gebhart/patrepeval huggingface dataset:
A HilA-Independent Pathway to Salmonella typhimurium Invasion Gene Transcription (1999)

Salmonella typhimurium invasion of nonphagocytic cells requires the expression of a type III secretion system (TTSS) encoded within Salmonella pathogenicity island 1 (SPI1). TTSS gene transcription is activated in response to environmental signals and requires transcriptional regulators encoded within (HilA) and outside (SirA) SPI1. Two unique loci, sirB and sirC, which contribute to SPI1 gene transcription were defined. sirC is an SPI1-encoded transcription factor of the AraC family that contributes to the invasive phenotype. sirB is required for maximal expression of sirC and consists of two open reading frames located near kdsA, a gene involved in lipopolysaccharide biosynthesis. sirC expression, unlike expression of other SPI1 genes, does not require HilA. Overexpression of sirC or sirA restores expression of a subset of SPI1 genes, including invF and sspC, in the absence of HilA. These data define roles for SirC and SirA as part of a HilA-independent pathway to SPI1 gene expression. We postulate that HilA-independent activation of inv expression is important for efficient assembly and function of the SPI1 TTSS.
Conformational study of a potent human renin inhibitor: X-ray crystal structure of isopropyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-{N-[(2R)-2-morpholinocarbonylmethyl-3-(1-naphthyl)propionyl]-L-histidylamino}butyrate (KRI-1314), a pentapeptide analogue with amino acid sequence corresponding to the cleavage site of angiotensinogen (1991)

A potent inhibitor of renin, isopropyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-{N-[(2R)-2-morpholino-carbonylmethyl-3-(1-naphthyl)propionyl]-L-histidylamino}butyrate (KRI-1314), was crystallized as a cinnamic acid salt. The crystal structure of KRI-1314 was determined by X-ray analysis, and the conformation is discussed in relation to the inhibitory activity. The backbone chain of the molecule was largely twisted at the unusual amino acid residue of cyclohexylnorstatine. The observed conformation was compared with that of the model pentapeptide corresponding to the scissile site of angiotensinogen. The stacking interaction was formed between the histidine side-chains related by the crystallographic 2-fold screw axis. The histidine imidazole rings were further fixed by hydrogen bonds with the cinnamic acid. The water molecule of crystallization mediated the hydrogen-bonding bridge of the cinnamic acid with the hydroxy oxygen of the cyclohexylnorstatine. Such interactions appear to be very important in considerations of inhibitor-or substrate-binding mechanisms against renin.
Preoperative diagnosis of thyroid papillary and anaplastic carcinomas by real-time quantitative reverse transcription-polymerase chain reaction of oncofetal fibronectin messenger RNA. (1999)

The restricted expression of oncofetal fibronectin (onfFN) mRNA in thyroid papillary and anaplastic carcinomas was recently reported. In this study, we measured the copy number of onfFN mRNA in RNAs extracted from fine needle aspiration biopsies by real-time quantitative reverse transcription-PCR using thyroglobulin mRNA as an internal control. By measuring the onfFN:thyroglobulin mRNA ratio, preoperative aspirates from 31 papillary carcinomas and an anaplastic carcinoma can be distinguished from those from 5 adenomatous goiters, 5 follicular adenomas, and 4 follicular carcinomas. Thus, quantification of onfFN by real-time quantitative reverse transcription-PCR may be useful for the preoperative diagnosis of papillary and anaplastic carcinomas.
Serodiagnosis of Human Granulocytic Ehrlichiosis by Using Novel Combinations of Immunoreactive Recombinant Proteins (2001)

A panel of seven recombinant antigens, derived from Ehrlichia phagocytophila (the agent of human granulocytic ehrlichiosis), was evaluated by class-specific enzyme-linked immunosorbent assays (ELISAs) for utility in the diagnosis of the infection. Fourteen genomic fragments, obtained by serologic expression screening, contained open reading frames (ORFs) encoding 16 immunodominant antigens. Eleven of these antigens were members of the major surface protein (MSP) multigene family. Alignment of their predicted protein sequences revealed a pattern of conserved sequences, which contained short direct repeats, flanking a variable region. In addition, two genomic clones contained two and three MSP ORFs, respectively, indicating that these genes are clustered in tandem copies. The implications for this pattern of both genomic and protein arrangements in antigenic variations of MSPs and in their utilities in a diagnostic assay are discussed. In addition to two MSP recombinant antigens (rHGE-1 and -3) and a fusion protein of these antigens (rErf-1), five further recombinants were evaluated by ELISA. Two of these antigens (rHGE-14 and -15) were novel, while a third (rHGE-2), with no known function, has been described. The final two recombinant antigens (rHGE-9 and -17) represent overlapping segments of the ankyrin gene (ank). The addition of rHGE-9 ELISA data resulted in the detection of 78% (21 of 27) of acute-phase sera. When serologic data for all recombinants are combined, 96.2% (26 of 27) of convalescent-phase patient serum samples and 85.2% (23 of 27) of acute-phase patient serum samples are detected, indicating the potential of these antigens for use in the development of a rapid serologic assay for the detection of E. phagocytophila infection.
Plasma profiling reveals three proteins associated to amyotrophic lateral sclerosis (2014)

Upon further validation in several independent cohorts with inclusion of a broad range of other neurological disorders as controls, the alterations of these three protein profiles in plasma could potentially provide new molecular markers of disease that contribute to the quest of understanding ALS pathology.
Global data on visual impairment in the year 2002. (2004)

This paper presents estimates of the prevalence of visual impairment and its causes in 2002, based on the best available evidence derived from recent studies. Estimates were determined from data on low vision and blindness as defined in the International statistical classification of diseases, injuries and causes of death, 10th revision. The number of people with visual impairment worldwide in 2002 was in excess of 161 million, of whom about 37 million were blind. The burden of visual impairment is not distributed uniformly throughout the world: the least developed regions carry the largest share. Visual impairment is also unequally distributed across age groups, being largely confined to adults 50 years of age and older. A distribution imbalance is also found with regard to gender throughout the world: females have a significantly higher risk of having visual impairment than males. Notwithstanding the progress in surgical intervention that has been made in many countries over the last few decades, cataract remains the leading cause of visual impairment in all regions of the world, except in the most developed countries. Other major causes of visual impairment are, in order of importance, glaucoma, age-related macular degeneration, diabetic retinopathy and trachoma.
The Future of ErbB-1 and ErbB-2 Pathway Inhibition in Breast Cancer: Targeting Multiple Receptors (2004)

The Oncologist 2004;9(suppl 3):1-3 www.TheOncologist.com Correspondence: Dennis J. Slamon, M.D., Ph.D., Department of Medicine, Hematology & Oncology, 3360 Ueberroth Building, Mail Code 707707, Los Angeles, California 90095-7077, USA. Telephone: 310-825-5193; Fax: 310-267-2310; e-mail: dslamon@mednet.ucla.edu Received March 26, 2004; accepted for publication April 15, 2004. ©AlphaMed Press 1083-7159/2004/$12.00/0 There is great enthusiasm in the oncology community over the discovery and use of molecules targeting cellular signaling processes. These processes are essential to cellular functions, including proliferation and differentiation. Many malignancies are characterized by abnormalities in cellular signal transduction, with dysfunction or overexpression of growth factor receptors or other elements of signaling pathways potentially resulting in increased cell survival, proliferation, invasion potential, metastasis, and angiogenesis [1, 2]. This enthusiasm is warranted, despite the fact that it has been tempered by apparent failure in the therapeutic application of some of the molecular-targeted therapies that have been developed. Clear evidence of the promise and success of this approach has been provided in studies of molecules for which we know the target to be operational in the pathogenesis of malignancy and for which drug delivery results in access to and interaction with the target sufficient to provide a pharmacologic effect. It seems likely that many of the apparent failures in therapeutic application are the result of an inability to identify appropriate patient populations—that is, those with target aberrations that are causally sufficient for expression of disease. These failures underscore the need for a better understanding of patient and disease characteristics that increase the likelihood of therapeutic response, as well as a better understanding of how the targeted signaling pathways act individually and interact with one another in the pathogenesis of the disease in which they are being evaluated. Figure 1 provides a simplified schematic of some cell signaling pathways involved in proliferation, transformation, apoptosis, motility, and metastasis and selected moleculartargeted agents that have been developed to inhibit the signaling that induces these processes. What is not made clear in such simplified schematics is that many signaling pathways appear to constitute a highly integrated network rather than a simple linear structure down a single pathway. This allows for considerable crosstalk, networking, and redundancy among pathways in cell signaling. Thus, inhibition of particular receptors known to activate certain pathways may still not result in complete or even significant inhibition of signaling or cell activation. One of the many issues to be confronted in the application of molecular-targeted therapies is whether broader target specificity is more likely to be The Oncologist
Analysis of the intestinal microbiota using SOLiD 16S rRNA gene sequencing and SOLiD shotgun sequencing (2013)

This study shows that SOLiD mate-pair sequencing is a viable and cost-efficient option for analyzing a complex microbiome. To the best of our knowledge, this is the first time that SOLiD sequencing has been used in a human sample.
The Proteolytic Enzymes of the K-1 Strain of Streptomyces griseus Obtained from a Commercial Preparation (Pronase) (1972)

Abstract The commercial protease mixture, Pronase, which is obtained from the K-1 strain of Streptomyces griseus, contains many exo- and endopeptidases. Among the latter enzymes are several which are inhibited by diisopropyl fluorophosphate (DFP). Three of these DFP-reacting components, being of low molecular weight, were partially separated by filtration through Sephadex G-75. Chromatography through CM-cellulose of the filtration fractions with the smaller proteins yielded two well separated peaks (A and B) after the start of a sodium chloride gradient. Peak B consisted of a single enzyme which hydrolyzed N-α-acetyll-tyrosine ethyl ester (Ac-Tyr-OEt). It was homogeneous by gel electrophoresis and its approximate molecular weight was 17,500 as determined by gel filtration. The material in Peak A was heterogeneous with activities against both AcTyr-OEt and N-α-benzoyl-l-arginine ethyl ester (Bz-Arg-OEt). The component which hydrolyzes Bz-Arg-OEt was previously shown to be homologous with mammalian trypsin. Because of reports of the binding of alkylamines by trypsin, rechromatography of components in the earlier peak was carried out in the presence of n-butylamine. Slight retardation of the trypsin-like component was achieved. When a diamine, cadaverine, was substituted for the monoamine, further selective retardation was noted with almost complete resolution of the components in Peak A into two peaks (A1 and A2). These resolutions were thought to be due to the formation of an amine-enzyme complex at the active site; for, if the protein corresponding to Peak A was first reacted with DFP, no retardation was noted. Material from Peak A1 was homogeneous by gel electrophoresis and had an approximate molecular weight of 15,500. It hydrolyzed Ac-Tyr-OEt selectively. As expected the protein corresponding to Peak A2 hydrolyzed Bz-Arg-OEt selectively; its approximate molecular weight was 20,500. This enzyme demonstrated two bands by gel electrophoresis; this heterogeneity was tentatively attributed to the presence of both native enzyme and a partially autolyzed product. A larger DFP-reacting protein which hydrolyzed Ac-Tyr-OEt was partially purified by chromatography through CM-cellulose. Its approximate molecular weight was 27,000. An analysis was made of the partially hydrolyzed [32P]diisopropylphosphoryl (DIP) derivative of this protein. Electrophoretic studies of the migration of the radioactive peptides revealed a significant difference from the pattern of the radioactive peptides of [32P]DIP-α-chymotrypsin. This was in marked contrast to the results obtained with the three smaller enzymes. When a comparative electrophoretic analysis was made with the radioactive peptides of both the new enzyme and the [32P]DIP subtilisins excellent correspondence of patterns was noted. Therefore, the larger enzyme probably contains the sequence Thr-Ser-Met around the reactive seryl residue in contrast to the Asp-Ser-Gly sequences of the smaller enzymes.
Lef1 Transcription Factor Expression Defines Airway Progenitor Cell Targets for In Utero Gene Therapy of Submucosal Gland in Cystic Fibrosis (1998)

Cystic fibrosis (CF) has emerged as a paradigm disorder for assessing the utility of gene therapy in the treatment of genetic diseases. It is hypothesized that submucosal glands may play an important role in the pathophysiology of CF lung disease. However, this region poses several significant obstacles for gene therapy due to its inaccessibility from the lumen of adult proximal airways. In utero gene therapy to correct submucosal gland dysfunction in CF provides an attractive alternative strategy to target gland progenitor cells prior to gland formation and morphogenesis. Such approaches will require the use of integrating vectors capable of transducing expanding stem-cell/progenitor-cell populations in the lung. We described a newborn-ferret model of the proximal airway which was used to evaluate the phenotypic characteristics of submucosal gland progenitors and to test gene therapy strategies for targeting these cell types. To this end, we have isolated the ferret cDNA to the lymphoid enhancing factor 1 (Lef1) and have demonstrated that its mRNA expression specifically defines a subset of surface airway epithelial progenitor cells involved in the formation of primordial submucosal gland buds and subsequent gland morphogenesis. Such findings suggest that the transcriptional switch regulating activation of Lef1 expression defines the phenotype of early submucosal gland progenitor cells. In an effort to prove the principle of gene targeting to this progenitor-cell population, we evaluated the efficiency of recombinant retroviral vectors to target submucosal glands in a xenograft model system. Findings from these studies demonstrated successful gene targeting to progenitor cells of submucosal gland buds which was stable throughout subsequent gland development. In summary, these studies have provided evidence for the existence of phenotypically distinct submucosal gland progenitor cells which represent appropriate targets for gene therapy of submucosal glands in CF.
Human immunodeficiency virus type 1 mRNA expression in peripheral blood cells predicts disease progression independently of the numbers of CD4+ lymphocytes. (1994)

To address the significance of human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells (PBMCs), we have used reverse transcriptase-initiated PCR to measure HIV-1 mRNA expression in PBMC specimens collected from a cohort of HIV-infected individuals during a long-term prospective study. We found dramatic differences in HIV mRNA expression among individuals with very similar clinical and laboratory indices, and this variation strongly correlated with the future course of the disease. No evidence of viral replication was detected in PBMCs from asymptomatic individuals who, thereafter, had normal levels of CD4+ cells for at least 5 years. Irrespective of whether the CD4+ cell numbers were normal at the time of sampling, abundant expression of HIV-1 mRNA in PBMCs predicted accelerated disease progression within the next 2 years. Thus, independently of what may be the rate of HIV replication in other viral reservoirs, such as lymphatic tissue, the amount of HIV mRNA in PBMCs appears to reflect the subsequent development of HIV disease. We have also used the reverse transcriptase-initiated PCR assay to demonstrate a transient response to 3'-azido-3'-deoxythymidine treatment. Determination of HIV-1 mRNA expression in the PBMCs of infected individuals could, therefore, have significant clinical utility as a prognostic indicator and as a means to guiding and monitoring antiviral therapies.
Diffusion Edited NMR:  Screening Compound Mixtures by Affinity NMR to Detect Binding Ligands to Vancomycin (1998)

Affinity NMR can be used to produce an edited NMR spectrum that identifies ligands that bind to vancomycin from solution mixtures containing nonbinding molecules. The Diffusion EnCODEd Spectroscopy (DECODES) experiment performed directly on the same sample can be used to determine the structure of the binding ligands without the need for a physical separation step. The all-d amino acid tetrapeptides DDFA and DDFS, known ligands for vancomycin, were identified in the presence of eight nonbinding tetrapeptides. The bound-ligand signals in the two-dimensional DECODES spectrum are readily identified by comparison with the spectral patterns of the vancomycin cross-peaks in the 2D total correlation spectroscopy and correlation spectroscopy spectra. The screening of solution mixtures of molecules for direct detection of molecular interactions and structural identification of the interacting ligands provides a powerful new tool to complement methods, such as affinity MS, which rely on the physical separation of mixture components to identify molecular interactions. The solution mixtures of compounds for screening by affinity NMR could come from any source where the components are in similar relative amounts, including synthesis by combinatorial chemistry methods.
Inhibin Interferes with Activin Signaling at the Level of the Activin Receptor Complex in Chinese Hamster Ovary Cells (1997)

To gain more insight in the mechanism of action of inhibin, we studied the effect of inhibin on activin signaling in Chinese hamster ovary cells. Inhibin specifically counteracted activin-induced expression of a plasminogen activator inhibitor 1 promoter element (3TP) and of the junB gene, but was ineffective when the responses were induced by transforming growth factor-β. This indicates that inhibin acts only on the activin-specific part of these signaling cascades. Using a constitutively active activin type IB receptor we determined whether inhibin acted at the level of the activin-receptor complex or downstream of it. The mutant activin receptor stimulated the expression of the 3TP promoter in the absence of activin. This stimulation was insensitive to inhibin, indicating that inhibin acts exclusively at or upstream of this activin type I receptor. In addition, competition studies using labeled activin showed that inhibin displaced activin from the activin type II receptors, especially from the activin type IIB receptor, but not from the type I receptors. In conclusion, these data show that in Chinese hamster ovary cells inhibin acts directly at the activin receptor complex, most likely through displacement of activin from the activin type II receptor.
Synthesis of Poly[(amino acid alkyl ester)phosphazenes] (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Poly[(amino acid alkyl ester)phosphazenes]H. R. Allcock, T. J. Fuller, D. P. Mack, K. Matsumura, and Karen M. SmeltzCite this: Macromolecules 1977, 10, 4, 824–830Publication Date (Print):July 1, 1977Publication History Published online1 May 2002Published inissue 1 July 1977https://pubs.acs.org/doi/10.1021/ma60058a020https://doi.org/10.1021/ma60058a020research-articleACS PublicationsRequest reuse permissionsArticle Views847Altmetric-Citations170LEARN 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
Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes (2005)

Concanavalin A (ConA) induces natural killer T (NKT) cell-mediated liver damage. Glucocerebroside (GC) is a naturally occurring glycolipid. Our aims were to determine the effect of GC in a murine model of ConA-induced hepatitis. Mice in groups A and B were treated with GC 2 h before and 2 h following administration of ConA, respectively; group C mice were treated with ConA; group D mice was treated with GC; group E mice did not receive any treatment. Liver damage was evaluated by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver histology. The immune effect of GC was determined by fluorescence-activated cell sorter analysis of intrahepatic and intrasplenic NKT lymphocytes, measurement of cytokine levels, and Western blot analysis for STAT 1, 4, 6, and NF-kappaB expression. The effect of GC on NKT cell proliferation was assessed in vitro. Serum AST and ALT levels were markedly reduced in GC-treated group A mice compared with nontreated group C animals, and histological damage was markedly attenuated in group A. The beneficial effect of GC was associated with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of serum IFN-gamma levels, and decreased STAT1 and STAT6 expression. In vitro administration of GC led to a 42% decrease of NKT cell proliferation in the presence of dendritic cells but not in their absence. Intraperitoneally administered radioactive GC was detected in the liver and bowel. Administration of GC led to amelioration of ConA hepatitis associated with an inhibitory effect on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.