gebhart/patrepeval huggingface dataset:
The Binding Interaction of HMG-1 with the TATA-binding Protein/TATA Complex (2001)

High mobility protein-1 (HMG-1) has been shown to regulate transcription by RNA polymerase II. In the context that it acts as a transcriptional repressor, it binds to the TATA-binding protein (TBP) to form the HMG-1/TBP/TATA complex, which is proposed to inhibit the assembly of the preinitiation complex. By using electrophoretic mobility shift assays, we show that the acidic C-terminal domain of HMG-1 and the N terminus of human TBP are the domains that are essential for the formation of a stable HMG-1/TBP/TATA complex. HMG-1 binding increases the affinity of TBP for the TATA element by 20-fold, which is reflected in a significant stimulation of the rate of TBP binding, with little effect on the dissociation rate constant. In support of the binding target of HMG-1 being the N terminus of hTBP, the N-terminal polypeptide of human TBP competes with and inhibits HMG-1/TBP/TATA complex formation. Deletion of segments of the N terminus of human TBP was used to map the region(s) where HMG-1 binds. These findings indicate that interaction of HMG-1 with the Q-tract (amino acids 55-95) in hTBP is primarily responsible for stable complex formation. In addition, HMG-1 and the monoclonal antibody, 1C2, specific to the Q-tract, compete for the same site. Furthermore, calf thymus HMG-1 forms a stable complex with the TBP/TATA complex that contains TBP from either human or Drosophila but not yeast. This is again consistent with the importance of the Q-tract for this stable interaction and shows that the interaction extends over many species but does not include yeast TBP.
The use of lectins to select subpopulations of insect cells (1999)

Lectins have been used in glycoprotein purification, oligosaccharide analysis, and in cell-selection processes. Here, we utilize lectins in a rational attempt to select a subpopulation of insect cells (Estigmene acrea, EAA) with more complete glycosylation capacity by selecting cells that display more complex-type cell-surface oligosaccharides than the general population of cells. A lectin (ECA) from Erythrina cristagalli, specific for galactose beta(1-4)N-acetylglucosamine, was found to be useful in recognizing a small subpopulation of Sf-21 and EAA cells. Cell selections were performed by lectin affinity chromatography and by selective agglutination. Analysis by lectin blots of cell lysates and a quantitative agglutination assay did not reveal significant differences in regard to the level of complex glycosylation between the negatively and positively selected subpopulations of EAA cells. Statistically significant differences in binding the fluorescently labeled lectin, ECA-TRITC were observed even 30 passages post-selection between EAA subpopulations that were negatively and positively selected by lectin affinity chromatography. There were no differences in the two subpopulations in the ECA quantitative agglutination assay. Thus, the hypothesis that a subpopulation differing in glycosylation capacity exists and that such a subpopulation can be identified by the character of cell-surface oligosaccharides is plausible. However, these differences appear to be too small to be of practical use. Copyright 1999 John Wiley & Sons, Inc.
Distribution and function of FSH receptor genetic variants in normal men (2002)

Follicle stimulating hormone (FSH) plays a key role in the maintenance of qualitatively and quantitatively normal spermatogenesis. It controls gamete development through Sertoli cells, via binding to its receptor. The influence and importance of FSH receptor (FSHR) variants on Sertoli cell function is not completely understood and remains to be investigated. In this retrospective study, we explored the impact and action of two distinct FSHR isoforms, Thr307/Asn680 and Ala307/Ser680, in a large group of men. This investigation includes 288 normal healthy men, 86 of whom were proven fathers previously studied, and 202 were newly recruited subjects. The FSHR polymorphism at position 680 was analyzed in the whole group, while position 307 was investigated in 150 subjects, both of them by single-stranded conformation polymorphism (SSCP) gel electrophoresis. The distribution frequency for position 680 was 29% for the Asn/Asn, 52% for the Asn-Ser, 19% for the Ser-Ser variant, and for position 307, 27% for the Thr-Thr, 55% for the Ala-Thr, 18% for the Ala-Ala, respectively. Polymorphism combinations that were different from Thr307/Asn680 - Ala307/Ser680 were found in four subjects. When subjects were grouped according to genotype at position 680, no significant differences between basal FSH, testosterone, inhibin B levels and semen parameters were found. This clinical finding demonstrates that, differently from females, in whom a significant correlation between FSHR polymorphism and basal FSH levels was found, the FSHR genotype has no influence on clinical parameters in males.
Identification of TDRD1 as a direct target gene of ERG in primary prostate cancer (2013)

Molecular classification of ERG-rearranged prostate cancer clarifies the role of TMPRSS2-ERG in the development and progression of prostate cancer. The objective of our study was to identify direct ERG target genes in ERG-rearranged prostate cancer. Two independent cohorts of primary prostate cancer (Cohort A, n=48; Cohort B, n=31), a cohort of late-stage prostate cancer (n=51) and expression array data of a cohort of primary prostate tumors from a different institute (n=128) were analyzed for expression of genes that were coexpressed with ERG overexpression. By genome-wide expression analysis and Q-RT-PCR it was shown that the gene Tudor domain containing 1 (TDRD1) was by far the strongest correlated gene with ERG overexpression in both Cohort A and B. Expression array analysis of the patient cohort from a different institute showed a large overlap in genes that were positively correlated with ERG overexpression, including TDRD1. In late-stage prostate cancer, TDRD1 was also coexpressed with ERG overexpression, although a proportion of ERG-negative late-stage samples expressed TDRD1. TDRD1 expression was not associated with ETV1 overexpression. In the prostate cancer cell line VCaP, downregulation of ERG by shRNA lead to a lower expression level of TDRD1 and resulted in a decreased activity of the TDRD1 promoter. By mutation analysis we identified a functional ERG binding site in the TDRD1 promoter. Our findings show TDRD1 as the first identified upregulated direct ERG target gene that is strongly associated with ERG overexpression in primary prostate cancer.
The virtual notebook system (1991)

Article The virtual notebook system Share on Authors: Andrew M. Burger Baylor College of Medicine, One Baylor Plaza, Houston, Texas Baylor College of Medicine, One Baylor Plaza, Houston, TexasView Profile , Barry D. Meyer Baylor College of Medicine, One Baylor Plaza, Houston, Texas Baylor College of Medicine, One Baylor Plaza, Houston, TexasView Profile , Cindy P. Jung Baylor College of Medicine, One Baylor Plaza, Houston, Texas Baylor College of Medicine, One Baylor Plaza, Houston, TexasView Profile , Kevin B. Long Baylor College of Medicine, One Baylor Plaza, Houston, Texas Baylor College of Medicine, One Baylor Plaza, Houston, TexasView Profile Authors Info & Claims HYPERTEXT '91: Proceedings of the third annual ACM conference on HypertextSeptember 1991 Pages 395–401https://doi.org/10.1145/122974.125119Online:01 September 1991Publication History 13citation333DownloadsMetricsTotal Citations13Total Downloads333Last 12 Months3Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Cytolytic and cytostatic properties of an anti-human Fc γRI (CD64) x epidermal growth factor bispecific fusion protein (1997)

A bispecific fusion protein (H22-EGF) that binds simultaneously to the epidermal growth factor receptor (EGF-R) and to the high affinity receptor for the Fc portion of human IgG, Fc gammaRI (CD64), has been successfully constructed and expressed. For this construction, genomic DNA encoding the Fd fragment of humanized anti-Fc gammaRI mAb, H22, which binds Fc gammaRI at an epitope that is distinct from the Fc binding site, was fused to cDNA encoding human epidermal growth factor (EGF), a natural ligand for EGF-R. The resulting H22Fd-EGF-expressing vector was transfected into a myeloma cell line that was transfected previously with a vector containing DNA encoding the H22 kappa-light chain. SDS-PAGE analysis of purified H22-EGF demonstrated that the fusion protein was secreted predominantly as H22Fab'-EGF monomer (approximately 55 kDa), even though a free Cys residue exists in the hinge region of the H22 Fab' component. Using a novel bispecific flow cytometry-binding assay, we demonstrated that the purified bispecific fusion protein, H22-EGF, was able to bind simultaneously to soluble Fc gammaRI and EGF-R-expressing cells. H22-EGF inhibited the growth of EGF-R-overexpressing tumor cells and mediated dose-dependent cytotoxicity of these cells in the presence of Fc gammaRI-bearing cytotoxic effector cells. These results suggest that this fusion protein may have therapeutic utility for EGF-R-overexpressing malignancies.
Lentiviral Vector–mediated SERCA2 Gene Transfer Protects Against Heart Failure and Left Ventricular Remodeling After Myocardial Infarction in Rats (2008)

Reduced expression of the SERCA2 gene impairs the calcium-handling and contractile functions of the heart. We developed an SERCA2 gene transfer system using lentiviral vectors, and examined the long-term effect of SERCA2 gene transfer in the rat ischemic heart failure model. A lentiviral vector containing the SERCA2 gene was infused into a rat heart by hypothermic intracoronary delivery 2 weeks after myocardial infarction (MI). The transduction efficiency was approximately 40%. Six months after transduction, echocardiogram and pressure-volume measurements revealed that the SERCA2 gene transfer had significantly protected against left ventricular (LV) dilation, and had improved systolic and diastolic function, resulting in reduction in mortality rates. The brain natriuretic peptide mRNA level showed a significantly decrease and the phosphorylation level of serine residue of phospholamban (PLN) showed an increase in the Lenti-SERCA2-transduced heart. Further, DNA microarray analysis disclosed that SERCA2 gene transfer had increased cardioprotective gene expression and lowered the expression of genes that are known to exacerbate heart failure. The SERCA2 gene was successfully integrated into the host heart, induced favorable molecular remodeling, prevented LV geometrical remodeling, and improved the survival rate. These results suggest that a strategy to compensate for reduced SERCA2 gene expression by lentiviral vectors serves as a positive inotropic, lucitropic, and cardioprotective therapy for post-MI heart failure.
A molecular clasp in the human immunodeficiency virus (HIV) type 1 TM protein determines the anti-HIV activity of gp41 derivatives: implication for viral fusion (1995)

We have previously reported that synthetic peptides representing the leucine zipper domain (DP107) and a second putative helical domain (DP178) of human immunodeficiency virus type 1 (HIV-1) gp41 exhibit potent anti-HIV activity. In this study we have used soluble recombinant forms of gp41 to provide evidence that the DP178 peptide and the DP178 region of gp41 associate with a distal site on the gp41 transmembrane protein whose interactive structure is influenced by the leucine zipper (DP107) motif. We also observed that a single coiled-coil-disrupting mutation in the leucine zipper domain transformed the recombinant gp41 protein from an inactive to an active inhibitor of HIV-1 fusion and infectivity, which may be related to that finding. We speculate that this transformation results from liberation of the potent DP178-related sequence from a molecular clasp with a leucine zipper, DP107, determinant. The results are discussed in the context of two distinct conformations for the gp41 molecule and possible involvement of these two domains in structural transitions associated with HIV-1-mediated fusion. The results are also interpreted to suggest that the anti-HIV activity of the various gp41 derivatives (peptides and recombinant proteins) may be due to their ability to form complexes with viral gp41 and interfere with its fusogenic processes.
Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing (2001)

A new cytological tool, based on the microCoulter particle counter (microCPC) principle, aimed at diagnostic applications for cell counting and separation in haematology, oncology or toxicology is described. The device measures the spectral impedance of individual cells or particles and allows screening rates over 100 samples s(-1) on a single-cell basis. This analyzer is intended to drive a sorting actuator producing a subsequent cell separation. Size reduction and integration of functions are essential in achieving precise measurements and high throughput. 3D finite element simulations are presented to compare various electrode geometries and their influence on cell parameters estimation. The device is based on a glass-polyimide microfluidic chip with integrated channels and electrodes microfabricated at the length scale of the particles to be investigated (1-20 microm). A laminar liquid flow carries the suspended particles through the measurement area. Each particle's impedance signal is recorded by a differential pair of microelectrodes using the cell surrounding media as a reference. The micromachined chip and processing electronic circuit allow simultaneous impedance measurements at multiple frequencies, ranging from 100 kHz to 15 MHz. In this paper, we describe the microfabrication and characterisation of an on-chip flow-cytometer as the first building block of a complete cell-sorting device. We then discuss the signal conditioning technique and finally impedance measurements of cells and particles of different sizes and types to demonstrate the differentiation of subpopulations in a mixed sample.
Substituted 3-(phenylmethyl)-1H-indole-5-carboxamides and 1-(phenylmethyl)indole-6-carboxamides as potent, selective, orally active antagonists of the peptidoleukotrienes (1993)

Substituted indole-5-carboxamides and indole-6-carboxamides have been found to be potent and selective antagonists of the peptidoleukotrienes. Initial derivatives of these series (4-[[5-[(cyclopentylmethyl)carbamoyl]-1-methylindol-3-yl] methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (5a) and 4-[[6-[(cyclopentylmethyl)carbamoyl]-3-methylindol-1-yl] methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (6a), respectively), when compared to the corresponding indole amides (e.g. 28 and 29), were found to be approximately 10-fold less potent in vitro and substantially less active when administered orally to guinea pigs. Efforts to improve the potency of the title series by variation of the amide, indole, or sulfonamide substituents led to compounds of comparable in vitro potency to ICI 204,219, but of somewhat lower oral activity. A trend which suggested that more lipophilic transposed amides were needed to increase oral activity was exploited with some success and has led to the discovery of 5q (4-[[5-[(2-ethylbutyl)-carbamoyl]-1-ethylindol-3-yl]methyl]- 3- methoxy-N-[(2-methylphenyl)sulfonyl]benzamide), a transposed amide with subnanomolar affinity for the leukotriene receptor and an oral ED50 of 5 mg/kg in a model of asthma in guinea pigs. In this model, ICI 204,219 was active at 0.4 mg/kg. The absolute bioavailability of 5q has been found to be 28% in the rat, as compared to 68% for ICI 204,219, with significant levels of 5q observed in the blood of rats up to 24 h postdose.
Multichannel Microchip Electrospray Mass Spectrometry (1997)

Microfabricated multiple-channel glass chips were successfully interfaced to an electrospray ionization mass spectrometer (ESI-MS). The microchip device was fabricated by standard photolithographic, wet chemical etching, and thermal bonding procedures. A high voltage was applied individually from each buffer reservoir for spraying sample sequentially from each channel. With the sampling orifice of the MS grounded, it was found that a liquid flow of 100-200 nL/min was necessary to maintain a stable electrospray. The detection limit of the microchip MS experiment for myoglobin was found to be lower than 6 x 10(-8) M. Samples in 75% methanol were successfully analyzed with good sensitivity, as were aqueous samples. The parallel mutliple-channel microchip system allowed ESI-MS analysis of different samples of standard peptides and proteins in one chip.
Vasopressin in Pediatric Vasodilatory Shock: A Multicenter Randomized Controlled Trial (2009)

Low-dose vasopressin did not demonstrate any beneficial effects in this pediatric trial. Although not statistically significant, there was a concerning trend toward increased mortality. Clinical trial registered with www.controlled-trials.com (ISRCTN11597444).
Expression of fibronectin ED-A+ and ED-B+ isoforms by human and experimental colorectal cancer. Contribution of cancer cells and tumor-associated myofibroblasts. (1996)

Alternative splicing of primary fibronectin (FN) mRNA results in the synthesis of different isoforms. ED-A+ and ED-B+ FN isoforms are absent from plasma FN and are representative of cellular FN. Their expression was studied in human and rat normal colon, in human colorectal carcinomas, and in transplanted tumors derived from a chemically-induced rat colon cancer. In normal colon, only the ED-A+ FN isoform was expressed as a thin deposit between crypt colonocytes and pericryptal myofibroblasts. Conversely, heavy ED-A+ FN deposits and lighter ED-B+ FN expression were found in the stroma of colorectal tumors in association with myofibroblasts surrounding tumor glands. Some colonic cancer cells also contained intracellular FN isoform granules and expressed FN mRNA. Tumor-associated myofibroblasts and some cancer cell lines were able to synthesize and deposit extracellular ED-A+ and ED-B+ FN in vitro. FN isoform deposition by tumor-associated myofibroblasts was not modulated by colon cancer cell-conditioned medium, but was strongly enhanced when myofibroblasts were cultured on colon cancer cell extracellular matrix or on laminin. These results show that the ED-A+ and ED-B+ FN isoforms were overexpressed in colorectal cancer. Cancer cells can deposit these FN isoforms directly and also stimulate their deposition by tumor-associated myofibroblasts.
The Fgf Families in Humans, Mice, and Zebrafish: Their Evolutional Processes and Roles in Development, Metabolism, and Disease (2007)

Fibroblast growth factors (Fgfs) were originally isolated as growth factors for fibroblasts. However, Fgfs are now recognized as polypeptide growth factors of ca. 150-250 amino acid residues with diverse biological activities and expression profiles. The Fgf signaling system has been identified in multicelluar but not in unicellular organisms. In contrast to the only two Fgf genes and one Fgf receptor (Fgfr) gene in Caenorhabditis elegans, both the human and mouse Fgf and Fgfr gene families comprise twenty-two and four members, respectively. Their evolutional processes indicate that the Fgf and Fgfr gene families greatly co-expanded during the evolution of early vertebrates. The expansion of the Fgf and Fgfr gene families has enabled this signaling system to acquire diversity of function and a nearly ubiquitous involvement in many developmental and physiological processes. The zebrafish fgf gene family comprises twenty-seven members with several paralogs generated by an additional genome duplication. The mouse and zebrafish are useful models for studying gene functions. Fgf knockout mice have been generated. Several Fgf knockout mice die in the embryonic or early postnatal stages, indicating crucial roles for these genes in various developmental processes. However, other Fgf knockout mice survive with subtle phenotypic alterations. Their functions might be redundant. Studies using zebrafish embryos with mutated or knockdown fgfs also indicate that fgfs play crucial roles in development in that species. Although most Fgfs act in development in a paracrine and/or autocrine manner, some have potential roles in metabolism in an endocrine manner. In humans, Fgf signaling disorders result in hereditary diseases and cancers.
Mediators of the Inflammatory Process (1990)

Introduction. 1. Mediators of the inflammatory process: prostanoids (K.L. Brigham). 2. Leukotriene B 4 (R.R. Gorman). 3. Sulfidopeptide leukotrienes and airway function (M.K. Hodges and J.M. Drazen). 4. Products of 12- and 15-lipoxygenase (W.R. Henderson Jr.). 5. Platelet activating factor: synthesis, metabolism, and relationship to arachidonate products (F.H. Chilton). 6. PAF-acether: biology, receptors and antagonists (B.B. Vargaftig et al.). 7. Transcellular biosynthesis of eicosanoids and (R.C. Murphy, F.A. Fitzpatrick and J. Maclouf). 8. Oxygen radicals as of inflammation (J.S. Warren, P.A. Ward and K.J. Johnson). 9. Mediators of the inflammatory process: vasoactive amines (N.R. Zahniser and D.R. Metcalf). 10. Roles for kinins in (J.M. Stewart). 11. Neuropeptides in and tissue repair (S.M. Aguayo and Y.E. Miller). 12. Interleukins (R.J. Shaw and R.A.F. Clark). 13. Role of platelet-derived growth factor and other growth factors in (N.F. Voelkel). 14. The roles of colony-stimulating factors and interferons in (D.M. Pinson and S.W. Russell). 15. Extracellular matrix components as mediators of (R.M. Senior et al.). 16. Bacterial lipopolysaccharide, a mediator of (M.J. Pabst and R.B. Johnston Jr.). Subject index.
Major Groove Substituents and Polymerase Recognition of a Class of Predominantly Hydrophobic Unnatural Base Pairs (2011)

Expansion of the genetic alphabet with an unnatural base pair is a long-standing goal of synthetic biology. We have developed a class of unnatural base pairs, formed between d5SICS and analogues of dMMO2 that are efficiently and selectively replicated by the Klenow fragment (Kf) DNA polymerase. In an effort to further characterize and optimize replication, we report the synthesis of five new dMMO2 analogues bearing different substituents designed to be oriented into the developing major groove and an analysis of their insertion opposite d5SICS by Kf and Thermus aquaticus DNA polymerase I (Taq). We also expand the analysis of the previously optimized pair, dNaM-d5SICS, to include replication by Taq. Finally, the efficiency and fidelity of PCR amplification of the base pairs by Taq or Deep Vent polymerases was examined. The resulting structure-activity relationship data suggest that the major determinants of efficient replication are the minimization of desolvation effects and the introduction of favorable hydrophobic packing, and that Taq is more sensitive than Kf to structural changes. In addition, we identify an analogue (dNMO1) that is a better partner for d5SICS than any of the previously identified dMMO2 analogues with the exception of dNaM. We also found that dNaM-d5SICS is replicated by both Kf and Taq with rates approaching those of a natural base pair.