gebhart/patrepeval huggingface dataset:
Participation of Survivin in mitotic and apoptotic activities of normal and tumor‐derived cells* (2001)

Survivin is a member of the inhibitor of apoptosis (IAP) gene family, containing a single baculovirus IAP repeat (BIR) and no RING finger, that is expressed in many human cancers. Although it has been proposed to be involved in mitotic and cytokinetic processes, its functional subcellular distribution in the cytoplasm and nucleus, and its binding to centrosomes, spindle fibers, and centromeres in relation to these processes, is not fully resolved. We have analyzed the localization of Survivin in normal (Detroit 551, IMR-90) and tumor-derived (HeLa, Saos-2) cell lines, and found that it does colocalize with centrosomes in the cytoplasm during interphase, then moves to centromeres during mitosis, and finally localizes to the midbody spindle fibers during telophase. However, Taxol, a popular microtubule stabilizing agent that is frequently used in the study of these processes, severely disrupted the localization of Survivin. Taxol treatment of cells promoted extensive relocalization of Survivin with alpha-tubulin on microtubules during either interphase or mitosis. Survivin antisense oligonucleotide markedly sensitized HeLa cells to cell death induced by agents acting at the level of cell surface receptor (Fas pathway) or at the level of mitochondria (etoposide). HeLa cell death induced by Survivin antisense oligonucleotide could be partially complemented by Deterin, the Drosophila homolog of Survivin (Jones et al. [2000] J. Biol. Chem. 275:22157-22166). Reciprocally, a chimera of the Deterin BIR domain and Survivin C-terminus could rescue Drosophila Kc cells from death induced by transfection of a human caspase-7-expressing plasmid. These results indicate common components of Survivin and Deterin antiapoptotic action in the vertebrate and invertebrate phyla.
Haploinsufficiency and reduced expression of genes localized to the 8p chromosomal region in human prostate tumors (2003)

Cytogenetic and molecular studies have suggested that deletion or rearrangement of sequences that map to the short arm of chromosome 8 may be permissive for tumorigenesis in several organ systems, and in human prostate tumors in particular. In this study, we hypothesized that genes deleted for one copy and localized to the 8p chromosomal region may be transcriptionally down-regulated or ablated in affected human prostate tumor tissues. To test this hypothesis, we used cDNA microarray analysis to determine the transcriptional profiles for 259 transcribed sequences mapping to the 8p chromosomal region for seven human prostate tumor xenografts, completely characterized for numerical and structural alterations on chromosome 8, and five normal human prostate tissues. These experiments identified 33 genes differentially expressed between normal and malignant prostate tissues, the majority of which (28/33, 85%) were transcriptionally down-regulated in malignant compared to normal human prostate tissues. These findings, that haploinsufficiency and transcriptional down-regulation for genes mapping to 8p are largely coincident in human prostate tumors, should provide a powerful tool for the identification of tumor-suppressor genes associated with human prostate cancer initiation and progression.
The use of peptides to reconstruct conformational determinants; a brief review. (1991)

In many biological processes, defined regions of proteins are involved in selective recognition. These regions can often be mimicked with peptides and are the main targets for vaccine and drug development. The authors review the use of peptides, to define and ultimately mimic defined protein regions of interest. Especially the role of the Pepscan method is emphasized. This method has been proven to be a useful and fast tool in defining protein regions of interest. It is based on the simultaneously synthesis of multiple peptides coupled to solid supports. Hundreds of peptides can be produced and tested in a relatively short period of time. With the construction of random peptide libraries in recombinant DNA systems, it is now even possible to screen for peptidic determinants without the requirement of preliminary knowledge of primary structure. Having this information, the affinity of peptides can be further enhanced with the Pepscan approach. The power of this approach will be illustrated with results from studies on the development of synthetic vaccines and hormone analogues.
S‐Adenosylmethionine: a control switch that regulates liver function (2002)

Genome sequence analysis reveals that all organisms synthesize S-adenosylmethionine (AdoMet) and that a large fraction of all genes is AdoMet-dependent methyltransferases. AdoMet-dependent methylation has been shown to be central to many biological processes. Up to 85% of all methylation reactions and as much as 48% of methionine metabolism occur in the liver, which indicates the crucial importance of this organ in the regulation of blood methionine. Of the two mammalian genes (MAT1A, MAT2A) that encode methionine adenosyltransferase (MAT, the enzyme that makes AdoMet), MAT1A is specifically expressed in adult liver. It now appears that growth factors, cytokines, and hormones regulate liver MAT mRNA levels and enzyme activity and that AdoMet should not be viewed only as an intermediate metabolite in methionine catabolism, but also as an intracellular control switch that regulates essential hepatic functions such as regeneration, differentiation, and the sensitivity of this organ to injury. The aim of this review is to integrate these recent findings linking AdoMet with liver growth, differentiation, and injury into a comprehensive model. With the availability of AdoMet as a nutritional supplement and evidence of its beneficial role in various liver diseases, this review offers insight into its mechanism of action.
The selective neuronal NO synthase inhibitor 7-nitro-indazole blocks both long-term potentiation and depotentiation of field EPSPs in rat hippocampal CA1 in vivo (1996)

The membrane-permeant gas NO is a putative intercellular messenger that has been proposed on the basis of previous in vitro studies to be involved in synaptic plasticity, especially the induction of long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus and cortex. In the present study, the role of NO in synaptic plasticity has been investigated in vivo. In particular, the action of the novel and selective neuronal NO synthase (nNOS) inhibitor 7-nitro-indazole (7-NI) has been investigated on the induction of LTP and depotentiation (DP) of field EPSPs in CA1 of the hippocampus in vivo. Unlike previously studied nonselective NOS inhibitors, 7-NI does not increase arterial blood pressure. In vehicle-injected rats, high-frequency stimulation consisting of a series of trains at 200 Hz induced LTP. However, LTP induction was strongly inhibited in 7-NI (30 mg/kg, i.p.)-treated animals. The inhibitory effect of 7-NI on the induction of LTP was prevented by pretreatment with L-arginine, the substrate amino acid used by NOS. In control animals, low-frequency stimulation consisting of 900 stimuli at 10 Hz induced DP of previously established LTP, whereas in 7-HI-treated animals only a short-term depression was induced. This effect of 7-NI also was prevented by D-arginine. The LTP and DP induced in control animals in this study were NMDA receptor-dependent, the NMDA receptor antagonist 3-(R,S)-2-carboxypiperazin-4-yl-propyl-1- phosphonic acid inhibiting the induction of both forms of synaptic plasticity. The present experiments are the first to demonstrate that an NOS inhibitor blocks the induction of the synaptic component of LTP and DP in vivo and, therefore, these results strengthen evidence that the production of NO is necessary for the induction of LTP and DP.
Distribution, blood transport, and degradation of antidiuretic hormone in man. (1976)

The distribution, blood transport, and metabolic clearance of physiological concentrations of antidiuretic hormone were studied in 10 hydrated normal subjects with radioiodinated arginine vasopressin (125I-AVP). At 37 degrees C no binding of 125I-AVP to plasma proteins could be demonstrated, but some metabolites were associated with plasma proteins. 125I-AVP was rapidly distributed into a space approximating the extracellular fluid volume. Metabolic breakdown products became demonstrable within minutes after injection. The mean metabolic clearance rate of 125I-AVP was 4.1 ml/min/kg and the mean plasma half-life 24.1 min. Renal clearance had a mean value of 80 ml/min and accounted for 27% of the total metabolic clearance. It is concluded that in man antidiuretic hormone circulates as a free (non-protein bound) peptide, diffuses readily into the extracellular fluid space, and is metabolized within minutes. A plasma half-life of 24 min is consistent with the duration of antidiuresis after hormone administration or release.
Inhibitory effects of decoy-ODN targeting activated STAT3 on human glioma growth in vivo. (2009)

The present study suggested that decoy-ODN provide an effective therapeutic approach to treat glioma in vivo.
Scaled 1T-bulk devices built with CMOS 90nm technology for low-cost edram applications (2005)

A one transistor DRAM cell realized on bulk substrate (lT-Bulk) with CMOS 90nm platform is presented for the first time. The device fabrication is fully compatible with logic process integration and includes only few additional steps, thus making this IT cell very attractive for low-cost embedded memories. Very scaled devices were fabricated with a gate length down to 80nm and several gate oxide thicknesses: their performances in terms of memory effect amplitude, retention time and disturb margins are very promising for future high density eDRAM.
Relative Solvent Accessible Surface Area Predicts Protein Conformational Changes upon Binding (2011)

Protein interactions are often accompanied by significant changes in conformation. We have analyzed the relationships between protein structures and the conformational changes they undergo upon binding. Based upon this, we introduce a simple measure, the relative solvent accessible surface area, which can be used to predict the magnitude of binding-induced conformational changes from the structures of either monomeric proteins or bound subunits. Applying this to a large set of protein complexes suggests that large conformational changes upon binding are common. In addition, we observe considerable enrichment of intrinsically disordered sequences in proteins predicted to undergo large conformational changes. Finally, we demonstrate that the relative solvent accessible surface area of monomeric proteins can be used as a simple proxy for protein flexibility. This reveals a powerful connection between the flexibility of unbound proteins and their binding-induced conformational changes, consistent with the conformational selection model of molecular recognition.
Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening (2002)

High density cDNA microarray screening was used to determine changes in gene expression occurring during the transition between the early luteal (prereceptive) and mid-luteal (receptive) phases in human endometrium. Of approximately 12,000 genes profiled, 693 (5.8%) displayed >2-fold differences in relative levels of expression between these stages. Of these, 370 genes (3.1%) displayed decreases ranging from 2- to >100-fold while 323 genes (2.7%) displayed increases ranging from 2- to >45-fold. Many genes correspond to mRNAs encoding proteins previously shown to change in a similar manner between the proliferative and mid-luteal phases, serving as one validation of the microarray screening results. In addition, novel genes were identified. Genes encoding cell surface receptors, adhesion and extracellular matrix proteins and growth factors accounted for 20% of the changes. Several genes were studied further by Northern blot analyses. These results confirmed that claudin-4/Clostridium perfringens enterotoxin (CPE) receptor and osteopontin (OPN) mRNA increased approximately 4- and 12-fold respectively, while betaig-H3 (BIGH3) decreased >80% during the early to mid-luteal transition. Immunostaining also revealed strong specific staining for claudin-4/CPE, EP(1) and prostaglandin receptor in epithelia, and leukotriene B4 receptor in both epithelia and stroma, at the mid-luteal stage. Collectively, these studies identify multiple new candidate markers that may be used to predict the receptive phase in humans. Some of these gene products, e.g. OPN, may play direct roles in embryo-uterine interactions during the implantation process.
Linear-After-The-Exponential (LATE)–PCR: An advanced method of asymmetric PCR and its uses in quantitative real-time analysis (2004)

Conventional asymmetric PCR is inefficient and difficult to optimize because limiting the concentration of one primer lowers its melting temperature below the reaction annealing temperature. Linear-After-The-Exponential (LATE)-PCR describes a new paradigm for primer design that renders assays as efficient as symmetric PCR assays, regardless of primer ratio. LATE-PCR generates single-stranded products with predictable kinetics for many cycles beyond the exponential phase. LATE-PCR also introduces new probe design criteria that uncouple hybridization probe detection from primer annealing and extension, increase probe reliability, improve allele discrimination, and increase signal strength by 80-250% relative to symmetric PCR. These improvements in PCR are particularly useful for real-time quantitative analysis of target numbers in small samples. LATE-PCR is adaptable to high throughput applications in fields such as clinical diagnostics, biodefense, forensics, and DNA sequencing. We showcase LATE-PCR via amplification of the cystic fibrosis CFDelta508 allele and the Tay-Sachs disease TSD 1278 allele from single heterozygous cells.
Transgenic expression of IFN-alpha in the central nervous system of mice protects against lethal neurotropic viral infection but induces inflammation and neurodegeneration. (1998)

Type I IFNs, which include IFN-alpha, appear to have complex and broad-ranging actions in the central nervous system (CNS) that may result in protection or injury. To better understand these issues, we generated transgenic mice that produce IFN-alpha1 chronically from astrocytes. These glial fibrillary acidic protein-IFN-alpha transgenic mice developed a progressive inflammatory encephalopathy, with marked calcium mineralization, meninoencephalitis, gliosis, and neurodegeneration. Many features of this murine encephalopathy resembled those found in certain human encephalopathies of unknown etiology; these diseases, exemplified by Aicardi-Goutières syndrome and some viral encephalopathies, show increased intrathecal production of IFN-alpha. Our data suggest that IFN-alpha overproduction may be the primary factor initiating these human diseases. Following intracerebral infection with lymphocytic choriomeningitis virus, glial fibrillary acidic protein-IFN-alpha mice had significantly increased survival rates associated with markedly reduced virus titers and immune pathology in the brain but normal peripheral CTL responses. Therefore, the production of IFN-alpha in the CNS can be a two-edged sword that on the one hand confers protection against a lethal viral infection but on the other causes significant injury to the brain. These transgenic mice provide a novel animal model in which to further evaluate the mechanisms that underlie the diverse actions of type I IFNs in the intact CNS.
Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants (2006)

Neurotrophic factors are agents with a promising ability to retard progression of neurodegenerative diseases and are effective in slowing photoreceptor degeneration in animal models of retinitis pigmentosa. Here we report a human clinical trial of a neurotrophic factor for retinal neurodegeneration. In this Phase I safety trial, human ciliary neurotrophic factor (CNTF) was delivered by cells transfected with the human CNTF gene and sequestered within capsules that were surgically implanted into the vitreous of the eye. The outer membrane of the encapsulated cell implant is semipermeable to allow CNTF to reach the retina. Ten participants received CNTF implants in one eye. When the implants were removed after 6 months, they contained viable cells with minimal cell loss and gave CNTF output at levels previously shown to be therapeutic for retinal degeneration in rcd1 dogs. Although the trial was not powered to form a judgment as to clinical efficacy, of seven eyes for which visual acuity could be tracked by conventional reading charts, three eyes reached and maintained improved acuities of 10-15 letters, equivalent to two- to three-line improvement on standard Snellen acuity charts. A surgically related choroidal detachment in one eye resulted in a transient acuity decrease that resolved with conservative management. This Phase I trial indicated that CNTF is safe for the human retina even with severely compromised photoreceptors. The approach to delivering therapeutic proteins to degenerating retinas using encapsulated cell implants may have application beyond disease caused by genetic mutations.
Catalysis of superoxide dismutation by iron-ethylenediaminetetraacetic acid complexes. Mechanism of the reaction and evidence for the direct formation of an iron(III)-ethylenediaminetetraacetic acid peroxo complex from the reaction of superoxide with iron(II)-ethylenediaminetetraacetic acid (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCatalysis of superoxide dismutation by iron-ethylenediaminetetraacetic acid complexes. Mechanism of the reaction and evidence for the direct formation of an iron(III)-ethylenediaminetetraacetic acid peroxo complex from the reaction of superoxide with iron(II)-ethylenediaminetetraacetic acidGregory J. McClune, James A. Fee, Gary A. McCluskey, and John T. GrovesCite this: J. Am. Chem. Soc. 1977, 99, 15, 5220–5222Publication Date (Print):June 1, 1977Publication History Published online1 May 2002Published inissue 1 June 1977https://doi.org/10.1021/ja00457a074RIGHTS & PERMISSIONSArticle Views190Altmetric-Citations66LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (398 KB) Get e-Alerts Get e-Alerts
Olfaction: Transient expression of a putative odorant receptor in the avian notochord (1997)

In vertebrates, odors are thought to be detected by a multigene family encoding several hundreds of seven-transmembrane-domain G-protein-coupled receptors found in fish, rat, mouse, dog, and human. Recently, the putative odorant receptor (OR) gene family in the chicken has been characterized. Twelve members have been isolated and subdivided into six subfamilies. Herein, we have further characterized the chicken olfactory receptor subfamily 7 (COR7) composed of two highly related genes (named COR7a and COR7b) which are 98.5% identical. By in situ hybridization experiments, both COR7a and COR7b transcripts were detected in the olfactory epithelium from embryonic day 6 (E6) to the new born stage. Within the olfactory epithelium, the spatial distribution of COR7a and COR7b labeled cells was random. We also observed that every individual positive cell did not coexpress the COR7a and COR7b genes. Interestingly, the COR7b gene was found to be transiently expressed in the notochord from E2 to E6, whereas COR7a or any of the other known members of the COR gene family were not detected in this mesodermal tissue. These data suggest that, in addition to its potential role as an OR in the olfactory system, COR7b may also have a function in the notochord that is essential for the dorsoventral organization of the neural tube and of the somitic mesoderm. We also discuss the possible role(s) of a putative OR present in both the notochord and the sensory olfactory epithelium.
Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. (1996)

Oncostatin M (OSM) is a member of the interleukin-6 (IL6)-related cytokine subfamily that includes IL6, IL11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor and cardiotrophin-1. While human OSM has been characterized and the bovine OSM gene was recently cloned, the murine counterpart had not been identified. Here we describe molecular cloning of murine OSM as an immediate early gene induced by a subset of cytokines including IL2, IL3 and erythropoietin (EPO) in myeloid and lymphoid cell lines. The induction kinetics of OSM are rapid and transient, reaching a maximal level within 30-60 min and decreasing thereafter. Induction of OSM depends on the signals generated by the membrane-proximal region of the EPO receptor as well as that of the beta chain of the IL3/GM-CSF receptor, which activate JAK2 and STAT5. About 100 bases upstream of the transcription initiation site of the OSM gene contains a possible STAT5 binding site which is essential for IL2, IL3 and EPO-dependent promoter activity of the OSM gene. Expression of STAT5 and the EPO receptor in COS cells conferred EPO-dependent activation of the OSM promoter. Moreover, the mutant IL2 receptor lacking the ability to activate STAT5 induced c-myc but failed to induce OSM. Thus OSM is one of the common targets of a subset of cytokines that activate STAT5. The murine OSM gene is located near to the LIF gene, expressed at high levels in bone marrow and possesses similar biological activity to human OSM. Identification of murine OSM as a cytokine-inducible immediate early gene provides a new insight into the physiological function of this unique cytokine.
Compromised Function of Regulatory T Cells in Rheumatoid Arthritis and Reversal by Anti-TNFα Therapy (2004)

Regulatory T cells have been clearly implicated in the control of disease in murine models of autoimmunity. The paucity of data regarding the role of these lymphocytes in human autoimmune disease has prompted us to examine their function in patients with rheumatoid arthritis (RA). Regulatory (CD4(+)CD25(+)) T cells isolated from patients with active RA displayed an anergic phenotype upon stimulation with anti-CD3 and anti-CD28 antibodies, and suppressed the proliferation of effector T cells in vitro. However, they were unable to suppress proinflammatory cytokine secretion from activated T cells and monocytes, or to convey a suppressive phenotype to effector CD4(+)CD25(-) T cells. Treatment with antitumor necrosis factor alpha (TNFalpha; Infliximab) restored the capacity of regulatory T cells to inhibit cytokine production and to convey a suppressive phenotype to "conventional" T cells. Furthermore, anti-TNFalpha treatment led to a significant rise in the number of peripheral blood regulatory T cells in RA patients responding to this treatment, which correlated with a reduction in C reactive protein. These data are the first to demonstrate that regulatory T cells are functionally compromised in RA, and indicate that modulation of regulatory T cells by anti-TNFalpha therapy may be a further mechanism by which this disease is ameliorated.