gebhart/patrepeval huggingface dataset:
Signal Transducer and Activator of Transcription 3 Activation Promotes Invasive Growth of Colon Carcinomas through Matrix Metal loproteinase Induction (2007)

Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in colorectal carcinomas (CRCs). Here, we define the relationship between STAT3 function and the malignant properties of colon carcinoma cells. Elevated activation of STAT3 enhances invasive growth of the CRC cell lines. To address mechanisms through which STAT3 influences invasiveness, the protease mRNA expression pattern of CRC biopsies was analyzed and correlated with the STAT3 activity status. These studies revealed a striking coincidence of STAT3 activation and strong expression of matrix metalloproteinases MMP-1, -3, -7, and -9. Immunohistological examination of CRC tumor specimens showed a clear colocalization of MMP-1 and activated STAT3. Experimentally induced STAT3 activity in CRC cell lines enhanced both the level of MMP-1 mRNA and secreted MMP-1 enzymatic activity. A direct connection of STAT3 activity and transcription from the MMP-1 promoter was shown by reporter gene experiments. Moreover, high-affinity binding of STAT3 to STAT recognition elements in both the MMP-1 and MMP-3 promoter was demonstrated. Xenograft tumors arising from implantation of CRC cells into nude mice showed simultaneous appearance and colocalization of p-Y-STAT3 and MMP-1 expression. Our results link aberrant activity of STAT3 in CRC to malignant tumor progression through upregulated expression of MMPs.
EpCAM and gpA33 are markers of Barrett’s metaplasia (2006)

EpCAM protein and gpA33 mRNA expressions are specific and sensitive markers of BM.
Dynamic Range Reduction Inspired by Photoreceptor Physiology (2004)

A common task in computer graphics is the mapping of digital high dynamic range images to low dynamic range display devices such as monitors and printers. This task is similar to the adaptation processes which occur in the human visual system. Physiological evidence suggests that adaptation already occurs in the photoreceptors, leading to a straightforward model that can be easily adapted for tone reproduction. The result is a fast and practical algorithm for general use with intuitive user parameters that control intensity, contrast, and level of chromatic adaptation, respectively.
Antimetastatic effect of amiloride in an animal tumour model. (1989)

The diuretic Amiloride competitively inhibits the catalytic activity of the urokinase-type plasminogen activator on plasminogen in vitro. This effect was tested on a rat adenocarcinoma model and its invasive potential in the host lung. While the inhibitory effect on intact cell cultures of the tumour was slight, continuous exposure of tumour-injected animals to the drug completely prevented the formation of lung metastasis.
Blood, Brain, and Cerebrospinal Fluid Concentrations of Several Antibiotics in Rabbits with Intact and Inflamed Meninges (1977)

Because cerebrospinal fluid (CSF) antibiotic levels fail to predict either clinical success or relapse in the treatment of bacterial meningitis, we examined simultaneous antibiotic concentrations in the blood, brain, and CSF of control rabbits and of animals with experimental pneumococcal meningitis. Cefamandole pharmacokinetics were analyzed in detail and compared with those of cephalothin, ampicillin, penicillin G, and tobramycin. After 4 h of continuous intravenous infusion, cefamandole reached concentrations in both brain and CSF in excess of the minimal bactericidal concentration for the test organism and compared favorably with ampicillin and penicillin in achieving bacteriological cure. Cephalothin levels in the central nervous system remained undetectable in both control and infected animals during this time. Tobramycin concentrations were measurable in the CSF, but not in brain tissue in association with an inflammatory stimulus.
No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis (2012)

The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.
Transient immunosuppression permits successful repetitive intravenous administration of an adenovirus vector. (1996)

The in vivo administration of adenovirus vectors frequently elicits a neutralizing antibody response which eliminates or substantially reduces the efficacy of subsequent treatments. Methods to overcome this significant barrier to repeat delivery will be required for the application of adenovirus-based gene therapy in the treatment of chronic disease. We have evaluated the relationship between the initial vector dose and the effectiveness of a second vector administration. C57BL/6 mice injected intravenously with up to 10(7) p.f.u. of a lacZ adenovirus vector, Av1lacZ4, expressed significant levels of human factor IX when injected with 2 x 10(8) p.f.u. of the factor IX vector, Av1H9F, 5 weeks later. An initial dose of 10(8) p.f.u. of Av1lacZ4 completely prevented expression of factor IX following the second administration due to the generation of neutralizing antibody. However, transient immunosuppression with deoxyspergualin (DSG) or cyclophosphamide at the time of initial exposure to 10(8) p.f.u. of Av1lacZ4 prevented the formation of anti-adenovirus neutralizing antibody and permitted an effective second administration of a factor IX vector. Furthermore, transient immunosuppression with cyclophosphamide concomitant with delivery of the factor IX vector enabled an effective administration of a third vector encoding human factor VIII. This approach, together with strategies to prolong the persistence of adenoviral vector expression, should permit long-term therapy with adenovirus-based vectors.
Flk-1, a Receptor for Vascular Endothelial Growth Factor (VEGF), Is Expressed by Retinal Progenitor Cells (1996)

Throughout development of the vertebrate retina, progenitor cells are multipotential, producing a variety of distinctive cell types. Little is known of the molecular mechanisms directing the determination of cell fate. We have examined retinal progenitor cells for expression of receptor tyrosine kinases in an attempt to define receptors that could allow a progenitor to respond to its environment. We found that the receptor tyrosine kinase Flk-1, previously shown to be expressed in endothelial cells, is also expressed in neural progenitor cells of the mouse retina. Flk-1 RNA expression in the retinal progenitors commences with the onset of neuronal differentiation and persists throughout retinal neurogenesis. Flk-1 RNA and protein levels in the retina vary temporally during development, as shown by in situ hybridization and Western blot analysis. Patterns of beta-galactosidase expression in mice containing the lacZ gene in place of the Flk-1 gene are consistent with Flk-1 being expressed in retinal progenitors. In addition, we show that the ligand of Flk-1, vascular endothelial growth factor (VEGF), is expressed in the developing retina by differentiated cells and that a chimeric ligand of VEGF fused to alkaline phosphatase binds to proliferating retinal progenitors. Furthermore, the neural retina-derived Flk-1 protein kinase is activated by VEGF in vitro. Thus, the Flk-1 receptor protein kinase is expressed on the surface of neural progenitors in mouse retina and may play a critical role in neurogenesis as well as in vasculogenesis.
Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes (1983)

Herpes simplex virus (HSV) genes form three groups, alpha, beta, and gamma, whose synthesis is coordinately regulated and sequentially ordered in a cascade fashion. Earlier studies by Post et al. (Cell 24:555-565, 1981) have shown that chimeric genes constructed by fusion of 5' noncoding leader and upstream sequences of alpha genes to the 5' noncoding leader and structural sequences of the viral thymidine kinase (TK), a beta gene, are regulated as alpha genes upon recombination into the viral genome. In cells converted from TK- to TK+ phenotype, these chimeric genes are induced by infection with homologous TK- virus. The induction of the resident chimeric gene does not require viral protein synthesis and is independent of the presence of functional alpha gene 4 product required for the expression of beta genes. In this paper, we report on the properties of the alpha-TK gene chimera resident in converted TK+ murine (L316) and human (I316) cells. Our results were as follows. (i) The pattern of induction of L316 cells exposed to 0.1, 1.0, and 10 PFU per cell suggested that exposure to competent virus is required for induction and that in untreated preparations this virus corresponds to infectious virus. (ii) UV light-irradiated virus was just as effective as untreated virus in inducing alpha-TK chimeras. (iii) HSV-1(HFEM)tsB7 induced the alpha-TK gene chimeras at the nonpermissive (39 degrees C) temperature; at 39 degrees C the parental HSV-1(HFEM)tsB7 capsids accumulate at nuclear pores and do not release viral DNA. (iv) The alpha-TK gene chimeras were not induced by infection with spontaneous TK- mutants of pseudorabies virus and bovine mammillitis virus or with human cytomegalovirus or adenovirus type 2 or by exposure to lysates of HSV-1-infected cells from which the virus was removed by centrifugation. These results indicate that the alpha gene inducer is a virion component located outside the capsid and that its function might be to stimulate the transcription of alpha genes by recognizing regulatory sites on viral DNAs or host cell products or both.
Epigenetic virtues of chromodomains (2011)

The chromatin organization modifier domain (chromodomain) was first identified as a motif associated with chromatin silencing in Drosophila. There is growing evidence that chromodomains are evolutionary conserved across different eukaryotic species to control diverse aspects of epigenetic regulation. Although originally reported as histone H3 methyllysine readers, the chromodomain functions have now expanded to recognition of other histone and non-histone partners as well as interaction with nucleic acids. Chromodomain binding to a diverse group of targets is mediated by a conserved substructure called the chromobox homology region. This motif can be used to predict methyllysine binding and distinguish chromodomains from related Tudor "Royal" family members. In this review, we discuss and classify various chromodomains according to their context, structure and the mechanism of target recognition.
The effect of exercise training on human hypertension (1984)

Numerous sources of information in both the medical and exercise physiology areas state that exercise training lowers blood pressure at rest and during submaximal exercise in normotensive and hypertensive individuals. Based on these statements, the medical community is currently recommending regular exercise as a non-pharmacological therapy for reducing blood pressure in hypertensive patients. The purpose of this review was to assess the existing literature in this area to determine whether a basis exists for this recommendation. Our findings indicate that most of the studies reviewed reported modest reductions in blood pressure (means less than or equal to 10 mmHg) at rest and during submaximal exercise after training. However, even the modest reductions in blood pressure reported in these studies must be interpreted with caution because of numerous methodological shortcomings and inadequate study design, most notably the omission of non-exercising hypertensive control groups. Therefore, the evidence available at the present time is inadequate to recommend exercise training as a non-pharmacological therapy in hypertension.
Modern inertial navigation technology and its application (2000)

Inertial navigation technology is used widely for the guidance of aircraft, ships and land vehicles, as well as in an increasing number of civil applications such as robotics, surveying underground well bores and the control of drilling operations. This article describes the techniques and the sensors used in modern systems and outlines a number of applications in which inertial system technology is being used today.
Ion channel diseases (2002)

Ion channels serve many functions apart from electrical signal transduction: chemical signalling (Ca(2+) as a second messenger), transepithelial transport, regulation of cytoplasmic or vesicular ion concentration and pH, and regulation of cell volume. Therefore, ion channel dysfunction can cause diseases in many tissues. The list of human diseases known to be associated with defects in ion channels has grown considerably during the past years. This review gives a short overview of known channelopathies, and focuses in particular on recent findings and on channelopathies that have significantly advanced our physiological insight.
Human DNA Repair Genes (2001)

Cellular DNA is subjected to continual attack, both by reactive species inside cells and by environmental agents. Toxic and mutagenic consequences are minimized by distinct pathways of repair, and 130 known human DNA repair genes are described here. Notable features presently include four enzymes that can remove uracil from DNA, seven recombination genes related to RAD51, and many recently discovered DNA polymerases that bypass damage, but only one system to remove the main DNA lesions induced by ultraviolet light. More human DNA repair genes will be found by comparison with model organisms and as common folds in three-dimensional protein structures are determined. Modulation of DNA repair should lead to clinical applications including improvement of radiotherapy and treatment with anticancer drugs and an advanced understanding of the cellular aging process.
Molecular Cloning and Expression of cDNAs Encoding Mouse $Gal{\beta}$1,3(4)GlcNAc ${\alpha}$2,3-Sialyltransferase (mST3Gal III) and $Gal{\beta}$1,4(3)GlcNAc ${\alpha}$2,3-Sialyltransferase (mST3GaI IV) (1997)

Two kinds of cDNA encoding mouse 1,3(4)GlcNAc 2,3-sialyltransferase (mST3Gal III) and 1,4(3)GlcNAc 2,3-sialyltransferase (mST3Gal IV) were isolated from mouse brain cDNA library by means of a PCR-based approach. The cDNA sequences included an open reading frame coding for proteins of 374 and 333 amino acids, respectively, and the primary structure of these enzymes suggested a putative domain structure consisting of four regions, like that in other glycosyltransferases. The deduced amino acid sequences of mST3GaI III and IV showed a 98% and 89% identity with rat ST3GaI III and human ST3Gal IV, respectively. Northern analysis indicated that the expression of mST3Gal III mRNA was abundant in heart, liver and adult brain, while that of mST3GaI IV mRNA was detected in all tissues tested except for testis, but the level was the highest in liver. Soluble forms of mST3GaI III and IV transiently expressed in COS cells exhibited enzyme activity toward acceptor substrates containing the terminal either 1,3GlcNAc or 1,4GlcNAc sequences. The substrate preferences of both enzymes were stronger for tetrasaccharides than for disaccharides.
Cell growth inhibition by the multifunctional multivalent zinc-finger factor CTCF. (2001)

The 11-zinc finger protein CCTC-binding factor (CTCF) employs different sets of zinc fingers to form distinct complexes with varying CTCF- target sequences (CTSs) that mediate the repression or activation of gene expression and the creation of hormone-responsive gene silencers and of diverse vertebrate enhancer-blocking elements (chromatin insulators). To determine how these varying effects would integrate in vivo, we engineered a variety of expression systems to study effects of CTCF on cell growth. Here we show that ectopic expression of CTCF in many cell types inhibits cell clonogenicity by causing profound growth retardation without apoptosis. In asynchronous cultures, the cell-cycle profile of CTCF-expressing cells remained unaltered, which suggested that progression through the cycle was slowed at multiple points. Although conditionally induced CTCF caused the S-phase block, CTCF can also arrest cell division. Viable CTCF-expressing cells could be maintained without dividing for several days. While MYC is the well-characterized CTCF target, the inhibitory effects of CTCF on cell growth could not be ascribed solely to repression of MYC, suggesting that additional CTS-driven genes involved in growth-regulatory circuits, such as p19ARF, are likely to contribute to CTCF-induced growth arrest. These findings indicate that CTCF may regulate cell-cycle progression at multiple steps within the cycle, and add to the growing evidence for the function of CTCF as a tumor suppressor gene.
E3 Ligase RNF126 Directly Ubiquitinates Frataxin, Promoting Its Degradation: Identification of a Potential Therapeutic Target for Friedreich Ataxia (2017)

Friedreich ataxia (FRDA) is a severe genetic neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin. To date, there is no therapy to treat this condition. The amount of residual frataxin critically affects the severity of the disease; thus, attempts to restore physiological frataxin levels are considered therapeutically relevant. Frataxin levels are controlled by the ubiquitin-proteasome system; therefore, inhibition of the frataxin E3 ligase may represent a strategy to achieve an increase in frataxin levels. Here, we report the identification of the RING E3 ligase RNF126 as the enzyme that specifically mediates frataxin ubiquitination and targets it for degradation. RNF126 interacts with frataxin and promotes its ubiquitination in a catalytic activity-dependent manner, both in vivo and in vitro. Most importantly, RNF126 depletion results in frataxin accumulation in cells derived from FRDA patients, highlighting the relevance of RNF126 as a new therapeutic target for Friedreich ataxia.
S 26948 (2007)

These findings establish S 26948 as a selective PPARgamma ligand with distinctive coactivator recruitment and gene expression profile, reduced adipogenic effect, and improved biological responses in vivo.
Cytotoxic-T-lymphocyte responses to epitopes of listeriolysin O and p60 following infection with Listeria monocytogenes (1996)

In order to test the influence of the cell surface density of a specific H2-Kd-presented epitope on the subsequent level of the cytotoxic-T-lymphocyte (CTL) response directed against the epitope, we investigated the CTL response to two secreted products of Listeria monocytogenes from mice immunized with viable L. monocytogenes. We determined the response to the H2-Kd-presented amino acid 91 to 99 (aa91-99) immunodominant peptide of listeriolysin O (LLO) and to the aa217-225 immunodominant peptide of p60. The p60-derived peptide appears at the cell surface as an H2-Kd-complexed peptide at a level sixfold higher than that of LLO aa91-99. CTL frequency analysis of anti-LLO- or anti-p60-specific CTLs from mice immunized with wild-type L. monocytogenes showed that the numbers of immune spleen cell-derived CTLs specific for the two peptides were essentially equivalent. We have also found that Listeria-specific CTL populations lyse target cells pulsed with the p60 aa217-225 peptide with a magnitude of the lytic response markedly less than that for targets pulsed with the LLO aa91-99 peptide. Additionally, immunization with mutants of L. monocytogenes which do not stimulate anti-LLO-specific CTLs does not alter the CTL frequency of anti-p60-specific effector cells, with levels of anti-p60-specific CTLs similar to those seen in mice immunized with wild-type L. monocytogenes. These results suggest that the relative cell surface density of major histocompatibility complex class I-presented L. monocytogenes-derived epitopes is but one of the criteria which determine the magnitude of the cytotoxic effector cell response that develops in antilisterial immunity.
Surface properties determine bioadhesive outcomes: Methods and results (1984)

This investigation developed experimental evidence for the influence of different surface energy states on tissue incorporation of biomedical materials. Implants of two smooth metals, each with three different surface energy states, were placed in the subdermal fascial plane of the backs of New Zealand White rabbits and were allowed healing times of 10 and 20 days. The implant surfaces were thoroughly characterized by physical-chemical criteria prior to surgical placement and again following removal from the tissue capsules generated by the host animals. Quantitative histopathologic analysis, using standard morphometric criteria, of the adjacent tissues revealed up to a threefold increase of fibroblastic-fibrocytic cells against the initially scrupulously cleaned, high-surface-energy materials. The cells were flattened and active, producing tenacious bonds through a thin pre-adsorbed protein-dominated "conditioning" film, that could be broken only by cohesive failure in the tissue itself. In contrast, the lower-surface-energy materials typical of standard dental implants were "walled off" by a cell-poor, nonadhesive capsule with a fibrous interface separated from a thicker "conditioning" film by a lipid-rich mucus zone. The advantages of proper surface treatment to favor the desired degree of biological adhesion are apparent.
Hypoxia-inducible Factor 1α (HIF-1α) Protein Is Rapidly Degraded by the Ubiquitin-Proteasome System under Normoxic Conditions (1997)

The hypoxia-inducible factor 1 transcriptional activator complex (HIF-1) is involved in the activation of the erythropoietin and several other hypoxia-responsive genes. The HIF-1 complex is composed of two protein subunits: HIF-1beta/ARNT (aryl hydrocarbon receptor nuclear translocator), which is constitutively expressed, and HIF-1alpha, which is not present in normal cells but induced under hypoxic conditions. The HIF-1alpha subunit is continuously synthesized and degraded under normoxic conditions, while it accumulates rapidly following exposure to low oxygen tensions. The involvement of the ubiquitin-proteasome system in the proteolytic destruction of HIF-1 in normoxia was studied by the use of specific inhibitors of the proteasome system. Lactacystin and MG-132 were found to protect the degradation of the HIF-1 complex in cells transferred from hypoxia to normoxia. The same inhibitors were able to induce HIF-1 complex formation when added to normoxic cells. Final confirmation of the involvement of the ubiquitin-proteasome system in the regulated degradation of HIF-1alpha was obtained by the use of ts20TGR cells, which contain a temperature-sensitive mutant of E1, the ubiquitin-activating enzyme. Exposure of ts20 cells, under normoxic conditions, to the non-permissive temperature induced a rapid and progressive accumulation of HIF-1. The effect of proteasome inhibitors on the normoxic induction of HIF-1 binding activity was mimicked by the thiol reducing agent N-(2-mercaptopropionyl)-glycine and by the oxygen radical scavenger 2-acetamidoacrylic acid. Furthermore, N-(2-mercaptopropionyl)-glycine induced gene expression as measured by the stimulation of a HIF-1-luciferase expression vector and by the induction of erythropoietin mRNA in normoxic Hep 3B cells. These last findings strongly suggest that the hypoxia induced changes in HIF-1alpha stability and subsequent gene activation are mediated by redox-induced changes.