gebhart/patrepeval huggingface dataset:
A COMPARATIVE STUDY OF HYDROXYINDOLE OXIDASES (1960)

A comparative study has been carried out of the oxidation of 5-hydroxytryptamine and related compounds by the oxidase present in the gill plates of Mytilus edulis and of caeruloplasmin, the copper containing oxidase of mammalian plasma. Both preparations oxidized indole derivatives carrying a hydroxyl group in the 4-, 5-, 6-, or 7- position. The oxidation of bufoteni ne was compared with that of its 4- and 6-hydroxy analogues; the 4-hydroxy analogue is psil ocine, a naturally occurring hallucinogenic compound. Bufotenine and the 6-hydroxy analogue were oxidized by both preparations with the formation of brown pigments; psilocine was more rapidly oxidized with the appearance of a blue colour. 4-Hydroxytryptamine and 7-hydroxytryptamine were also oxidized, the former with the formation of a blue compound. The N-1-methyl derivatives of both bufotenine and psilocine were also oxidized. The Mytilus preparation acted also on 4-, 5-, and 7-hydroxytryptophan and on 5-hydroxyindole, none of which was oxidized by caeruloplasmin. The Mytilus enzyme also oxidized 5-hydroxyindoleacetic acid. Paraphenylenediamine, a very good substrate of caeruloplasmin, was much more slowly oxidized by the gill plate enzyme. The evidence suggests that the two enzymes catalyse the same reactions, but that the substrate specificity of the mammalian oxidase is somewhat more restricted. Both enzymes are "hydroxyindole oxidases," not specific for 5-hydroxyindoles alone. Inhibitors of the Mytilus oxidase included inhibitors of copper enzymes but not edetate or carbon monoxide. The action of pig serum on 5-hydroxytryptamine was due to caeruloplasmin and not to amine oxidase.
DNA-binding domain of bovine papillomavirus type 1 E1 helicase: structural and functional aspects (1993)

The E1 protein of bovine papillomavirus type 1 is a multifunctional enzyme required for papillomaviral DNA replication. It assists in the initiation of replication both as a site-specific DNA-binding protein and as a DNA helicase. Previous work has indicated that at limiting E1 concentrations, the E2 protein is required for efficient E1 binding to the replication origin. In this study, we have defined the domain of the E1 protein required for site-specific DNA binding. Experiments with a series of truncated proteins have shown that the first amino-terminal 299 amino acids contain the DNA-binding domain; however, the coterminal M protein, which is homologous to E1 for the first 129 amino acids, does not bind origin DNA. A series of small internal deletions and substitution mutations in the DNA-binding domain of E1 show that specific basic residues in this region of the protein, which are conserved in all E1 proteins of the papillomavirus family, likely play a direct role in binding DNA and that a flanking conserved hydrophobic subdomain is also important for DNA binding. A region of E1 that interacts with E2 for cooperative DNA binding is also retained in carboxy-terminal truncated proteins, and we show that the ability of full-length E1 to complex with E2 is sensitive to cold. The E1 substitution mutant proteins were expressed from mammalian expression vectors to ascertain whether site-specific DNA binding by E1 is required for transient DNA replication in the cell. These E1 proteins display a range of mutant phenotypes, consistent with the suggestion that site-specific binding by E1 is important. Interestingly, one E1 mutant which is defective for origin binding but can be rescued for such activity by E2 supports significant replication in the cell.
Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes (2006)

In response to hypoxia, hypoxia-inducible factors act as the primary proangiogenic triggers by regulating transcription levels of target genes, including VEGF. However, little is known about the specific factors that control other components of the angiogenic process, particularly formation of matrix scaffolds that promote adhesion and migration of endothelial cells. We show that in the postnatal mouse retina, the orphan nuclear receptor tailless (Tlx) is strongly expressed in the proangiogenic astrocytes, which secrete VEGF and fibronectin. Tlx expression by retinal astrocytes is controlled by oxygen concentration and rapidly downregulated upon contact with blood vessels. In mice null for Tlx, retinal astrocytes maintain VEGF expression; however, the extracellular assembly of fibronectin matrices by astrocytes is severely impaired, leading to defective scaffold formation and a complete failure of normal retinal vascular development. This work identifies Tlx as an essential component of the molecular network involved in the hypoxia-inducible proangiogenic switch in retinal astrocytes.
Photochemical internalization of a peptide nucleic acid targeting the catalytic subunit of human telomerase. (2003)

Because peptide nucleic acids (PNAs) are poorly taken up by mammalian cells, strategies need to be developed for their intracellular delivery. In the present study, we demonstrated the possibility to efficiently release a naked PNA targeting the catalytic component of human telomerase reverse transcriptase (hTERT-PNA) into the cytoplasm of DU145 prostate cancer cells through the photochemical internalization approach. After light exposure, cells treated with the hTERT-PNA and photosensitizer TPPS(2a) showed a marked inhibition of telomerase activity and a reduced cell survival, which was not observed after treatment with hTERT-PNA alone. Moreover, in a direct comparison, photochemical internalization technology proved to be more efficient to internalize the hTERT-PNA than an HIV-Tat protein-based approach.
Contribution of the ABC Transporters Bcrp1 and Mdr1a/1b to the Side Population Phenotype in Mammary Gland and Bone Marrow of Mice (2005)

The ability of cells to export Hoechst 33342 can be used to identify a subpopulation of cells (side population [SP]) with characteristics of stem cells in many tissues. The ATP-binding cassette transporters Bcrp1 (Abcg2) and Mdr1a/1b (Abcb1a/1b) have been implicated as being responsible for this phenotype. To further explore the involvement of these transporters in the SP phenotype, we have generated Bcrp1/Mdr1a/1b triple knockout mice and studied the effect of their absence on the SP in bone marrow and mammary gland. Whereas in bone marrow Bcrp1 was almost exclusively responsible for the SP, both transporters contributed to the SP phenotype in the mammary gland, where their combined absence resulted in a nearly complete loss of SP. Interestingly, bone marrow of Mdr1a/1b-/- mice frequently displayed an elevated SP, which was reversible by the Bcrp1 inhibitor Ko143, suggesting that Bcrp1 can compensate for the loss of Mdr1a/1b in bone marrow.
Synergy between the T3/antigen receptor complex and Tp44 in the activation of human T cells. (1986)

In addition to the T3/antigen receptor complex (T3/Ti), other T cell surface molecules participate in early events involved in human T cell activation. In this report we document that monoclonal antibody 9.3, which recognizes a 90,000 dalton homodimer expressed on human T cells, synergizes with ligands reacting with T3/Ti to activate purified T cells and Jurkat, a human T cell leukemic line. Unlike phorbol myristate acetate (PMA), 9.3 was able to synergize only with anti-T3 or anti-Ti if these antibodies were immobilized. Moreover, 9.3 failed to synergize with the calcium ionophore ionomycin. At high concentrations only, 9.3 could synergize with PMA in the activation of Jurkat and a T3/Ti negative mutant of Jurkat. At such high concentrations of 9.3, small transient increases in cytoplasmic free calcium ((Ca++)i) were detected in quin 2-loaded Jurkat cells. This increase in (Ca++)i was the result of release of internal stores of calcium. 9.3 induced the hydrolysis of polyphosphoinositides, albeit the magnitude of inositol phosphates generated in response to 9.3 was substantially less than that observed with anti-Ti. No effect on pkC translocation was observed in Jurkat cells stimulated with 9.3. Although the small increase in (Ca++)i induced by 9.3 may account for its synergy with PMA, this effect is unlikely to account for the more potent synergistic effect observed with 9.3 and phytohemagglutinin or immobilized anti-T3 and anti-Ti antibodies.
Platelet-derived growth factor receptor immunoreactivity in mesothelioma and nonneoplastic mesothelial cells in serous effusions. (1995)

Expression of the platelet-derived growth factor receptor (PDGFR) was detected by immunocytochemistry in normal and malignant mesothelial cells from 14 benign effusions and 22 mesotheliomas. Two well-characterized antireceptor monoclonal antibodies to the PDGFR alpha-subunit (PR292) and beta-subunit (PR7212) were used. PDGFR alpha-subunit outlined cell membranes intensely in nonneoplastic mesothelial cells, whereas it was focal in mesothelioma and limited to a few cases only. PDGFR beta-subunit was weakly expressed in the cytoplasm of normal mesothelium; in contrast, malignant mesothelial cells showed strong cytoplasmic staining. Our results show that normal mesothelium may be responsive to PDGF by the predominant expression of PDGFR-alpha and less by PDGFR-beta and indicate the presence of growth-stimulation loops in mesothelioma through PDGF/PDGFR-beta interaction. Also, scattered staining for the PDGFR alpha-subunit suggests that a PDGF-A chain/PDGFR-alpha interaction may also be active in mesothelioma cells growing in suspension.
Human CLK2 Links Cell Cycle Progression, Apoptosis, and Telomere Length Regulation (2003)

Mutations in the clk-2 gene of the nematode Caenorhabditis elegans affect organismal features such as development, behavior, reproduction, and aging as well as cellular features such as the cell cycle, apoptosis, the DNA replication checkpoint, and telomere length. clk-2 encodes a novel protein (CLK-2) with a unique homologue in each of the sequenced eukaryotic genomes. We have studied the human homologue of CLK-2 (hCLK2) to determine whether it affects the same set of cellular features as CLK-2. We find that overexpression of hCLK2 decreases cell cycle length and that inhibition of hCLK2 expression arrests the cell cycle reversibly. Overexpression of hCLK2, however, renders the cell hypersensitive to apoptosis triggered by oxidative stress or DNA replication block and gradually increases telomere length. The evolutionary conservation of the pattern of cellular functions affected by CLK-2 suggests that the function of hCLK2 in humans might also affect the same organismal features as in worms, including life span. Surprisingly, we find that hCLK2 is present in all cellular compartments and exists as a membrane-associated as well as a soluble form.
Probing Structural Selectivity of Synthetic Heparin Binding to Stabilin Protein Receptors (2012)

As one of the most widely used drugs worldwide, heparin is an essential anticoagulant required for surgery, dialysis, treatment of thrombosis, cancer, and general circulatory management. Stabilin-2 is a scavenger clearance receptor with high expression in the sinusoidal endothelium of liver. It is believed that Stabilin-2 is the primary receptor for the clearance of unfractionated and low molecular weight heparins in the liver. Here, we identify the modifications and length of the heparin polymer that are required for binding and endocytosis by both human Stabilin receptors: Stabilin-2 and its homolog Stabilin-1 (also found in liver endothelium). Using enzymatically synthesized (35)S-labeled heparan sulfate oligomers, we identified that sulfation of the 3-OH position of N-sulfated glucosamine (GlcNS) is the most beneficial modification for binding and endocytosis via both Stabilin receptors. In addition, our data suggest that a decasaccharide is the minimal size for binding to the Stabilin receptors. These findings define the physical parameters of the heparin structure required for efficient clearance from blood circulation. These results will also aid in the design of synthetic heparins with desired clearance rates.
MET receptor is overexpressed but not mutated in oral squamous cell carcinomas (2001)

Oral squamous cell carcinoma (SCC) is a neoplasm characterized by a high degree of local invasion and an elevated rate of metastasis to cervical lymph nodes. It has been shown that the Hepatocyte Growth Factor/Scatter Factor Receptor Met is constitutively activated in many human tumors of epithelial origin and that it plays a critical role to confer invasive properties to neoplastic cells. Most frequently, Met activation is due to receptor overexpression, but also point mutations in the tyrosine kinase domain can lead to deregulated activation. Here we show that in all the primary tumors examined this receptor is overexpressed. Direct sequencing of Met mRNAs failed to find any activating mutation in its intracellular domain. Moreover, in cell lines derived from squamous cell carcinomas, HGF-induced activation of Met resulted in the acquisition of invasive properties. All together these data suggest that the MET oncogene is involved in progression of squamous cell carcinoma toward an invasive-metastatic behavior.
Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation (2008)

Intracerebroventricular administration of NPY acutely induces insulin resistance of EGP via activation of sympathetic output to the liver.
Nanoporous Membranes Derived from Block Copolymers: From Drug Delivery to Water Filtration (2010)

With nanoscale pores, high porosity, narrow pore size distributions, and tunable chemical and mechanical properties, block copolymers hold tremendous potential as robust, efficient, and highly selective separation membranes. Recent work by Yang et al. illustrates how block copolymers can be employed in the preparation of membranes for use in controlled, long-term, protein-delivery devices. Their work demonstrates that highly efficient and tunable separations are possible with block copolymer membranes. Although significant progress over the past 10 years has advanced the quality, efficacy, and applicability of such membranes, more work is required before benefits are realized for other demanding applications such as water purification.
Improved peptide function from random mutagenesis over short ‘windows’ (1988)

We have applied random mutagenesis over short contiguous residue tracts ('windows') within an active peptide (the alpha-peptide of beta-galactosidase) such that all window residues are replaced simultaneously. A novel technique using mixed synthetic oligonucleotides and selection against an EcoK restriction site has allowed the construction of libraries of mutants for two separate windows, sites A and B. Mutant phenotypes can be easily assessed in vivo by a complementation test, and panels of mutants have been quantitatively tested in vitro. This allowed the rapid probing of structural requirements for each site. The two windows yielded markedly disparate results. Site B was much less stringent in its sequence requirements for significant function than Site A, and mutants with improved function were isolated at Site B alone. In addition, one Site B mutant with wild-type levels of activity showed enhanced stability to heat or a protein denaturant. We propose that short tracts with the characteristics of Site B constitute 'secondary' interaction sites which are more tolerant of sequence diversity. Random manipulation of such secondary sites is thus more likely to yield upmutations for standard or altered environments. Window mutagenesis can in principle be applied to any protein--protein or protein--ligand interaction.
Dietary omega-3 fatty acids lower levels of platelet-derived growth factor mRNA in human mononuclear cells (1993)

Platelet-derived growth factor (PDGF) is a potent mitogen thought to propagate atherosclerosis and other proliferative or inflammatory diseases. Some of these diseases are ameliorated in humans by ingestion of omega-3 fatty acids. We investigated mRNA expression of both PDGF-A and PDGF-B in quiescent peripheral blood mononuclear cells from healthy male volunteers. For this, a highly sensitive, quantitative polymerase chain reaction strategy (3n-PCR) was developed. In contrast to granulocytes, both PDGF-A and PDGF-B mRNAs are expressed in mononuclear cells. This expression occurs at a remarkably constant rate. Moreover, effects of 7 g/d of a 85% omega-3 fatty acid fish oil concentrate were investigated in a 6-week controlled, randomized, observer-blind study in 14 human volunteers, 7 of whom served as controls. omega-3 Fatty acids increased in mononuclear cell phospholipids. We demonstrate for the first time that diet affects human gene regulation. Dietary omega-3 fatty acids downregulate gene expression of both PDGF-A (-66%), and PDGF-B (-70%). This may represent a novel mechanism for the antifibrotic and antiatherosclerotic action of omega-3 fatty acids.
Neural tube closure depends on nitric oxide synthase activity (2005)

Neural tube (NT) closure is a multifactorial process that involves yet unresolved molecular mechanisms. It had been shown previously that high levels of nitric oxide (NO) block the process of NT closure in the chick embryo by inhibiting methionine synthase (MS). The MS inhibition and its effect on NT closure could be alleviated by folic acid, suggesting the involvement of the folate-methionine pathway in the process. Here we test the hypothesis that endogenous nitric oxide synthase (NOS) activity regulates the MS activity required in the process of NT closure. The experiments described here reveal that NOS activity per se, is indeed critical for NT closure in the chick embryo. Inhibition of NOS activity with either 2,4-diamino-6-hydroxypyrimidine (DAHP), which blocks biosynthesis of the NOS co-factor tetrahydrobiopterin (BH4), or with calmidazolium, which blocks calcium-calmodulin binding to NOS, resulted in reduced MS activity and consequently ablated NT closure. Addition of BH4 or the calcium ionophore A23187 restored NOS and MS activities, resulting in NT closure. The results described here imply that NOS and MS activities can serve as functional markers in this developmental process as they are essential in the process of NT closure.
The Chlorella hexose/H+ symporter is a useful selectable marker and biochemical reagent when expressed in Volvox. (1996)

The multicellular obligately photoautotrophic alga Volvox is composed of only two types of cells, somatic and reproductive. Therefore, Volvox provides the simplest model system for the study of multicellularity. Metabolic labeling experiments using radioactive precursors are crucial for the detection of stage- and cell-type-specific proteins, glycoproteins, lipids, and carbohydrates. However, wild-type Volvox lacks import systems for sugars or amino acids. To circumvent this problem, the hexose/H+ symporter (HUP1) gene from the unicellular alga Chlorella was placed under the control of the constitutive Volvox beta-tubulin promoter. The corresponding transgenic Volvox strain synthesized the sugar transporter in a functional state and was able to efficiently incorporate 14C from labeled glucose or glucosamine. Sensitivity toward the toxic glucose/mannose analogue 2-deoxy-glucose increased by orders of magnitude in transformants. Thus we report the successful transformation of Volvox with a gene of heterologous origin. The chimeric gene may be selected for in either a positive or a negative manner, because transformants exhibit both prolonged survival in the dark in the presence of glucose and greatly increased sensitivity to the toxic sugar 2-deoxyglucose. The former trait may make the gene useful as a dominant selectable marker for use in transformation studies, whereas the latter trait may make it useful in development of a gene-targeting system.
Noise Figure of Watt-Class Ultralow-Confinement Semiconductor Optical Amplifiers (2010)

We investigate the noise figure (NF) of high-power semiconductor InGaAsP optical amplifiers (SOAs) based on the slab-coupled optical waveguide (SCOW) concept having both ultralow optical confinement (Γ ~ 0.5%) and low optical loss (α <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">i</sub> ~ 0.5 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> ). At 1550 nm and 5-A current bias, the NF of SCOW amplifier (SCOWA) is 5.5 dB, and the small-signal gain and saturation output power are 13 dB and 0.8 W, respectively. A minimum NF of 4.5 dB is achieved at 2-A bias. These NF results represent the lowest reported for a packaged SOA. Using the measured NF, the population inversion factor ( <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sp</sub> ) of the SCOWA was also estimated. The derived <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sp</sub> values indicate that intervalence band absorption loss, carrier heating, and quasi-bound higher order modes may ultimately limit the noise performance of InGaAsP SOAs.
Acoustical quality in office workstations, as assessed by occupant surveys (2005)

We analyzed acoustic satisfaction in office environments in buildings surveyed by The Center For The Built Environment (CBE). A total of 23,450 respondents from 142 buildings were included in the analysis. Acoustic satisfaction in the CBE survey is a function of satisfaction with both noise and speech privacy. In the database people are significantly more dissatisfied with speech privacy than noise level (P &amp;lt; 0.01). Occupants in private offices are significantly more satisfied with the acoustics than occupants in cubicles (P&amp;lt;0.01). The results shows also that occupants in open office environments are significantly more satisfied with noise level and speech privacy than occupants working in cubicles (P&amp;lt;0.01). Among occupants dissatisfied with acoustics the most prevalent problems are: “People talking on the phone”, “People overhearing private conversations” and “People talking in surrounding offices”. Over 50% of cubicle occupants think acoustics interfere with their ability to get their job done.