gebhart/patrepeval huggingface dataset:
Geraniol interferes with membrane functions in strains ofCandida andSaccharomyces (1988)

Geraniol, an olefinic terpene, was found to inhibit growth of Candida albicans and Saccharomyces cerevisiae strains. Geraniol was shown to enhance the rate of potassium leakage out of whole cells and also was shown by fluorescence polarization to increase C. albicans membrane fluidity. Biophysical studies using differential scanning calorimetry, fluorescence polarization and osmotic swelling of phospholipid vesicles demonstrated that geraniol decreased the phase-transition temperature of dipalmitoylphosphatidylcholine vesicles, affected fluidity throughout the bilayer, particularly the central portion of the bilayers, and caused an increase in bilayer permeability to erythritol. Geraniol may have potential use as an antifungal agent.
FGF binding by extracellular matrix components of Wharton's jelly. (2007)

Our earlier paper has reported that Wharton's jelly is a reservoir of several peptide growth factors, including acidic and basic fibroblast growth factors (aFGF and bFGF, respectively). Both can be extracted by buffered salts solutions in the form of high molecular mass complexes, probably with a component(s) of the extracellular matrix. Both aFGF and bFGF from such extracts hardly penetrate 10% polyacrylamide gels during electrophoresis. Pre-treatment of Wharton's jelly with hyaluronidase slightly increased the extractability of aFGF, but did not affect the extractability of bFGF. In contrast, the pre-treatment of tissue homogenate with bacterial collagenase (2000 U/ml, 37 degrees C, 18 h) increased the extractability of bFGF. The presence of beta-mercaptoethanol in the extracting solutions increased the extractability of both FGFs, but did not release FGFs in their free form, despite reducing the molecular mass of the FGF-containing complexes. We conclude that both aFGF and bFGF are bound through disulphide bonds to a protein component of Wharton's jelly. We propose that ground substance composed mainly of collagen fibrils and hyaluronate molecules, which surrounds the cells of Wharton's jelly, prevents the access of the extracting solution to aFGF and bFGF. Although hyaluronate and collagen do not bind aFGF or bFGF directly, they may constitute a barrier which prevents the dispersion of FGFs in Wharton's jelly. Thus, the high concentration of FGFs around the cells of Wharton's jelly may facilitate the interaction of these factors with membrane receptors, thereby resulting in stimulation of cell division and differentiation, as well as of the synthesis of extracellular matrix components.
Transitions, Glides, and Diphthongs (1961)

The study deals with the formant movements associated with transitions, glides, and diphthongs in spoken American English. The transitional characteristics associated with all initial and final consonant phonemes were studied in a large sample of utterances. The rate of change of the transition from a consonant hub to the steady state vowel formant position and conversely was investigated for vowels which are commonly considered monophthongs. It is assumed that such changes are cues for the perception of the consonants rather than linguistically significant components of the vocalic nucleus. The rate of change associated with syllable nuclei commonly perceived as diphthongs, [ɑɪ], [ɔɪ], [ɑᴜ] was investigated and compared with the changes due to consonant transitions in monophthongs. Criteria are suggested by which the formant movements due to transitions may be distinguished from movements that have linguistic signalling value within the syllable nucleus.
Cimetidine inhibits production of interferon gamma and tumor necrosis factor alpha by splenocytes in aplastic anemic mice. (2001)

Cim could effectively reduce the production of IFN gamma and TNF alpha from splenocytes of AA mice.
Bacillus thuringiensis §-Endotoxin Expressed in Transgenic Nicotiana tabacum Provides Resistance to Lepidopteran Insects (1987)

The crystal proteins, or section sign-endotoxins, of Bacillus thuringiensis are specifically lethal to Lepidopteran insects. We utilized a truncated and modified portion of a cloned crystal protein gene to construct a chimeric gene capable of expression in plant cells. Using an Agrobacterium tumefaciens binary vector system, we then transferred the chimeric toxin gene into tobacco (Nicotiana tabacum cv Havana 425) cells and regenerated recombinant plants. One to several copies per cell of the toxin gene are routinely present in the recombinant plants. Hybridization experiments demonstrated that these plants had a new RNA species of the size expected for the truncated toxin mRNA, and a polypeptide having the mobility expected for the truncated toxin was detected by immunoblotting. Significant variation was found in the levels of toxin-specific RNA expression between different recombinants, but the levels of hybridizing RNA in transformants correlated with the level of toxicity demonstrated against Manduca sexta (tobacco hornworm), and other Lepidopteran insects. The recombinant genes were transmitted to progeny and resistance to insects was maintained, thus demonstrating that the introduction of toxin genes into plants may be a practical method of providing protection against certain insect pests.
From cyclohydrolase to oxidoreductase: Discovery of nitrile reductase activity in a common fold (2005)

The enzyme YkvM from Bacillus subtilis was identified previously along with three other enzymes (YkvJKL) in a bioinformatics search for enzymes involved in the biosynthesis of queuosine, a 7-deazaguanine modified nucleoside found in tRNA(GUN) of Bacteria and Eukarya. Genetic analysis of ykvJKLM mutants in Acinetobacter confirmed that each was essential for queuosine biosynthesis, and the genes were renamed queCDEF. QueF exhibits significant homology to the type I GTP cyclohydrolases characterized by FolE. Given that GTP is the precursor to queuosine and that a cyclohydrolase-like reaction was postulated as the initial step in queuosine biosynthesis, QueF was proposed to be the putative cyclohydrolase-like enzyme responsible for this reaction. We have cloned the queF genes from B. subtilis and Escherichia coli and characterized the recombinant enzymes. Contrary to the predictions based on sequence analysis, we discovered that the enzymes, in fact, catalyze a mechanistically unrelated reaction, the NADPH-dependent reduction of 7-cyano-7-deazaguanineto7-aminomethyl-7-deazaguanine, a late step in the biosynthesis of queuosine. We report here in vitro and in vivo studies that demonstrate this catalytic activity, as well as preliminary biochemical and bioinformatics analysis that provide insight into the structure of this family of enzymes.
New Therapies for Gout (2013)

Gout prevalence is increasing, yet management remains suboptimal. Fortunately, new insights into gout biology are permitting the development of novel, potentially more effective strategies for both gouty inflammation and urate lowering. Colchicine, a drug long used for gout, has been recently approved (for the first time ever) by the FDA, based on a new, safer dosing regimen. The recently appreciated centrality of IL-1β in acute gouty inflammation has prompted studies of agents blocking the IL-1β receptor or soluble IL-1β signaling (canakinumab, rilonacept, anakinra). Novel approaches to urate lowering have led to mechanism-based therapies such as urate synthesis inhibitors (febuxostat is already FDA approved and BCX4208 is in development), URAT-1 inhibitors promoting renal uric acid excretion (lesinurad), and recombinant uricase to directly catabolize urate (pegloticase). These new treatments do not obviate the need for lifestyle and dietary management, another area in which significant scientific and clinical progress has recently been made.
Efficient Near-Infrared Polymer Nanocrystal Light-Emitting Diodes (2002)

Conjugated polymers and indium arsenide-based nanocrystals were used to create near-infrared plastic light-emitting diodes. Emission was tunable from 1 to 1.3 micrometers--a range that effectively covers the short-wavelength telecommunications band--by means of the quantum confinement effects in the nanocrystals. The external efficiency value (photons out divided by electrons in) is approximately 0.5% (that is, >1% internal) and is mainly limited by device architecture. The near-infrared emission did not overlap the charge-induced absorption bands of the polymer.
Linearity Improvement of Power Amplifier using Modulation of Low Frequency IMD Signals (2006)

In this paper, a new predistortion linearizer for controlling the amplitude of low frequency intermodulation distortion signals is proposed. The low frequency intermodulation distortion (IMD) components are generated by harmonic generator. A vector modulator, modulate fundamental signal with low frequency IMD signals, generates predistortion IMD signals and controls amplitude and phase of them with modulation factors. As a result, this predistorter is suppressed IMD signals of power amplifier effectively. The predistortion linearizer has been manufactured to operate in cellular base-station transmitting band (869-894 MHz). The experimental results show that IMD/sub 3/ of power amplifier are improved more than 20dB for CW two-tone signals. Also, it's improved the adjacent channel power ratio (ACPR) more than 10dB for CDMA (IS-95) signals.
Yarrowia lipolytica Mutants Devoid of Pyruvate Carboxylase Activity Show an Unusual Growth Phenotype (2005)

We have cloned and characterized the gene PYC1, encoding the unique pyruvate carboxylase in the dimorphic yeast Yarrowia lipolytica. The protein putatively encoded by the cDNA has a length of 1,192 amino acids and shows around 70% identity with pyruvate carboxylases from other organisms. The corresponding genomic DNA possesses an intron of 269 bp located 133 bp downstream of the starting ATG. In the branch motif of the intron, the sequence CCCTAAC, not previously found at this place in spliceosomal introns of Y. lipolytica, was uncovered. Disruption of the PYC1 gene from Y. lipolytica did not abolish growth in glucose-ammonium medium, as is the case in other eukaryotic microorganisms. This unusual growth phenotype was due to an incomplete glucose repression of the function of the glyoxylate cycle, as shown by the lack of growth in that medium of double pyc1 icl1 mutants lacking both pyruvate carboxylase and isocitrate lyase activity. These mutants grew when glutamate, aspartate, or Casamino Acids were added to the glucose-ammonium medium. The cDNA from the Y. lipolytica PYC1 gene complemented the growth defect of a Saccharomyces cerevisiae pyc1 pyc2 mutant, but introduction of either the S. cerevisiae PYC1 or PYC2 gene into Y. lipolytica did not result in detectable pyruvate carboxylase activity or in growth on glucose-ammonium of a Y. lipolytica pyc1 icl1 double mutant.
Phosphorylation by Dyrk1A of Clathrin Coated Vesicle-Associated Proteins: Identification of the Substrate Proteins and the Effects of Phosphorylation (2012)

Dyrk1A phosphorylated multiple proteins in the clathrin-coated vesicle (CCV) preparations obtained from rat brains. Mass spectrometric analysis identified MAP1A, MAP2, AP180, and α- and β-adaptins as the phosphorylated proteins in the CCVs. Each protein was subsequently confirmed by [(32)P]-labeling and immunological methods. The Dyrk1A-mediated phosphorylation released the majority of MAP1A and MAP2 and enhanced the release of AP180 and adaptin subunits from the CCVs. Furthermore, Dyrk1A displaced adaptor proteins physically from CCVs in a kinase-concentration dependent manner. The clathrin heavy chain release rate, in contrast, was not affected by Dyrk1A. Surprisingly, the Dyrk1A-mediated phosphorylation of α- and β-adaptins led to dissociation of the AP2 complex, and released only β-adaptin from the CCVs. AP180 was phosphorylated by Dyrk1A also in the membrane-free fractions, but α- and β-adaptins were not. Dyrk1A was detected in the isolated CCVs and was co-localized with clathrin in neurons from mouse brain sections and from primary cultured rat hippocampus. Previously, we proposed that Dyrk1A inhibits the onset of clathrin-mediated endocytosis in neurons by phosphorylating dynamin 1, amphiphysin 1, and synaptojanin 1. Current results suggest that besides the inhibition, Dyrk1A promotes the uncoating process of endocytosed CCVs.
Introduction of oxygen into the alkyl chain of N-decyl-dNM decreases lipophilicity and results in increased retention of glucose residues on N-linked oligosaccharides (1994)

N-Alkylation of the alpha-glucosidase inhibitor 1-deoxynojirimycin (dNM) dramatically increases its inhibitory potency (Tan et al., J. Biol. Chem., 266, 14504-14510, 1991). However, the possibility of extending the alkyl chain to N-decyl-dNM is limited by an increase of detergent-like (amphiphilic) properties of long-chain alkylated dNM derivatives. Substitution of methylene groups in the N-decyl chain by oxygen reduced the amphiphilicity of N-decyl-dNM derivatives, while retaining their superior inhibitory properties. In intact HepG2 cells, the compound N-7-oxadecyl-dNM was found to result in the most pronounced retention of glucose residues on N-linked glycans. Permeabilization of the plasma membrane with the bacterial toxin Streptolysin O improves the inhibitory properties of the derivatives N-3,6,9-trioxadecyl-, N-7,10,13-trioxatetradecyl-, N-3-oxadecyl- and N-7-oxadecyl-dNM, but not those of dNM. These observations suggest differences in the mode of entry of the oxygen-substituted dNM derivatives in comparison with dNM. We observed that the dNM derivative N-3,6,9-trioxadecyl-dNM, devoid of inhibitory activity in intact cells, was inhibitory in Streptolysin O-permeabilized cells. Thus, the permeability barriers posed by plasma membrane and endoplasmic reticulum membrane are not equivalent. The use of a permeabilized cell system thus allows the elaboration of inhibitory principles for novel bioactive compounds where study of the isolated enzymes may not be possible, and where intact cells are not a suitable target due to permeability barriers.
Probiotics. Antistaphylococcal and antifibrinolytic activities of .omega.-amino- and .omega.-guanidinoalkanesulfonic acids (1975)

A series of omega-aminoalkanesulfonic acids (1-5) and omega-guanidinoalkanesulfonic acids (6-9) has been tested for antistaphylococcal and antifibrinolytic activities. Most of the omega-aminoalkanesulfonic acids and 6 produced better protection against Staphylococcus aureus infections in mice than gamma-aminobutyryl-L-histidine. Compound 4 was the best antistaphylococcal agent among the omega-aminoalkanesulfonic acids and compound 6 among the omega-guanidinoalkanesulfonic acids. Most of the omega-aminoalkanesulfonic acids have antifibrinolytic activity, while none of the omega-guanidinoalkanesulfonic acids has significant antifibrinolytic activity. Compound 4 possessed the highest antifibrinolytic activity which was equal to or greater than that of epsilon-aminohexanoic acid.
InAs channel heterostructure-field effect transistors with InAs/AlSb short-period superlattice barriers (1996)

We report on the implementation of InAs-channel heterostructure-field-effect transistors (HFETs) fabricated with InAs/AlSb short-period superlattice barriers. The InAs/AlSb superlattice barrier structure is advantageous for InAs/AlSb HFETs because of its improved chemical stability against oxidation when compared to pure AlSb, and its compatibility with silicon as an n-type dopant during growth by molecular beam epitaxy. The structures examined here consist of a 200-Å-wide InAs quantum well inserted between 25/25 Å InAs/AlSb superlattice barriers that provide a 0.5 eV conduction band discontinuity between the quantum well and the superlattice barrier. Fabricated HFET devices display complete channel modulation, confirming the field-effect operation at room temperature. In addition, we demonstrate the modulation doping of an InAs quantum well clad by silicon-doped InAs/AlSb superlattice barriers.
Rivastigmine, a New‐Generation Cholinesterase Inhibitor for the Treatment of Alzheimer's Disease (2000)

Rivastigmine is a cholinesterase inhibitor (ChEI) with a structural formula different from that of currently available ChEIs. Tacrine and donepezil are classified as short-acting or reversible agents since binding to acetylcholinesterase enzyme (AChE) is hydrolyzed within minutes. Rivastigmine is classified as an intermediate-acting or pseudo-irreversible agent due to its long inhibition on AChE of up to 10 hours. Preclinical biochemical studies indicated that rivastigmine has central nervous system selectivity over peripheral inhibition. It ameliorated memory impairment in rats with forebrain lesions. The drug is rapidly absorbed orally, with a bioavailability of 0.355 and low protein binding (40%). Its elimination half-life is less than 2 hours, and it is converted to an inactive metabolite at the site of action, bypassing hepatic metabolic pathways. Its disposition essentially is unaltered in patients with renal or hepatic impairment. It also has dose-dependent effects on AChE inhibition. In the two large multicenter clinical trials (total 1324 patients) that used a forced-dosage titration scheme, rivastigmine 6-12 mg/day was superior to placebo on three cognitive and functioning scales (p<0.001). Gastrointestinal symptoms are the most frequently reported adverse events. They occurred mostly during the dosage titration phase and decreased during the maintenance phase. Rivastigmine offers clinicians another therapeutic agent to treat Alzheimer's disease.
Pneumocystis carinii Infection in Transgenic B Cell-Deficient Mice (1996)

Pneumocystis carinii is an important cause of pneumonia in immunocompromised hosts. Both cellular and humoral immunity seem important in resistance to this pathogen, but the specific role of each component is poorly understood. An outbreak of P. carinii pneumonia in transgenic B cell-deficient mice (muMT) was studied. Over 4 months, >50% of 41 muMT/muMT mice maintained in a sterile environment died of pneumonia. Some mice had concurrent infection with Pasteurella pneumotropica. Homozygous muMT/muMT mice had no detectable serum immunoglobulins, while their heterozygous muMT/+ counterparts had normal levels of IgM, IgG, and IgA and did not develop pneumonia. The infection was controlled by treating the mice with trimethoprim-sulfamethoxazole, and the pathogen was eliminated by cesarean rederivation. These observations suggest an important role for B cells in the host defense against P. carinii.
Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling (2017)

The mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post-natal gland. Notably, the epithelium undergoes a large-scale shift in gene expression from a relatively homogeneous basal-like program in pre-puberty to distinct lineage-restricted programs in puberty. Interrogation of single-cell transcriptomes reveals different levels of diversity within the luminal and basal compartments, and identifies an early progenitor subset marked by CD55. Moreover, we uncover a luminal transit population and a rare mixed-lineage cluster amongst basal cells in the adult mammary gland. Together these findings point to a developmental hierarchy in which a basal-like gene expression program prevails in the early post-natal gland prior to the specification of distinct lineage signatures, and the presence of cellular intermediates that may serve as transit or lineage-primed cells.
Targeting transgene to the heart and liver with AAV9 by different promoters (2015)

Adeno-associated virus (AAV) has become one of the most promising gene transfer tools for gene therapy. This work aims to evaluate tropism, gene transfer efficiency and safety of AAV9 vectors produced with recombinant baculovirus (rBac)-based system. AAV9-CMV-GFP and AAV9-CBA-GFP were produced using a rBac system, 1 × 10(11) particles of each vectors were administered intravenously (i.v.) into mice and animals were killed at 1, 2, 3, 4, 5 and 8 weeks after administration. The GFP expression in different organs was analyzed by fluorescence imaging and Western blot. Viral genomic quantities were measured using qPCR. In vitro transduction efficiency of AAV9 vectors in primary cardiomyocytes and hepatocytes was determined by flow cytometry. Toxicity of AAV9 vectors was evaluated by determining certain cardiac and liver injury biomarkers and renal function test in vivo and TUNEL analysis in vitro. The data showed that AAV9 viral particles packaged by the rBac system were fully functional in vivo and in vitro. The CMV promoter predominantly induced higher cardiac GFP transgene expression and DNA copy numbers while the CBA promoter resulted in robust GFP expression and high vector DNA copy numbers in mouse liver, both in a time-dependent increased manner. Such distinct preferential effects were also observed in the heart and liver as early as 3 and 5 days after co-infection. Both the AAV9-CMV and AAV9-CBA viral packages did not induce heart, liver and renal damage and cell apoptosis. These results indicated that AAV9-CMV can efficiently and safely direct cardiac gene transfer, whereas AAV9-CBA is preferential for liver gene delivery.
Increased expression of osteopontin in the spinal cords of Lewis rats with experimental autoimmune neuritis (2004)

To investigate the pattern of expression of osteopontin (OPN) in tissues of the central nervous system (CNS) responding to peripheral immunological stimulation, the expression of OPN was studied in the spinal cord of rats with experimental autoimmune neuritis (EAN). In this model system, the sciatic nerves and spinal nerve roots are the target organs of EAN and the spinal cord is a remote organ that may be indirectly affected. OPN was constitutively expressed in some astrocytes adjacent to the pia mater and neurons in normal rats. In rats with EAN, OPN was increased in the same cells and in some inflammatory cells, including macrophages in the subarachnoid space. Expression of CD44, a receptor of OPN, was weak in normal spinal cord tissue and increased in the entire spinal cord parenchyma in rats with EAN, as well as in inflammatory cells. These findings suggest that inflammatory cells as well as reactive astrocytes are major sources of OPN and CD44 in the spinal cord of rats with EAN. Further study is needed to elucidate the functional role of OPN in the spinal cord affected by EAN.