gebhart/patrepeval huggingface dataset:
Tonicity-responsive enhancer binding protein, a Rel-like protein that stimulates transcription in response to hypertonicity (1999)

Hypertonicity (most often present as high salinity) is stressful to the cells of virtually all organisms. Cells survive in a hypertonic environment by increasing the transcription of genes whose products catalyze cellular accumulation of compatible osmolytes. In mammals, the kidney medulla is normally hypertonic because of the urinary concentrating mechanism. Cellular accumulation of compatible osmolytes in the renal medulla is catalyzed by the sodium/myo-inositol cotransporter (SMIT), the sodium/chloride/betaine cotransporter, and aldose reductase (synthesis of sorbitol). The importance of compatible osmolytes is underscored by the necrotic injury of the renal medulla and subsequent renal failure that results from the inhibition of SMIT in vivo by administration of a specific inhibitor. Tonicity-responsive enhancers (TonE) play a key role in hypertonicity-induced transcriptional stimulation of SMIT, sodium/chloride/betaine cotransporter, and aldose reductase. We report the cDNA cloning of human TonE binding protein (TonEBP), a transcription factor that stimulates transcription through its binding to TonE sequences via a Rel-like DNA binding domain. Western blot and immunohistochemical analyses of cells cultured in hypertonic medium reveal that exposure to hypertonicity elicits slow activation of TonEBP, which is the result of an increase in TonEBP amount and translocation to the nucleus.
Breast Tumor Kinase (Protein Tyrosine Kinase 6) Regulates Heregulin-Induced Activation of ERK5 and p38 MAP Kinases in Breast Cancer Cells (2007)

Total tyrosine kinase activity is often elevated in both cytosolic and membrane fractions of malignant breast tissue and correlates with a decrease in disease-free survival. Breast tumor kinase (Brk; protein tyrosine kinase 6) is a soluble tyrosine kinase that was cloned from a metastatic breast tumor and found to be overexpressed in a majority of breast tumors. Herein, we show that Brk is overexpressed in 86% of invasive ductal breast tumors and coexpressed with ErbB family members in breast cancer cell lines. Additionally, the ErbB ligand, heregulin, activates Brk kinase activity. Knockdown of Brk by stable expression of short hairpin RNA (shRNA) in T47D breast cancer cells decreases proliferation and blocks epidermal growth factor (EGF)- and heregulin-induced activation of Rac GTPase, extracellular signal-regulated kinase (ERK) 5, and p38 mitogen-activated protein kinase (MAPK) but not Akt, ERK1/2, or c-Jun NH(2)-terminal kinase. Furthermore, EGF- and heregulin-induced cyclin D1 expression is dependent on p38 signaling and inhibited by Brk shRNA knockdown. The myocyte enhancer factor 2 transcription factor target of p38 MAPK and ERK5 signaling is also sensitive to altered Brk expression. Finally, heregulin-induced migration of T47D cells requires p38 MAPK activity and is blocked by Brk knockdown. These results place Brk in a novel signaling pathway downstream of ErbB receptors and upstream of Rac, p38 MAPK, and ERK5 and establish the ErbB-Brk-Rac-p38 MAPK pathway as a critical mediator of breast cancer cell migration.
A Series of Polyamide Receptor Based PET Fluorescent Sensor Molecules:  Positively Cooperative Hg2+ Ion Binding with High Sensitivity (2006)

[structure: see text] A series of PET fluorescent sensor molecules were designed and synthesized based on BODIPY fluorophore and polyamide receptors. Comparison of the photophysical properties of these sensor molecules, equipped with di-, tri-, and tetraamide receptor, provided a deep insight into the polyamide-Hg2+ interactions, and an unusual positively cooperative tetraamide-Hg2+ complexation was disclosed. In addition, sensor S3 displayed several favorable sensing properties.
Molecular dynamics simulations with experimental restraints (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleMolecular dynamics simulations with experimental restraintsAxel T. Bruenger and Martin KarplusCite this: Acc. Chem. Res. 1991, 24, 2, 54–61Publication Date (Print):February 1, 1991Publication History Published online1 May 2002Published inissue 1 February 1991https://pubs.acs.org/doi/10.1021/ar00002a005https://doi.org/10.1021/ar00002a005research-articleACS PublicationsRequest reuse permissionsArticle Views295Altmetric-Citations98LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Assessing the Validity of Single-layer Regional-scale Modelling of Seawater Intrusion in a Shallow Alluvial Aquifer (2006)

The recent development of a regional-scale seawater intrusion model of the Pioneer Valley, northern Australia has provided a method for assessing the relative groundwater salinity impacts of adopting various water resource management approaches. In order to restrain the heavy computational burden associated with regional-scale seawater intrusion modelling, long term (83 years) predictive simulations adopted a vertically integrated approach, whereby a single-layer model with a relatively coarse model grid resolution (i.e. 250 m cell centres) was used. In this paper, we explore the effects of adopting these simplifying assumptions (i.e. vertical integration and coarse grid resolution) on the prediction of flow and transport processes in the Pioneer Valley coastal plain by comparing the results of the original seawater intrusion model to those of multi-layer, telescoped models, some of which adopt simple representations of the vertical heterogeneities encountered in the coastal plain sediments. The results indicate that, in general, the regional-scale prediction of depth averaged groundwater salinities was only slightly modified by the following: reducing the grid mesh resolution (to 9.3 m cell centres), converting the single-layer model into a three-dimensional (i.e. multilayer) model, or adding vertical heterogeneities. Modifications to the original model produced a maximum salinity bias in the order of 400 S/cm, while the maximum water-table bias was about 0.12 m, these being average values for the entire simulation period of 83 years. However, localised salinity trends were shown to be significantly modified by changes to the model structure, as evidenced by changes to temporal salinity behaviour at discrete locations, and by RMS differences in the prediction of salinity and water-table levels (up to 1100 S/cm and 0.57 m, respectively).
A Sentinel Sensor Network for Hydrogen Sensing (2003)

A wireless sensor network is presented for in-situ monitoring of atmospheric hydrogen concentration. The hydrogen sensor network consists of multiple sensor nodes, equipped with titania nanotube hydrogen sensors, distributed throughout the area of interest; each node is both sensor, and data-relay station that enables extended wide area monitoring without a consequent increase of node power and thus node size. The hydrogen sensor is fabricated from a sheet of highly ordered titania nanotubes, made by anodization of a titanium thick film, to which platinum electrodes are connected. The electrical resistance of the hydrogen sensor varies from 245 Ω at 500 ppm hydrogen, to 10.23 kΩ at 0 ppm hydrogen (pure nitrogen environment). The measured resistance is converted to voltage, 0.049 V at 500 ppm to 2.046 V at 0 ppm, by interface circuitry. The microcontroller of the sensor node digitizes the voltage and transmits the digital information, using intermediate nodes as relays, to a host node that downloads measurement data to a computer for display. This paper describes the design and operation of the sensor network, the titania nanotube hydrogen sensors with an apparent low level resolution of approximately 0.05 ppm, and their integration in one widely useful device.
Amyloid β Protein Gene: cDNA, mRNA Distribution, and Genetic Linkage Near the Alzheimer Locus (1987)

The amyloid beta protein has been identified as an important component of both cerebrovascular amyloid and amyloid plaques of Alzheimer's disease and Down syndrome. A complementary DNA for the beta protein suggests that it derives from a larger protein expressed in a variety of tissues. Overexpression of the gene in brain tissue from fetuses with Down syndrome (trisomy 21) can be explained by dosage since the locus encoding the beta protein maps to chromosome 21. Regional localization of this gene by both physical and genetic mapping places it in the vicinity of the genetic defect causing the inherited form of Alzheimer's disease.
High-Mobility Group Box 1 Mediates Persistent Splenocyte Priming in Sepsis Survivors (2013)

Severe sepsis is a life-threatening complication of infection and injury affecting more than 700,000 people in the United States each year. Two thirds of patients with severe sepsis will survive to be discharged. Survivors have high incidence of cognitive impairment, immune dysregulation, functional impairments with marked disability, and 5-year mortality rates of 82%. High-mobility group box 1 (HMGB1) is necessary and sufficient mediator of sepsis pathogenesis in experimental models of this syndrome. The spleen is a crucial organ in the immune response to severe infection, and splenocyte dysfunction occurs in sepsis survivors. We hypothesized that HMGB1 plays a key role in mediating the immune dysfunction of splenocytes in sepsis survivors. Mice that survived cecal ligation and puncture-induced sepsis develop persistent splenomegaly; furthermore, splenocytes derived from sepsis survivors had enhanced responses to lipopolysaccharide ex vivo. Administration of neutralizing anti-HMGB1 antibody to sepsis survivors attenuated development of splenomegaly and reversed splenocyte priming. Splenocytes exposed to HMGB1 and subsequently challenged with cognate ligands to Toll-like receptor 2 (TLR2,) TLR4, TLR9, and RAGE (receptor for advanced glycation end product) receptors had enhanced cytokine release as compared with splenocytes not previously exposed to HMGB1. Exposure of TLR2, TLR9, or RAGE splenocytes to HMGB1 enhanced responses to other TLR receptor ligands; in contrast, HMGB1 failed to prime TLR4 splenocytes. These findings indicate that exposure to HMGB1 enhances splenocyte responses to secondary inflammatory challenges, a priming effect dependent on TLR4, and that anti-HMGB1 monoclonal antibody may be beneficial in sepsis survivors.
Amino acid sequence of a prothoracicotropic hormone of the silkworm Bombyx mori (1986)

We have determined the complete amino acid sequence of 4K-PTTH-II, one of three forms of the M(r) 4400 prothoracicotropic hormone of the silkworm Bombyx mori, active to brainless pupae of Samia cynthia ricini. Like vertebrate insulin, it consists of two nonidentical peptide chains (A and B chains). The A chain consists of 20 amino acid residues. The B chain is a mixture of four microheterogeneous peptides, two of which consist of 28 residues, and the other two, of 26 residues. 4K-PTTH-II has considerable sequence homology (40%) with human insulin, and it resembles porcine relaxin both in the carboxyl-terminal cysteine residue of the A chain and in the amino-terminal pyroglutamic acid residue of the B chain. The identical distribution of the six cysteine residues also indicates that 4K-PTTH-II belongs to the insulin family.
A National Estimate of the Economic Costs of Asthma (1997)

This cost of illness analysis examines national cost and resource utilization by persons with asthma using a single, comprehensive data source, the 1987 National Medical Expenditure Survey. Direct medical expenditures included payments for ambulatory care visits, hospital outpatient services, hospital inpatient stays, emergency department visits, physician and facility payments, and prescribed medicines. Indirect medical costs included costs resulting from missed work or school and days with restricted activity at work. Point estimates and 95% confidence intervals (CI) were calculated and inflated to 1994 dollars. The total estimated cost was $5.8 billion (95% CI, $3.6 to $8 billion). The estimated direct expenditures were $5.1 billion (95% CI, $3.3 to $7.0 billion), and indirect expenditures were valued at $673 million (95% CI, $271 to $1,076 million). Hospitalization accounted for more than half of all expenditures. More than 80% of resources were used by 20% of the population (defined as 'high-cost patients'). The estimated annual per patient cost for those high-cost patients was $2,584, in contrast with $140 for the rest of the sample. Findings from this study indicate that future asthma research and intervention efforts directed at hospitalizations and high-cost patients could help to decrease health care resource use and provide cost savings.
Methods for whole-cell recording from visually preselected neurons of perirhinal cortex in brain slices from young and aging rats (1998)

This manuscript describes methods for preparing, visualizing, and recording from healthy perirhinal cortex neurons in brain slices from young and aging rats. We focused on perirhinal cortex because of its role in learning, memory, and aging-related cognitive decline. Detailed accounts of our dissection procedures are reported. Procedures that reliably yielded healthy neurons from juvenile rats were not conducive to obtaining healthy, readily-patchable neurons from aging rats, suggesting a procedure-by-age interaction. Performing an intracardiac perfusion, using a temperature-controlled vibratome, matching osmolarity between the cutting and incubation saline, using a slow cutting speed, and incubating slices at a warm temperature for 30 min were important when working with older tissue. Excellent visualization of neurons at depths of up to 100 microm was achieved in slices from all ages (without tissue clearing) avoiding the need to record from surface neurons, which are more likely to have truncated processes. Whole-cell recordings typically remained stable for several hours in neurons prepared from rats at all ages. These procedures should benefit neuroscientists interested in applying visually-guided whole-cell patch-clamp techniques to brain slice experiments using aged tissue. These methods should also facilitate the application of fluorescent imaging technology to brain slices for studying aging-related changes.
Stability-Activity Relationships of a Family of G-tetrad Forming Oligonucleotides as Potent HIV Inhibitors (2000)

Recently, we have demonstrated that T30695, a G-tetrad-forming oligonucleotide, is a potent inhibitor of human immunodeficiency virus, type I (HIV-1) integrase and the K(+)-induced loop folding of T30695 plays a key role in the inhibition of HIV-1 integrase (Jing, N., and Hogan, M. E. (1998) J. Biol. Chem. 273, 34992-34999). Here we have modified T30695 by introducing a hydrophobic bulky group, propynyl dU, or a positively charged group, 5-amino dU, into the bases of T residues of the loops, and by substitution of the T-G loops by T-T loops. Physical measurements have demonstrated that the substitution of propynyl dU or 5-amino dU for T in the T residues of the loops did not alter the structure of T30695, and these derivatives also formed an intramolecular G-quartet structure, which is an essential requirement for anti-HIV activity. Measured IC(50) and EC(50) values show that these substitutions did not induce an apparent decrease in the ability to inhibit HIV-1 integrase activity and in the inhibition of HIV-1 replication in cell culture. However, the substitution of T-T loops for T-G loops induced a substantial decrease in both thermal stability and anti-HIV activity. The data analysis of T30695 and the 21 derivatives shows a significant, functional correlation between thermal stability of the G-tetrad structure and the capacity to inhibit HIV-1 integrase activity and between thermal stability of the G-tetrad structure and the capacity to inhibit HIV-1 replication, as assessed with the virus strains HIV-1 RF, IIIB, and MN in cell culture. This relationship between thermostability and activity provides a basis for improving the efficacy of these compounds to inhibit HIV-1 integrase activity and HIV-1 replication in cell culture.
Interaction of (−)‐epigallocatechin‐3‐gallate with human serum albumin: Fluorescence, fourier transform infrared, circular dichroism, and docking studies (2006)

(-)-Epigallocatechin-3-gallate (EGCG), the major constituent of green tea has been reported to prevent many diseases by virtue of its antioxidant properties. The binding of EGCG with human serum albumin (HSA) has been investigated for the first time by using fluorescence, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, and protein-ligand docking. We observed a quenching of fluorescence of HSA in the presence of EGCG. The binding parameters were determined by a Scatchard plot and the results were found to be consistent with those obtained from a modified Stern-Volmer equation. From the thermodynamic parameters calculated according to the van't Hoff equation, the enthalpy change deltaH degrees and entropy change deltaS degrees were found to be -22.59 and 16.23 J/mol K, respectively. These values suggest that apart from an initial hydrophobic association, the complex is held together by van der Waals interactions and hydrogen bonding. Data obtained by fluorescence spectroscopy, CD, and FTIR experiments along with the docking studies suggest that EGCG binds to residues located in subdomains IIa and IIIa of HSA. Specific interactions are observed with residues Trp 214, Arg 218, Gln 221, Asn 295 and Asp 451. We have also looked at changes in the accessible surface area of the interacting residues on binding EGCG for a better understanding of the interaction.
Isolation and characterization of the Fc receptor from the fetal yolk sac of the rat. (1990)

The yolk sac of the fetal rat and the proximal small intestine of the neonatal rat selectively transport maternal IgG. IgG-Fc receptors are thought to mediate transport across the epithelium of both tissues. We used a mouse mAb (MC-39) against the 45-54-kD component of the Fc receptor of the neonatal intestine to find an antigenically related protein that might function as an Fc receptor in fetal yolk sac. In immunoblots of yolk sac, MC-39 recognized a protein band with apparent molecular mass of 54-58 kD. MC-39 bound to the endoderm of yolk sac in immunofluorescence studies. In immunogold-labeling experiments MC-39 was associated mainly with small vesicles in the apical cytoplasm and in the region near the basolateral membrane of endodermal cells. The MC-39 cross-reactive protein and beta 2-microglobulin, a component of the intestinal Fc receptor, were copurified from detergent-solubilized yolk sac by an affinity purification that selected for proteins which, like the intestinal receptor, bound to IgG at pH 6.0 and eluted at pH 8.0. In summary, the data suggest that we have isolated the Fc receptor of the yolk sac and that this receptor is structurally and functionally related to the Fc receptor of the neonatal intestine. An unexpected finding is that, unlike the intestinal receptor which binds maternal IgG on the apical cell surface, the yolk sac receptor appears to bind IgG only within apical compartments which we suggest represent the endosomal complex.
BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet (2011)

Mutations in the Bcr-Abl kinase domain may cause, or contribute to, resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia patients. Recommendations aimed to rationalize the use of BCR-ABL mutation testing in chronic myeloid leukemia have been compiled by a panel of experts appointed by the European LeukemiaNet (ELN) and European Treatment and Outcome Study and are here reported. Based on a critical review of the literature and, whenever necessary, on panelists' experience, key issues were identified and discussed concerning: (1) when to perform mutation analysis, (2) how to perform it, and (3) how to translate results into clinical practice. In chronic phase patients receiving imatinib first-line, mutation analysis is recommended only in case of failure or suboptimal response according to the ELN criteria. In imatinib-resistant patients receiving an alternative TKI, mutation analysis is recommended in case of hematologic or cytogenetic failure as provisionally defined by the ELN. The recommended methodology is direct sequencing, although it may be preceded by screening with other techniques, such as denaturing-high performance liquid chromatography. In all the cases outlined within this abstract, a positive result is an indication for therapeutic change. Some specific mutations weigh on TKI selection.
Zfp488 promotes oligodendrocyte differentiation of neural progenitor cells in adult mice after demyelination (2011)

Basic helix-loop-helix transcription factors Olig1 and Olig2 critically regulate oligodendrocyte development. Initially identified as a downstream effector of Olig1, an oligodendrocyte-specific zinc finger transcription repressor, Zfp488, cooperates with Olig2 function. Although Zfp488 is required for oligodendrocyte precursor formation and differentiation during embryonic development, its role in oligodendrogenesis of adult neural progenitor cells is not known. In this study, we tested whether Zfp488 could promote an oligodendrogenic fate in adult subventricular zone (SVZ) neural stem/progenitor cells (NSPCs). Using a cuprizone-induced demyelination model in mice, we examined the effect of retrovirus-mediated Zfp488 overexpression in SVZ NSPCs. Our results showed that Zfp488 efficiently promoted the differentiation of the SVZ NSPCs into mature oligodendrocytes in vivo. After cuprizone-induced demyelination injury, Zfp488-transduced mice also showed significant restoration of motor function to levels comparable to control mice. Together, these findings identify a previously unreported role for Zfp488 in adult oligodendrogenesis and functional remyelination after injury.