gebhart/patrepeval huggingface dataset:
In Vivo Measurements of Neurotransmitters by Microdialysis Sampling (2006)

The brain contains a vast network of neurons that connect with each other at specialized junctions called synapses.A synapse consists of a presynaptic terminal (the "sending"neuron) and a postsynaptic bouton (the "receiving" neuron)that are separated by a gap of 5-50 nm (Figure 1). Chemicals released into this synaptic gap interact with receptors on the postsynaptic neuron. This leads to intracellular changes in the postsynaptic neuron-for example, an altered membrane potential or gene expression. The chemical signal is terminated by transporter proteins that transfer transmitter molecules across the membrane to the intracellular space (a process known as "reuptake")or enzymes that degrade the transmitter in the vicinity of the synapse (Figure 1). This classical view of neurotransmission might be considered point-to-point or"wired" communication because neurons communicate only with neurons to which they are specifically connected. In addition,neurotransmitters can activate receptors at more distant sites either by escaping the synapse or by being directly released into extrasynaptic space. This longer-range communication has been called "volume" transmission (1, S1; S references can be found in Supporting Information). All brain functions, from controlling movement to emotions, involve these two forms of chemical communication. Analytical chemistry has an important role to play in developing our understanding of the brain by providing tools for identification and measurement of the many chemicals involved in neurotransmission.
A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system. (1995)

We have studied the functional consequences of a mutation in the epithelial Na+ channel that causes a heritable form of salt-sensitive hypertension, Liddle disease. This mutation, identified in the original kindred described by Liddle, introduces a premature stop codon in the channel beta subunit, resulting in a deletion of almost all of the C terminus of the encoded protein. Coexpression of the mutant beta subunit with wild-type alpha and gamma subunits in Xenopus laevis oocytes resulted in an approximately 3-fold increase in the macroscopic amiloride-sensitive Na+ current (INa) compared with the wild-type channel. This change in INa reflected an increase in the overall channel activity characterized by a higher number of active channels in membrane patches. The truncation mutation in the beta subunit of epithelial Na+ channel did not alter the biophysical and pharmacological properties of the channel--including unitary conductance, ion selectivity, or sensitivity to amiloride block. These results provide direct physiological evidence that Liddle disease is related to constitutive channel hyperactivity in the cell membrane. Deletions of the C-terminal end of the beta and gamma subunits of rat epithelial Na+ channel were functionally equivalent in increasing INa, suggesting that the cytoplasmic domain of the gamma subunit might be another molecular target for mutations responsible for salt-sensitive forms of hypertension.
Virus complement evasion strategies (2003)

The immune system has a variety of tools at its disposal to combat virus infections. These can be subdivided roughly into two categories: 'first line defence', consisting of the non-specific, innate immune system, and 'adaptive immune response', acquired over time following virus infection or vaccination. During evolution, viruses have developed numerous, and often very ingenious, strategies to counteract efficient recognition of virions or virus-infected cells by both innate and adaptive immunity. This review will focus on the different strategies that viruses use to avoid recognition by one of the components of the immune system: the complement system. Complement evasion is of particular importance for viruses, since complement activation is a crucial component of innate immunity (alternative and mannan-binding lectin activation pathway) as well as of adaptive immunity (classical, antibody-dependent complement activation).
“Vanishing White Matter” and Ovarian Dysgenesis in an Infant with Cerebro-Oculo-Facio-Skeletal Phenotype (2002)

We describe a girl with intrauterine growth retardation, congenital cataracts, mild dysmorphic features and joint contractures. MRI performed at 1 week and 6 months, demonstrated postnatal cerebral and cerebellar atrophy and loss of white matter. The patient died at 10 months. Post-mortem examination revealed ovarian dysgenesis. There was normal development of neuronal and axonal structures, but lack of myelination in brainstem and cerebellum. Subcortical and deep white matter of the cerebral hemispheres were largely destroyed (cavitated), with preserved, but unmyelinated axons in other brain areas. These findings are compatible with a severe leukodystrophic process of pre- or perinatal onset. The exact pathogenesis is not known.
Concerted responses between the chitin-binding protein secreting Streptomyces olivaceoviridis and Aspergillus proliferans (2007)

Streptomycetes belong to the ecologically important bacterial population within soil, which is also inhabited by many fungi. The highly chitinolytic Streptomyces olivaceoviridis and the ascomycete Aspergillus proliferans were chosen as models to test for interactions among bacteria and fungi. In medium lacking a soluble carbon source, individually cultivated spores of the bacterium S. olivaceoviridis and the fungus A. proliferans do not germinate. However, as shown by viability tests, cultivation of a mixture of both spore types provokes successive events: (i) stimulation of the germination of S. olivaceoviridis spores, (ii) initiation of the outgrowth of some fungal spores to which the S. olivaceoviridis chitinase ChiO1 adheres, (iii) massive extension of viable networks of S. olivaceoviridis hyphae at the expense of fungal hyphae and (iv) balanced proliferation of closely interacting fungal and S. olivaceoviridis hyphae. The replacement of the S. olivaceoviridis wild-type strain by a chromosomal disruption mutant (DeltaC), lacking production of the extracellular chitin-binding protein CHB1 but still secreting the chitinase ChiO1, provokes (v) germination of each spore type, (vi) retarded development of both partners, followed by (vii) preferential proliferation of the fungus. Together with biochemical and immunomicroscopy studies, the data support the conclusion that CHB1 molecules aggregate to an extracellular matrix, maintaining a close contact, followed by several concerted responses of the bacterium and the fungus.
Expression of CD90 on keratinocyte stem/progenitor cells (2006)

These results indicated that CD90 is a useful marker for the detection of human KSC-enriched populations in cultured human keratinocytes.
The Ch14.18-GM-CSF fusion protein is effective at mediating antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro. (1999)

Granulocyte/macrophage-colony stimulating factor (GM-CSF) is very effective at enhancing antibody-dependent cellular cytotoxicity (ADCC) mediated by granulocytes and monocytes. Recently, a fusion protein consisting of GM-CSF and chimeric human/mouse anti-ganglioside G(D2) antibody Ch14.18 (Ch14.18-GM-CSF) has been generated to improve the effectiveness of immunotherapy by directing GM-CSF to the tumor microenvironment and prolonging its relatively short half-life. In this study, we examined the ability of this fusion protein to enhance the in vitro killing of G(D2)-expressing human neuroblastoma cells by granulocytes and mononuclear cells, as well as by complement. The Ch14.18-GM-CSF fusion protein was equally effective as the combination of equivalent amounts of free Ch14.18 and GM-CSF in mediating the killing of NMB7 neuroblastoma cells by granulocytes from seven of eight neuroblastoma patients. The fusion protein was also equally effective as the combination of Ch14.18 and GM-CSF in mediating ADCC by neuroblastoma patients' mononuclear cells. In addition, the fusion protein was as effective as Ch14.18 alone in directing complement-dependent cytotoxicity against NMB7 cells. Our results demonstrate that the biological activities expressed by ADCC and complement-dependent cytotoxicity of both monoclonal antibody Ch14.18 and GM-CSF are retained by the Ch14.18-GM-CSF fusion protein and lend further support for future clinical trials of this fusion protein in patients with neuroblastoma.
Adhesion molecules: a new target for immunoliposome‐mediated drug delivery (1995)

The anti-ICAM-1 monoclonal antibody F10.2 was conjugated to liposomes to target to cells expressing the cell adhesion molecule ICAM-1. We demonstrate that F10.2 immunoliposomes bind to human bronchial epithelial cells (BEAS-2B) and human umbilical vein endothelial cells (HUVEC) in a specific, dose- and time-dependent manner. It appears that the degree of ICAM-1 expression is the limiting factor in the degree of immunoliposome binding to the cells. These results are a first step in the strategy for specific drug delivery to target sites characterised by increased expression of adhesion molecules.
DNA REPAIR ENZYMES (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
A quantitative analysis of rate-limiting steps in the metastatic cascade using human-specific real-time polymerase chain reaction. (2002)

A quantitative assessment of rate-limiting steps in metastasis has always been challenging because of the difficulty of detecting small tumor cell populations. We have developed a highly sensitive assay for monitoring the metastatic dissemination of human tumor cells in the chick embryo and used this assay to investigate the relative efficacy of sequential stages in the metastatic cascade for two malignant human tumor cells lines, HEp3 and HT1080. This assay is based on the real-time PCR amplification of human alu sequences and exhibits a high sensitivity (25 cells/lung) with a large linear range (50-100,000 cell/lung). The assay is optimized for a high number of replicate in vivo assays (50-100 animals/assay) and can be applied in both experimental and spontaneous metastasis models. Using quantitative alu PCR, we determined that HEp3 spontaneously metastasizes very efficiently and rapidly, generating secondary growth in the lung exceeding 1-2 x 10(4) cells/lung in 7 days. In contrast, spontaneous HT1080 metastasis is 50-100-fold less efficient, resulting in only 200-400 cells/lung in 7 days. By taking advantage of the sensitivity and specificity of the real-time alu PCR assay we were also able to quantitatively assess multiple steps in metastasis including intravasation, arrest of tumor cells in secondary organs of the embryo, and the initial growth and expansion of the arrested tumor cells. A comparative analysis of HEp3 and HT1080 metastasis demonstrates that the relatively low-to-moderate metastatic rate of HT1080 is caused by two distinct deficiencies, an 8-10-fold lower rate of intravasation and a delayed onset of HT1080 growth expansion in the secondary organ. Thus, a very facile metastasis model system coupled with the sensitive, real-time PCR-based assay allows for the identification and quantification of rate-limiting steps in the metastatic cascade for select human tumor cell lines.
Isolation, analysis, and expression of two genes from Thermoanaerobacterium sp. strain JW/SL YS485: a beta-xylosidase and a novel acetyl xylan esterase with cephalosporin C deacetylase activity (1997)

The genes encoding acetyl xylan esterase 1 (axe1) and a beta-xylosidase (xylB) have been cloned and sequenced from Thermoanaerobacterium sp. strain JW/SL YS485. axe1 is located 22 nucleotides 3' of the xylB sequence. The identity of axe1 was confirmed by comparison of the deduced amino acid sequence to peptide sequence analysis data from purified acetyl xylan esterase 1. The xylB gene was identified by expression cloning and by sequence homology to known beta-xylosidases. Plasmids which independently expressed either acetyl xylan esterase 1 (pAct1BK) or beta-xylosidase (pXylo-1.1) were constructed in Escherichia coli. Plasmid pXylAct-1 contained both genes joined at a unique EcoRI site and expressed both activities. Substrate specificity, pH, and temperature optima were determined for partially purified recombinant acetyl xylan esterase 1 and for crude recombinant beta-xylosidase. Similarity searches showed that the axe1 and xylB genes were homologs of the ORF-1 and xynB genes, respectively, isolated from Thermoanaerobacterium saccharolyticum. Although the deduced sequence of the axe1 product had no significant amino acid sequence similarity to any reported acetyl xylan esterase sequence, it did have strong similarity to cephalosporin C deacetylase from Bacillus subtilis. Recombinant acetyl xylan esterase 1 was found to have thermostable deacetylase activity towards a number of acetylated substrates, including cephalosporin C and 7-aminocephalosporanic acid.
Delayed Gastric Emptying and Gastroesophageal Reflux: A Pathophysiologic Relationship (2001)

DGE seems to accentuate postprandial reflux by increasing the volume of refluxate per episode of reflux through an underlying incompetent lower esophageal sphincter.
Glycosaminoglycan-binding microbial proteins in tissue adhesion and invasion: key events in microbial pathogenicity (1999)

Glycosaminoglycans such as heparin, heparan sulphate and dermatan sulphate, are distributed widely in the human body. Several glycosaminoglycans form part of the extracellular matrix and heparan sulphate is expressed on all eukaryotic surfaces. The identification of specific binding to different glycosaminoglycan molecules by bacteria (e.g., Helicobacter pylori, Bordetella pertussis and Chlamydia trachomatis), viruses (e.g., herpes simplex and dengue virus), and protozoa (e.g., Plasmodium and Leishmania), is therefore of great interest. Expression of glycosaminoglycan-binding proteins depends on growth and culture conditions in bacteria, and differs in various phases of parasite development. Glycosaminoglycan-binding microbial proteins may mediate adhesion of microbes to eukaryotic cells, which may be a primary mechanism in mucosal infections, and are also involved in secondary effects such as adhesion to cerebral endothelia in cerebral malaria or to synovial membranes in arthritis caused by Borrelia burgdorferi. It has been suggested that they may enhance intracellular survival in macrophages. Microbial binding of heparin may interfere with heparin-dependent growth factors. Whether or not glycosaminoglycan-binding proteins mediate invasion of epithelial cells is a matter of controversy. Heparin and other glycosaminoglycans may have potential uses as therapeutic agents in microbial infections and could form part of future vaccines against such infections.
NFAT Induces Breast Cancer Cell Invasion by Promoting the Induction of Cyclooxygenase-2 (2006)

The NFAT (nuclear factor of activated T cells) family of transcription factors plays a fundamental role in the transcriptional regulation of the immune response. However, NFATs are ubiquitously expressed, and recent evidence points to their important functions in human epithelial cells and carcinomas. Specifically, NFAT has been shown to be active in human breast and colon carcinoma cells and to promote their invasion through Matrigel. The mechanisms by which NFAT promotes invasion have not been defined. To identify NFAT target genes that induce carcinoma invasion, we have established stable breast cancer cell lines that inducibly express transcriptionally active NFAT. Gene expression profiling by cDNA microarray of cells induced to express NFAT revealed up-regulation of cyclooxygenase-2 (COX-2). Increased NFAT expression and activity induced COX-2 expression as well as prostaglandin E2 synthesis. This induction was more prominent when NFAT was activated by phorbol 12-myristate 13-acetate and calcium ionophore ionomycin and was blocked by the NFAT antagonist cyclosporin A. Breast cancer cells with elevated COX-2 expression showed increased invasion through Matrigel, and this was reduced in cells treated with COX-2 inhibitors. Conversely, loss of NFAT1 protein expression using small interfering RNA led to a reduction in COX-2 transcription and reduced invasion. Similarly, Matrigel invasion was reduced in cells in which COX-2 expression was reduced using specific siRNA. These findings demonstrate that NFAT promotes breast cancer cell invasion through the induction of COX-2 and the synthesis of prostaglandins.
A phase II study of 6-diazo-5-oxo-L-norleucine (DON, NSC-7365) in advanced large bowel carcinoma (1983)

Rubin, Joseph M.D.; Sorensen, Scot M.D.; Schutt, Allan J. M.D.; van Hazel, Guy A. M.B.; O'Connell, Michael J. M.D.; Moertel, Charles G. M.D. Author Information
University-Based Water Research: Relevant to Society? (2002)

In recent years the complexity of a number of water management issues have begun to confound water managers as well as the citizens who pay for water management. Flood and drought planning and management, creation of a Total Maximum Daily Load (TMDL) list per Section 303(d) of the Clean Water Act, and describing the quality of the nation’s drinking water are examples of water issues demanding more science, data and understanding than seems available. The demand for “sound science ” to support better water management decision-making is often heard when conflicts develop around particularly difficult water management issues. How is “sound science ” in support of water management procured? The university community, as well as the broader scientific community, uses the concept of “peer review ” to judge the “soundness ” of science and research. Why is there a call for sound science today when it has been a part of water research for many years? More specifically, does peer review science insure that science is of interest only to “peers”? Is peer reviewed science performed by mission oriented agencies (e.g. EPA, USDA, &amp;amp; USGS) of interest only to employees of the agency or their disciplinary missions? Is the scientific curiosity of university faculty of interest to anyone other than the curious faculty member? These are not easy questions to answer, especially for the
Measuring Monetary Policy and Pass-Through in Chile (2002)

First, this paper reviews the most important literature based on money VAR, which explains monetarytransmission mechanisms and pass-through from depreciation to inflation in Chile and other countries. Second, it estimates three structural VAR models with short-run restrictions and one VEC with long-run restrictions. The results indicate that monetary-transmission has become less powerful in the last years than in the period 1986-1997 and that the low pass-through depends on economic activity, inflation and the inflation target.
A Simple and Sensitive Method for in Vitro Quantitation of Abasic Sites in DNA (1999)

A novel method for the quantitation of abasic sites (AP sites) in DNA is described. As abasic sites can be generated by controlled thermal treatment of base-modified DNA, this method can be used for estimation of the extent of DNA damage resulting from exposure to genotoxic agents. The method involves use of probe molecules 1 and 2 that contain a fluorescent label linked to an aminooxy group which reacts specifically with the aldehydic function of the ring-opened form of abasic sites. The two fluorescent probes 1 and 2 were found to react with 2-deoxyribose, a model substrate, at the optimum of pH 4.0. As spontaneous depurination occurs at low pH, the reactions with abasic DNA were carried out at neutral pH with an excess concentration of the probes. Studies with alkylated, depurinated calf thymus DNA showed that the method is selective and quantitative. Good correlations were found between the level of 7-methylguanine (7-MeGua), generated in vitro in DNA by the methylating agent dimethyl sulfate, and the amount of AP sites as determined by the method presented here. In addition, similar correlations were found when the assay was used to detect abasic sites in DNA isolated from rats treated with carcinogenic alkylating agents. In each case, the level of abasic sites, as expected, is slightly higher than the level of 7-MeGua which is known to represent about 70% of the total modifications of DNA following exposure to the methylating agent. This method may be useful not only in experimental settings but also in studies of DNA damage in humans resulting from chemotherapy or exposure to environmental agents.
Metabotropic Glutamate Receptor-Mediated Hippocampal Phosphoinositide Turnover Is Blunted in Spatial Learning-Impaired Aged Rats (1999)

Maximal phosphoinositide (PI) turnover was examined in the hippocampus of young and aged Long-Evans rats that were behaviorally characterized for spatial learning in the Morris water maze. The type 1 metabotropic glutamate receptor (mGluR) agonist 1S,3R ACPD was used to stimulate PI turnover and to determine the E(MAX) for each rat. Protein levels in hippocampus for type 1 mGluRs, Galphaq11, and phospholipase Cbeta-1 (PLCbeta-1) were also measured by quantitative Western blotting. The results show that PI turnover mediated by the mGluRs was blunted in the aged rats. The magnitude of the decrement in PI turnover was also significantly correlated with age-related spatial memory decline. The decrease in mGluR-mediated PI turnover occurred without changes in the protein level of either the mGluRs or the G-protein coupled to those receptors, Galphaq11. A significant decrease in the immunoreactivity of PLCbeta-1, however, was observed in the hippocampus of aged rats; PLCbeta-1 immunoreactivity was significantly correlated with spatial learning only when the young and aged rats were considered together. The decrement in mGluR-mediated signal transduction in the hippocampus that is related to cognitive impairment in aging may be attributable, at least in part, to a deficiency in the enzyme PLCbeta-1. That deficiency may also contribute to a blunted response in muscarinic stimulation of hippocampal PI turnover that we previously found in this same study population. An age-related alteration in this signal transduction system may provide a functional basis for cognitive decline independent of any loss of neurons in the hippocampus.
Induction of transformation and DNA synthesis after microinjection of raf proteins. (1990)

Full-length and N-terminal deletion mutants of human c-raf-1 cDNA were cloned into Escherichia coli expression plasmids. Bacterially expressed c-raf proteins were purified by anion-exchange, gel filtration, and affinity chromatography. Microinjection of mutant c-raf proteins into G0-arrested NIH 3T3 cells induced DNA synthesis and morphological transformation, whereas microinjection of full-length c-raf had no effect. The amino terminus of the raf protein has an important negative regulatory influence; alteration of this region resulted in increased kinase activity and oncogenicity.
Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice (2000)

In Huntington's disease (HD), mutation of huntingtin causes selective neurodegeneration of dopaminoceptive striatal medium spiny neurons. Transgenic HD model mice that express a portion of the disease-causing form of human huntingtin develop a behavioral phenotype that suggests dysfunction of dopaminergic neurotransmission. Here we show that presymtomatic mice have severe deficiencies in dopamine signaling in the striatum. These include selective reductions in total levels of dopamine- and cAMP-regulated phosphoprotein, M(r) 32 kDA (DARPP-32) and other dopamine-regulated phosphoprotein markers of medium spiny neurons. HD mice also show defects in dopamine-regulated ion channels and in the D(1) dopamine/DARPP-32 signaling cascade. These presymptomatic defects may contribute to HD pathology.