results, attempts at increasing the immune response to melanoma antigen vaccines administered between 7 and 35 days after treatment with Cy seem justified.
Exclusive nuclear location of estrogen receptors in Squalus testis. (1985)

An estrogen (E)-binding molecule having both occupied and unoccupied sites is restricted to nuclear subfractions in the testis of the spiny dogfish (Squalus acanthias). We investigated the hypothesis that a species characterized by high body-fluid osmolarity (1010 mosM) has an estrogen receptor (ER) that binds to chromatin with high affinity and consequently resists redistribution during tissue processing. Although the steroid binding and sedimentation properties of the Squalus nuclear ER conformed to those of classical ER, its elution maximum from DNA-cellulose was unusually high (0.55 M NaCl). A tendency to adhere tightly to cell nuclei was reflected in the high salt concentration (0.43 M KCl) required to extract 50% of the receptors from the nuclear compartment during homogenization and in the stability of the nuclear ER population in the presence of high concentrations of a nonionic solute (urea) or increased buffer volume. Mixing and redistribution experiments showed that nuclear ER could be quantitatively and qualitatively measured in cytosolic extracts, ruling out the possibility that soluble receptors were being masked. Although Squalus oviduct ER was similar to that of testis, ER in the testis and liver of a related elasmobranch (Potamotrygon) that maintains osmotic equilibrium at 300 mosM more closely resembled mammalian ER in its elution maximum from DNA-cellulose (0.22 M NaCl) and cytosolic/nuclear ratios in low-salt buffers. We conclude that Squalus testis has a single ER pool located exclusively in the nuclear compartment. These observations support a revised concept of steroid action and further indicate that the chromatin affinity of the hormone-ER complex is an important factor in determining subfractional distribution during tissue processing.
Cerebral Ischemia–Reperfusion Injury in Rats—A 3 T MRI Study on Biphasic Blood–Brain Barrier Opening and the Dynamics of Edema Formation (2009)

Serial magnetic resonance imaging (MRI) was performed to investigate the temporal and spatial relationship between the biphasic nature of blood-brain barrier (BBB) opening and, in parallel, edema formation after ischemia-reperfusion (I/R) injury in rats. T(2)-weighted imaging combined with T(2)-relaxometry, mainly for edema assessment, was performed at 1 h after ischemia, after reperfusion, and at 4, 24 and 48 h after reperfusion. T(1)-weighted imaging was performed before and after gadolinium contrast at the last three time points to assess BBB integrity. The biphasic course of BBB opening with a significant reduction in BBB permeability at 24 h after reperfusion, associated with a progressive expansion of leaky BBB volume, was accompanied by a peak ipsilateral edema formation. In addition, at 4 h after reperfusion, edema formation could also be detected at the contralateral striatum as determined by the elevated T(2)-values that persisted to varying degrees, indicative of widespread effects of I/R injury. The observations of this study may indicate a dynamic temporal shift in the mechanisms responsible for biphasic BBB permeability changes, with complex relations to edema formation. Stroke therapy aimed at vasogenic edema and drug delivery for neuroprotection may also be guided according to the functional status of the BBB, and these findings have to be confirmed in human stroke.