gebhart/patrepeval huggingface dataset:
Structural requirements for antioxidative and anti-inflammatory properties of apolipoprotein A-I mimetic peptides (2007)

Recently, attention has been focused on pharmacological treatments that increase HDL cholesterol to prevent coronary artery disease. Despite three decades of extensive research of human apolipoprotein A-I (apoA-I), the major protein component of HDL, the molecular basis for its antiatherogenic and anti-inflammatory functions remain elusive. Another protein component of HDL, apoA-II, has structural features similar to those of apoA-I but does not possess atheroprotective properties. To understand the molecular basis for the effectiveness of apoA-I, we used model synthetic peptides. We designed analogs of the class A amphipathic helical motif in apoA-I that is responsible for solubilizing phospholipids. None of these analogs has sequence homology to apoA-I, but all are similar in their lipid-associating structural motifs. Although all of these peptide analogs interact with phospholipids to form peptide:lipid complexes, the biological properties of these analogs are different. Physical-chemical and NMR studies of these peptides have enabled the delineation of structural requirements for atheroprotective and anti-inflammatory properties in these peptides. It has been shown that peptides that interact strongly with lipid acyl chains do not have antiatherogenic and anti-inflammatory properties. In contrast, peptides that associate close to the lipid head group (and hence do not interact strongly with the lipid acyl chain) are antiatherogenic and anti-inflammatory. Understanding the structure and function of apoA-I and HDL through studies of the amphipathic helix motif may lead to peptide-based therapies for inhibiting atherosclerosis and other related inflammatory lipid disorders.
Detection of Isoflavones in Seedling Subterranean Clover (1991)

Reproductive disorders in sheep ( Ovis ones ) have been linked to ingestion of subterranean clovers ( Trifolium brachycalycinum Katzn. &amp; Morley, T. subterraneum L., and T. yanninicum Katzn. &amp; Morley) containing high levels of the phytoestrogenic isoflavones formononetin (7‐hydroxy‐4‐methoxyisoflavone; FM), genistein (5,7,4‐trihydroxyisoflavone; GE), and biochanin A (5,7‐dihydroxy‐4‐methoxyisoflavone; BA). Breeding programs involving subterranean clovers should include selection for low isoflavone concentrations. Our objective was to develop a seedling assay that would predict field levels of FM, GE, and BA in subterranean clover. Five subterranean clover cultivars were grown in the field at Overtoil, TX, over a 3‐yr period (1985, 1986, and 1987); leaf samples were analyzed for FM, GE, and BA. The same cultivars were used to test potential seedling assays. Six seedling growth stages were used: ungerminated seed (UGS), swelled seed (SWS), seedlings after 48 h germination with testa removed (2DAYS), seedlings grown in distilled water for 8 d (8DAYS), seedlings grown in the greenhouse for 42 d (42DAYS), and regrowth harvested 21 d later (REGRO). Tissue samples were extracted with methanol (7 d at 5 °C) and analyzed using high performance liquid chromatography HPLC techniques. Field‐grown samples of each of the cultivars were consistent with previously known values for FM, GE, and BA. Only trace amounts of isoflavones were detected in the UGS and SWS treatments. The 2DAYS and 8DAYS seedling treatments were highly variable and inconsistent in regard to isoflavone content compared with field data for the cultivars. Regression equations using the 42DAYS and REGRO treatments were accurate in their prediction of FM, BA, and total isoflavones in field‐grown subterranean clover. The 42DAYS and REGRO treatments for determining isoflavone content of subterranean clover seedlings could be used to rank germplasm for potential phytoestrogen effects.
Activation requirements for CD4+ T cells differing in CD45R expression (1992)

Murine CD4+ T cells can be subdivided into naive and memory T cells based on surface phenotype, on recall response to Ag, and on differences in activation requirements. Furthermore, several studies have shown that two signals are required for CD4+ T cell activation; one signal is provided by occupancy of the TCR and the other signal is provided by the APC. In this report, analysis of naive and memory CD4 T cells, separated on the basis of CD45 isoform expression, has shown that their requirements for two signals differ. Activation of memory CD4 T cells to proliferate and secrete IL-2/IL-4 only required occupancy of the TCR complex, whereas activation of naive CD4 T cells required an APC-derived signal as well. Moreover, the signal induced by anti-CD3 antibodies differs from the signal provided by anti-V beta cross-linking of the TCR because both antibodies activate memory CD4 T cells but only anti-CD3 activates naive CD4 T cells. Together these data suggest that the consequence of stimulation through the TCR/CD3 signal complex differs between memory and naive CD4 T cells.
Differential expression of mGluR5 metabotropic glutamate receptor mRNA by rat striatal neurons (1995)

Metabotropic glutamate receptors (mGluRs) mediate the effects of glutamate neurotransmission on intracellular second messenger systems. Among the seven distinct mGluR receptor isoforms currently identified, the mGluR5 isoform is expressed particularly prominently in the striatum, where it may contribute to neuronal plasticity, motor behaviors, and excitotoxic injury. mGluR5 mRNA expression in striatal enkephalinergic, somatostatinergic, and cholinergic neurons was examined using double label in situ hybridization techniques. mGluR5 expression is abundant in a large number of medium-sized striatal cells but is absent in a significant minority of neurons. Double label in situ hybridization with 35S-dATP- and digoxygenin-dUTP-tailed oligonucleotide probes demonstrated that mGluR5 message is highly expressed by enkephalinergic striatal neurons but is not detectable in cholinergic or somatostatin interneurons. In addition, some nonenkephalin, presumably substance P, neurons were also strongly labeled for mGluR5. The differential expression of mGluR5 in striatal projection neurons vs. interneurons may contribute to the selective vulnerability of these neurons to disease processes.
Droplet microfluidics (2008)

Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of "digital fluidic" operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as microreactors ranging from the nano- to femtoliter range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. This review will focus on the various droplet operations, as well as the numerous applications of the system. Due to advantages unique to droplet-based systems, this technology has the potential to provide novel solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.
Favorable effects of the lipid-lowering and platelet antiaggregant Plafibride on the aging process of mice of the C57bl/6J strain. (1983)

It is known that an excessive intake of lipids and raised lipid levels in the blood accelerate many of the age-dependent pathologies. Therefore, it is probable that the administration of hypolipidemic agents delays to a certain degree the rate of aging. This concept has been experimentally tested in mice of the C57BL/6J strain treated with N-(2-p-chlorophenoxy) methylpropionil)-N'-morfolinomethylurea (Plafibride). The chemical was given in diet pellets at a dose of approximately 180 mg/kg body weight/day. There were no manifestations of toxicity despite the fact that treatment lasted 8 months. On the contrary, it seems that the aging process was favorably influenced since vigor and neuromuscular coordination were somewhat preserved in the treated mice in comparison to the controls. Moreover, old mice treated with Plafibride showed values for body and liver weights that were more similar to those of younger mice. These effects were especially evident in animals fed an hypercaloric diet enriched with fat and sucrose. The present experimental results suggest performing clinical studies for investigation of the effects of long-term treatment with Plafibride on the physiological and pathological manifestations of human aging.
Synthesis and photochemistry of photolabile N-glycine derivatives and effects of one on the glycine receptor (1992)

Three photolabile precursors of glycine containing a photosensitive 2-nitrobenzyl moiety attached to the amino group have been synthesized. When exposed to ultraviolet radiation between 308 and 350 nm, the compounds photolyze to release glycine, an important inhibitory neurotransmitter in the central nervous system. The identification of glycine as a photolysis product was determined by two different methods: separation of the photolyzed sample by thin-layer chromatography followed by a reaction with ninhydrin, and recognition of derivatized glycine using the Waters pico-tag method in conjunction with high-performance liquid chromatography. The photolysis of these compounds at 22 degrees C has been investigated, and the rate of decay of a transient intermediate in the reaction, which is assumed to reflect product release, has been measured. For N-(alpha-carboxy-2-nitrobenzyl)glycine this decay rate was found to be 940 s-1 at pH 6.8 and 600 s-1 at pH 7.5. Additionally, this compound was found to exhibit biological activity upon photolysis; cultured mouse spinal cord cells containing neuronal glycine receptors were used to detect the glycine liberation. The approach adopted here is useful in demonstrating the utility of photolabile precursors of neurotransmitters that have the protecting group linked to the neurotransmitter through the amino group. The rapid photolysis of such compounds to release free neurotransmitter is valuable in gaining access to chemical kinetic studies of neurotransmitter receptors. Previously, such studies have been limited because the available methods for neurotransmitter delivery did not give a sufficiently high time resolution.
Targeting cellular metabolism to improve cancer therapeutics (2013)

The metabolic properties of cancer cells diverge significantly from those of normal cells. Energy production in cancer cells is abnormally dependent on aerobic glycolysis. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics such as increased fatty acid synthesis and increased rates of glutamine metabolism. Emerging evidence shows that many features characteristic to cancer cells, such as dysregulated Warburg-like glucose metabolism, fatty acid synthesis and glutaminolysis are linked to therapeutic resistance in cancer treatment. Therefore, targeting cellular metabolism may improve the response to cancer therapeutics and the combination of chemotherapeutic drugs with cellular metabolism inhibitors may represent a promising strategy to overcome drug resistance in cancer therapy. Recently, several review articles have summarized the anticancer targets in the metabolic pathways and metabolic inhibitor-induced cell death pathways, however, the dysregulated metabolism in therapeutic resistance, which is a highly clinical relevant area in cancer metabolism research, has not been specifically addressed. From this unique angle, this review article will discuss the relationship between dysregulated cellular metabolism and cancer drug resistance and how targeting of metabolic enzymes, such as glucose transporters, hexokinase, pyruvate kinase M2, lactate dehydrogenase A, pyruvate dehydrogenase kinase, fatty acid synthase and glutaminase can enhance the efficacy of common therapeutic agents or overcome resistance to chemotherapy or radiotherapy.
Enhancing Intrinsic Cochlear Stress Defenses to Reduce Noise‐Induced Hearing Loss (2002)

These data lend further support to the growing body of evidence that oxidative stress, generated in part by glutamate excitotoxicity, impaired mitochondrial function and GSH depletion causes cochlear injury induced by noise. Enhancing the cellular oxidative stress defense pathways in the cochlea eliminates noise-induced cochlear injury. The data also suggest strategies for therapeutic intervention to reduce NIHL clinically.
Nonsense-Mediated mRNA Decay and Ubiquitin–Proteasome System Regulate Cardiac Myosin-Binding Protein C Mutant Levels in Cardiomyopathic Mice (2009)

These data reveal (1) an unanticipated complexity of the expression of a single point mutation in the whole animal and (2) the involvement of both nonsense-mediated mRNA decay and the ubiquitin-proteasome system in lowering the level of mutant proteins.
Two-photon wave-packet interferometry (1994)

The excitation of a molecule by a short pulse creates a wave packet whose motion depends on the nuclear forces of the excited electronic state. The properties of such a packet can be studied interferometrically. This is done by exposing the molecule to two identical pulses delayed from each other. Two packets are thus created and the excited state population has a term which depends on the interference between them. This interference population is a quantum effect and its dependence on the delay time reflects the coherence properties of the packet and is very sensitive to the potential energy surface. In this paper, we examine the use of wave-packet interferometry to study the dynamic properties of packets created by two-photon absorption. We find several interference populations since the packets created by two-photon absorption interfere with each other and with packets created by absorption of one photon from each pulse. The single interference terms contain different physical information and we discuss how each can be measured separately. This method provides a sensitive way for studying the dynamic properties of high energy electronic states that can be reached by two-photon absorption.
A system for quantifying dynamic protein interactions defines a role for Herceptin in modulating ErbB2 interactions (2006)

The orphan receptor tyrosine kinase ErbB2 is activated by each of the EGFR family members upon ligand binding. However, difficulties monitoring the dynamic interactions of the membrane receptors have hindered the elucidation of the mechanism of ErbB2 activation. We have engineered a system to monitor protein-protein interactions in intact mammalian cells such that different sets of protein interactions can be quantitatively compared. Application of this system to the interactions of the EGFR family showed that ErbB2 interacts stably with the EGFR and ErbB3, but fails to spontaneously homooligomerize. The widely used anti-cancer antibody Herceptin was found to effectively inhibit the interaction of the EGFR and ErbB2 but not to interfere with the interaction of ErbB2-ErbB3. Treatment of cells expressing EGFR and ErbB2 with Herceptin results in increased EGFR homooligomerization in the presence of EGF and a subsequent rapid internalization and down-regulation of the EGFR. In summary, the protein interaction system described here enabled the characterization of ErbB2 interactions within the biological context of the plasma membrane and provides insight into the mechanism of Herceptin action on cells overexpressing ErbB2.
Biogenesis of the apical endosome–lysosome complex during differentiation of absorptive epithelial cells in rat ileum (1991)

Absorptive cells of the neonatal rat ileum have an elaborate apical endocytic complex consisting of tubular and vesicular endosomes, multivesicular bodies (MVB), and a giant lysosomal vacuole. This system develops rapidly over the last 3 days (20-22) of gestation. We followed the assembly of this complex by ultrastructural analysis and immunocytochemistry using antigenic markers for microvilli, endosomal tubules and lysosomal membranes. At 19 days gestation, low levels of lactase appeared on microvilli but specialized apical endosomal tubules and lysosomes were absent. At 20 days, expression of microvillar lactase increased and the endosomal marker entubin appeared, in parallel with the appearance of specialized apical endosomal tubules. The compartments of the apical endosome-lysosome system were assembled sequentially after differentiation of the apical plasma membrane domains; first endosomal tubules and vesicles, followed by MVB, and ending with the assembly of the giant lysosome shortly after birth. During early stages of the assembly process, membrane components of the tubular endosomes and lysosomes appeared in the apical plasma membrane before being restricted to their respective intracellular compartments.
Inhibitory action of peptide YY on gastric acid secretion (1987)

The purpose of this study is to investigate the effect of peptide YY (PYY) on pentagastrin-, histamine-, and bethanechol-stimulated gastric acid secretion and the possible mechanisms by which PYY inhibits gastric acid secretion. Six mongrel dogs with chronic gastric and duodenal fistulas were given an intravenous infusion of pentagastrin (0.5 microgram . kg-1 . h-1), histamine (18 micrograms . kg-1 . h-1), or bethanechol (80 micrograms . kg-1 . h-1) either alone or simultaneously with intravenous PYY (100, 200, 400, pmol . kg-1 . h-1). PYY (100, 200, 400 pmol . kg-1 . h-1) inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner. PYY (400 pmol . kg-1 . h-1) did not depress bethanechol-stimulated gastric acid secretion. PYY (400 pmol . kg-1 . h-1) also failed to inhibit histamine-stimulated gastric acid secretion. Furthermore, PYY inhibit pentagastrin-stimulated gastric acid secretion in the face of atropine, vagotomy, or indomethacin treatment. These findings indicate that the inhibitory action of PYY on gastric acid secretion is in part independent of long and short cholinergic pathways. These findings also indicate that the inhibitory mechanism of PYY is independent of prostaglandin synthesis. Our findings are discussed in relation to previous reports regarding the effects of PYY on gastric acid secretion.
Thiophene/cyclopentadiene regular copolymers from electrochemical oxidation of dithienylcyclopentadienes (2002)

Anodic coupling to polymer of some dithienylcyclopentadienes has been performed in acetonitrile. The polymers have been characterized by cyclic voltammetry, UV-vis, MALDI mass and FT-IR spectroscopies, and in situ conductivity. Nonsubstituted dithienylcyclopentadiene undergoes coupling both at the thiophene α-position and at the internal cyclopentadiene sites with the production of an insoluble polymer corresponding to a tetrameric formulation. Protection of the cyclopentadiene 5 position with alkyl chains has allowed the production of regularly α-coupled polymers. The optical gap of poly(dithienylcyclopentadiene) has been evaluated as 2.2 eV, i.e., close to that of polythiophene (2.3 eV). Structure of 4b1.
A novel apoptosis research method with imaging‐combined flow cytometer and HITC or IR‐125 staining (2002)

The most commonly used methods for apoptotic research include terminal transferase-mediated dUTP nick end-labeling, annexin V testing of phosphatidylserine translocation from the inner leaflet to the outer plasma membrane by flow cytometry, DNA electrophoresis, and cell morphology. These methods provide apoptotic information from different aspects. To find a new way in apoptosis research and potential clinical application, we recently developed a novel method with an imaging-combined flow cytometer (IFC) and an innovative cell staining process by using 2-[7-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)-1,3,5-heptatrienyl]-1,3,3-trimethyl-3H-indolium iodide (HITC) and 2-[7-[1,3-dihydro-1,1-dimethyl-3-(4-sulfobutyl)-2H-benz[e]indol-2-ylidene]-1,3,5-heptatrienyl]-1,1-dimethyl-3-(4-sulfobutyl)-1H-benz[e]indolium hydroxide, inner salt, sodium salt (IR-125). The IFC used in the research is a new generation of cytometry designed for simultaneous observations of cell populations and images. This is possible because the IFC is equipped with dual laser beams, one argon and one infrared. A promyelocytic leukemia cell line, HL-60, was used in the research. The cells were stained with our newly developed HITC or IR-125 staining method and a traditional nucleic acid dye, propidium iodide. The cells stained with HITC or IR-125 appeared completely dark in the IFC image window before washing. Phosphate buffered saline wash did not change the cell appearance. A wash with 50% methanol caused the cells to have a clear cell image with bright nuclei on the IFC. To obtain apoptotic cells, we treated the HL-60 cells with 0.15 microM of camptothecin (CAM), a topoisomerase I inhibitor and experimental apoptosis inducer, for 4 h. The control showed larger round cells with bright nuclei and one to three dark nucleoli. The CAM-induced apoptotic cells were smaller, with fragmented and condensed nuclei on the IFC. These appearances were identical to the cell morphology of with light and electron microscopy. We used other methods including FACScan and DNA electrophoresis to confirm the apoptotic changes after CAM treatment and compared them with the IFC method. In addition, we found that the novel method with the IFC and HITC or IR-125 staining can show not only cell apoptotic changes but also peripheral blood cell populations and images simultaneously. This study suggests many potential applications of the IFC and this novel staining method in other cellular biological researches and clinical assays.
Marrow stromal cell commitment to mineralization under the effect of a prolyl hydroxylase inhibitor (1994)

Mitochondrial response to the effect of a hydroxylase (PH) inhibitor was tested in marrow stromal cells during stimulation of osteoprogenitor cell (OPC) differentiation. The rationale for this was to explore pathways of regulatory interactions between procollagen synthesis and mitochondrial respiration that could be linked to the commitment of OPCs to mineralization. Stimulated OPCs exposed to the PH inhibitor cis-hydroxyproline (cis-HP), compared to the noninhibiting isomer trans-HP, for 11 days showed a dose-dependent decrease in cell proliferation, the surviving cells showed increased alkaline phosphatase activity. Trans-HP did not influence the cis-HP effect on ALP and on proliferation arrest. Short time exposures, 2-3 days, to cis-HP at different periods suggested that Days 0-3 and 3-5 were critical for the commitment to Day 21 mineralization of OPCs. On Days 0-3 cells were most sensitive to cis-HP, since on Day 11, 8 days after removal of cis-HP, they were too scarce to be counted by the staining method. However, the presence of 5.0 mM cis-HP in the cultures during Days 3-5 has induced on Day 21 close to 24-fold more mineralization/cell than controls, compared to the trans-HP effect, which was only close to 3-fold. The presence of cis-HP in the cultures on Days 0-3 has augmented the mitochondrial Day 3 retention of rhodamine 123 (Rho) in the stromal cells, relative to controls, compared to the presence of trans-HP. However, the presence of cis-HP during Days 3-5 or 3-6 resulted in lower Day 5 Rho retention, relative to controls, which was not significantly different from the retention that resulted from trans-HP. Since Rho retention is related to the final result of aerobic respiration level, these results are interpreted as a cis-HP inhibitory effect on procollagen peptidyl-proline hydroxylation, which may in turn release oxygen surpluses, to be available for mitochondrial consumption. The fall in Rho retention responses to cis-HP between Days 0-3 and 3-5 is suggesting either abrupt decrease in proline hydroxylation or poor mitochondrial sensitivity to oxygen in Day 3-5 cultures.