gebhart/patrepeval huggingface dataset:
Atopic Dermatitis Is Associated with a Functional Mutation in the Promoter of the C-C Chemokine RANTES (2000)

Up-regulation of C-C chemokine expression characterizes allergic inflammation and atopic diseases. A functional mutation in the proximal promoter of the RANTES gene has been identified, which results in a new consensus binding site for the GATA transcription factor family. A higher frequency of this allele was observed in individuals of African descent compared with Caucasian subjects (p < 0.00001). The mutant allele was associated with atopic dermatitis in children of the German Multicenter Allergy Study (MAS-90; p < 0.037), but not with asthma. Transient transfections of the human mast cell line HMC-1 and the T cell line Jurkat with reporter vectors driven by either the mutant or wild-type RANTES promoter showed an up to 8-fold higher constitutive transcriptional activity of the mutant promoter. This is the first report to our knowledge of a functional mutation in a chemokine gene promoter. Our findings suggest that the mutation contributes to the development of atopic dermatitis. Its potential role in other inflammatory and infectious disorders, particularly among individuals of African ancestry, remains to be determined.
Endosomal Localization of the Autoantigen EEA1 Is Mediated by a Zinc-binding FYVE Finger (1996)

EEA1, a 162-kDa autoantigen associated with subacute cutaneous systemic lupus erythematosus, is a coiled-coil protein localized to early endosomes and cytosol. At its C terminus, the protein contains a cysteine-rich motif, which is shared with Vps27, Fab1, and Vac1, yeast proteins implicated in membrane traffic (Mu, F. T., Callaghan, J. M., Steele-Mortimer, O., Stenmark, H., Parton, R. G., Campbell, P. L., McCluskey, J., Yeo, J. P., Tock, E. P., and Toh, B. H. (1995) J. Biol. Chem. 270, 13503-13511). Here we show that this motif constitutes a genuine zinc binding domain, which we term the FYVE finger (based on the first letters of four proteins containing this motif). Profile-based data base searches identified the FYVE finger in 11 distinct proteins. The FYVE finger-containing C terminus of EEA1 was found to bind 2 mol equivalents of Zn2+. Mutations of conserved histidine and cysteine residues in the FYVE motif independently reduced zinc binding to 1 mol equivalent. Confocal immunofluorescence microscopy of transfected HEp2 cells revealed that the C-terminal part (residues 1277-1411) of EEA1 colocalizes extensively with a GTPase-deficient mutant of the early endosomal GTPase Rab5, while deletion of the FYVE finger or mutations that interfere with zinc binding cause a cytosolic localization. These results implicate the FYVE finger in the specific localization of EEA1 to endosomes.
Primate digestion: Interactions among anatomy, physiology, and feeding ecology (1998)

Food is vital for life. It provides nutrients for growth, maintenance, and reproduction, and is the source of energy that drives the chemical reactions occurring in every cell.1,2 However, most food, as it is initially procured, is not in a form suitable for use; it must first be broken down so that it can be transported through cell membranes.1 The breaking down of food molecules via a system of both mechanical and chemical processes so that they are of use to the body is called digestion.2,3 © 1998 Wiley-Liss, Inc.
PI3K inhibition in inflammation: Toward tailored therapies for specific diseases (2010)

In the past decade, the availability of genetically modified animals has enabled the discovery of interesting roles for phosphatidylinositol 3-kinase-gamma (PI3Kgamma) and -delta (PI3Kdelta) in different cell types orchestrating innate and adaptive immune responses. Therefore, these PI3K isoforms appear to be attractive drug targets for the treatment of diseases caused by unrestrained immune reactions. Currently, pharmacological targeting of PI3Kgamma and/or PI3Kdelta represents one of the most promising challenges for companies interested in the development of novel safe treatments for inflammatory diseases. In this review we provide a general outline of PI3Kgamma- and PI3Kdelta-specific functions in distinct subsets of inflammatory cells. We also discuss the therapeutic impact of novel compounds targeting PI3Kgamma, PI3Kdelta or both, in mouse models of autoimmune disorders (systemic lupus erythematosus (SLE) and rheumatoid arthritis), respiratory diseases (allergic asthma and chronic obstructive pulmonary disease) and cardiovascular dysfunctions (atherosclerosis and myocardial infarction).
CCAAT/enhancer-binding proteins: structure, function and regulation (2002)

CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that all contain a highly conserved, basic-leucine zipper domain at the C-terminus that is involved in dimerization and DNA binding. At least six members of the family have been isolated and characterized to date (C/EBP alpha[bond]C/EBP zeta), with further diversity produced by the generation of different sized polypeptides, predominantly by differential use of translation initiation sites, and extensive protein-protein interactions both within the family and with other transcription factors. The function of the C/EBPs has recently been investigated by a number of approaches, including studies on mice that lack specific members, and has identified pivotal roles of the family in the control of cellular proliferation and differentiation, metabolism, inflammation and numerous other responses, particularly in hepatocytes, adipocytes and haematopoietic cells. The expression of the C/EBPs is regulated at multiple levels during several physiological and pathophysiological conditions through the action of a range of factors, including hormones, mitogens, cytokines, nutrients and certain toxins. The mechanisms through which the C/EBP members are regulated during such conditions have also been the focus of several recent studies and have revealed an immense complexity with the potential existence of cell/tissue- and species-specific differences. This review deals with the structure, biological function and the regulation of the C/EBP family.
A Reversibly Switching Surface (2003)

We report the design of surfaces that exhibit dynamic changes in interfacial properties, such as wettability, in response to an electrical potential. The change in wetting behavior was caused by surface-confined, single-layered molecules undergoing conformational transitions between a hydrophilic and a moderately hydrophobic state. Reversible conformational transitions were confirmed at a molecular level with the use of sum-frequency generation spectroscopy and at a macroscopic level with the use of contact angle measurements. This type of surface design enables amplification of molecular-level conformational transitions to macroscopic changes in surface properties without altering the chemical identity of the surface. Such reversibly switching surfaces may open previously unknown opportunities in interfacial engineering.
Structure of the Cell Wall Anchor of Surface Proteins in Staphylococcus aureus (1995)

Many surface proteins are anchored to the cell wall of Gram-positive bacteria and are involved in the pathogenesis of these organisms. A hybrid molecule was designed that, when expressed in Staphylococcus aureus, was anchored to the cell wall and could be released by controlled enzymatic digestion. By a combination of molecular biology and mass spectrometry techniques, the structure of the cell wall anchor of surface proteins in S. aureus was revealed. After cleavage of surface proteins between threonine and glycine of the conserved LPXTG motif, the carboxyl of threonine is amide-linked to the free amino group of the pentaglycine crossbridge in the staphylococcal cell wall.
Image reconstruction over a finite field of view* (1975)

The reconstruction of images from profiles has recently received wide attention as the result of the development of x-ray scanners that produce tomograms, or density maps of thin slices through an organ, without the presence of confusing contributions from background or foreground objects situated out of the slice of interest. This very important application to medical imagery now invites further development along many lines. Reduction of scanning time is necessary, both to increase the amount of work that one instrument can do and to permit work on moving organs such as the lungs and heart. Reduction of x-ray dosage is also desirable.
Screening for Colorectal Cancer: A Targeted, Updated Systematic Review for the U.S. Preventive Services Task Force (2008)

Fecal tests with better sensitivity and similar specificity are reasonable substitutes for traditional fecal occult blood testing, although modeling may be needed to determine all tradeoffs. Computed tomographic colonography seems as likely as colonoscopy to detect lesions 10 mm or greater but may be less sensitive for smaller adenomas. Potential radiation-related harms, the effect of extracolonic findings, and the accuracy of test performance of CT colonography in community settings remain uncertain. Emphasis on quality standards is important for implementing any operator-dependent colorectal cancer screening test.
A novel organic-inorganic hybrid monolith for trypsin immobilization (2011)

In proteomics, attention has focused on various immobilized enzyme reactors (IMERs) for the realization of high throughput digestion. In this report, a novel organic-inorganic hybrid monolith based IMER was prepared in a 100 μm i.d. capillary with 3-glycidoxypropyltrimethoxysilane (GLYMO) as the monomer and tetraethoxysilane (TEOS) as the crosslinker. Trypsin immobilization was achieved via the reaction between vicinal diol groups, which were obtained from hydrolysis of epoxy groups, and the amino groups of trypsin. Bovine serum albumin was digested thoroughly by this IMER in 47 s. After micro-reverse phase liquid chromatography-tandem mass spectrometry (μRPLC-MS/MS) analysis and database searching, beyond 35% sequence coverage was obtained, and the result was comparable to that of 12 h in solution digestion. The present IMER has potential for high throughput digestion.
The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells (2012)

We conclude that ovarian cancer cells survive hypoxia by upgrading their stem-like properties through up-regulation of stemness-related factors and behave more aggressively when brought back to higher oxygen environment.
An analytical model of the scattered radiation distribution in diagnostic radiology (1988)

A simple scatter model is used to analytically derive the point spread function (PSF) for scattered radiation in diagnostic radiology. The resulting equation is a function of four physical parameters; object thickness, object-to-detector distance (air gap), and the linear attenuation coefficients for both primary and scatter radiation. Though the model is based upon single scattering, it is shown that by reducing the scatter attenuation coefficient the analytic model compares well to the multiple scattering PSF determined using Monte Carlo analysis.
Characterization of the MeCP2R168X Knockin Mouse Model for Rett Syndrome (2014)

Rett syndrome, one of the most common causes of mental retardation in females, is caused by mutations in the X chromosomal gene MECP2. Mice deficient for MeCP2 recapitulate some of the symptoms seen in patients with Rett syndrome. It has been shown that reactivation of silent MECP2 alleles can reverse some of the symptoms in these mice. We have generated a knockin mouse model for translational research that carries the most common nonsense mutation in Rett syndrome, R168X. In this article we describe the phenotype of this mouse model. In male MeCP2(R168X) mice life span was reduced to 12-14 weeks and bodyweight was significantly lower than in wild type littermates. First symptoms including tremor, hind limb clasping and inactivity occurred at age 27 days. At age 6 weeks nest building, rotarod, open-field and elevated plus maze experiments showed impaired motor performance, reduced activity and decreased anxiety-like behavior. Plethysmography at the same time showed apneas and irregular breathing with reduced frequency. Female MeCP2R168X mice showed no significant abnormalities except decreased performance on the rotarod at age 9 months. In conclusion we show that the male MeCP2(R168X) mice have a phenotype similar to that seen in MECP2 knockout mouse models and are therefore well suited for translational research. The female mice, however, have a much milder and less constant phenotype making such research with this mouse model more challenging.
Mechanism of Autophagy to Apoptosis Switch Triggered in Prostate Cancer Cells by Antitumor Cytokine Melanoma Differentiation-Associated Gene 7/Interleukin-24 (2010)

Melanoma differentiation-associated gene 7 (mda-7)/interleukin-24 (IL-24) is a unique member of the IL-10 gene family, which displays a broad range of antitumor properties, including induction of cancer-specific apoptosis. Adenoviral-mediated delivery by Ad.mda-7 invokes an endoplasmic reticulum (ER) stress response that is associated with ceramide production and autophagy in some cancer cells. Here, we report that Ad.mda-7-induced ER stress and ceramide production trigger autophagy in human prostate cancer cells, but not in normal prostate epithelial cells, through a canonical signaling pathway that involves Beclin-1, atg5, and hVps34. Autophagy occurs in cancer cells at early times after Ad.mda-7 infection, but a switch to apoptosis occurs by 48 hours after infection. Inhibiting autophagy with 3-methyladenosine increases Ad.mda-7-induced apoptosis, suggesting that autophagy may be initiated first as a cytoprotective mechanism. Inhibiting apoptosis by overexpression of antiapoptotic proteins Bcl-2 or Bcl-xL increased autophagy after Ad.mda-7 infection. During the apoptotic phase, the MDA-7/IL-24 protein physically interacted with Beclin-1 in a manner that could inhibit Beclin-1 function culminating in apoptosis. Conversely, Ad.mda-7 infection elicited calpain-mediated cleavage of the autophagic protein ATG5 in a manner that could facilitate switch to apoptosis. Our findings reveal novel aspects of the interplay between autophagy and apoptosis in prostate cancer cells that underlie the cytotoxic action of mda-7/IL-24, possibly providing new insights in the development of combinatorial therapies for prostate cancer.
Internal ribosome entry sites in eukaryotic mRNA molecules (2001)

Initiation of translation of most eukaryotic mRNAs commences with 5 end–dependent recruitment of 40S ribosomal subunits to the mRNA. The 40S subunit carrying the initiator methionine-tRNA and certain eukaryotic initiation factors (eIFs) is thought to scan the mRNA in a 5 to 3 direction until an appropriate start codon is encountered at which stage a 60S subunit joins to form an 80S ribosome that can decode the RNA into protein (Kozak 1989; Hershey and Merrick 2000). A subset of mRNAs contains internal ribosomal entry sites (IRESs), usually in the 5 NTR, that enable end-independent initiation to occur. IRES-containing mRNAs are not subjected to many of the regulatory mechanisms that control recruitment of most mRNAs to the translation apparatus. In this review, we briefly provide an introduction to the known mechanisms of translation initiation. Then, we discuss in detail the molecular mechanisms of IRES-mediated initiation and how they are used by specific mRNAs to permit translation under physiological circumstances such as mitosis, apoptosis, hypoxia, and some viral infections when translation of most mRNAs is repressed.
Characterization of de novo transcriptome for waterhemp (Amaranthus tuberculatus) using GS‐FLX 454 pyrosequencing and its application for studies of herbicide target‐site genes (2010)

These results demonstrate the enormous value of 454 sequencing for gene discovery and polymorphism detection in a major weed species and its relatives. Furthermore, the merging of the 454 transcriptome data with results from a previous whole genome 454 sequencing experiment has made it possible to establish a valuable genomic resource for weed science research.
The splicing factors 9G8 and SRp20 transactivate splicing through different and specific enhancers (1999)

The activity of the SR protein family of splicing factors in constitutive or alternative splicing requires direct interactions with the pre-mRNA substrate. Thus it is important to define the high affinity targets of the various SR species and to evaluate their ability to discriminate between defined RNA targets. We have analyzed the binding specificity of the 30-kDa SR protein 9G8, which contains a zinc knuckle in addition to the RNA binding domain (RBD). Using a SELEX approach, we demonstrate that 9G8 selects RNA sequences formed by GAC triplets, whereas a mutated zinc knuckle variant selects different RNA sequences, centered around a (A/U)C(A/U)(A/U)C motif, indicating that the zinc knuckle is involved in the RNA recognition specificity of 9G8. In contrast, SC35 selects sequences composed of pyrimidine or purine-rich motifs. Analyses of RNA-protein interactions with purified recombinant 30-kDa SR proteins or in nuclear extracts, by means of UV crosslinking and immunoprecipitation, demonstrate that 9G8, SC35, and ASF/SF2 recognize their specific RNA targets with high specificity. Interestingly, the RNA sequences selected by the mutated zinc knuckle 9G8 variant are efficiently recognized by SRp20, in agreement with the fact that the RBD of 9G8 and SRp20 are similar. Finally, we demonstrate the ability of 9G8 and of its zinc knuckle variant, or SRp20, to act as efficient splicing transactivators through their specific RNA targets. Our results provide the first evidence for cooperation between an RBD and a zinc knuckle in defining the specificity of an RNA binding domain.
In search of a thermodynamic description of biomass yields for the chemotrophic growth of microorganisms (1992)

Correlations for the prediction of biomass yields are valuable, and many proposals based on a number of parameters (Y(ATP), Y(Ave), eta(o), Y(c), Gibbs energy efficiencies, and enthalpy efficiencies) have been published. This article critically examines the properties of the proposed parameters with respect to the general applicability to chemotrophic growth systems, a clear relation to the Second Law of Thermodynamics, the absence of intrinsic problems, and a requirement of only black box information. It appears that none of the proposed parameters satisfies all these requirements. Particularly, the various energetic efficiency parameters suffer from major intrinsic problems. However, this article will show that the Gibbs energy dissipation per amount of produced biomass (kJ/C-mod) is a parameter which satisfies the requirements without having intrinsic problems. A simple correlation is found which provides the Gibbs energy dissipation/C-mol biomass as a function of the nature of the C-source (expressed as the carbon chain length and the degree of reduction). This dissipation appears to be nearly independent of the nature of the electron acceptor (e.g., O(2), No(3) (-), fermentation). Hence, a single correlation can describe a very wide range of microbial growth systems. In this respect, Gibbs energy dissipation is much more useful than heat production/C-mol biomass, which is strongly dependent on the electron acceptor used. Evidence is presented that even a net heat-uptake can occur in certain growth systems.The correlation of Gibbs energy dissipation thus obtained shows that dissipation/C-mol biomass increases for C-sources with smaller chain length (C(6) --> C(1)), and increases for both higher and lower degrees of reduction than 4. It appears that the dissipation/C-mol biomass can be regarded as a simple thermodynamic measure of the amount of biochemical "work" required to convert the carbon source into biomass by the proper irreversible carbon-carbon coupling and oxidation/reduction reactions. This is supported by the good correlation between the theoretical ATP requirement for biomass formation on different C-sources and the dissipation values (kJ/C-mol biomass) found. The established correlation for the Gibbs energy dissipation allows the prediction of the chemotrophic biomass yield on substrate with an error of 13% in the yield range 0.01 to 0.80 C-mol biomass/(C)-mol substrate for aerobic/anaerobic/denitrifying growth systems.
An application-specific protocol architecture for wireless microsensor networks (2002)

Networking together hundreds or thousands of cheap microsensor nodes allows users to accurately monitor a remote environment by intelligently combining the data from the individual nodes. These networks require robust wireless communication protocols that are energy efficient and provide low latency. We develop and analyze low-energy adaptive clustering hierarchy (LEACH), a protocol architecture for microsensor networks that combines the ideas of energy-efficient cluster-based routing and media access together with application-specific data aggregation to achieve good performance in terms of system lifetime, latency, and application-perceived quality. LEACH includes a new, distributed cluster formation technique that enables self-organization of large numbers of nodes, algorithms for adapting clusters and rotating cluster head positions to evenly distribute the energy load among all the nodes, and techniques to enable distributed signal processing to save communication resources. Our results show that LEACH can improve system lifetime by an order of magnitude compared with general-purpose multihop approaches.
Regioselective Metalation of Fluoroanilines. An Application to the Synthesis of Fluorinated Oxazolidinone Antibacterial Agents (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRegioselective Metalation of Fluoroanilines. An Application to the Synthesis of Fluorinated Oxazolidinone Antibacterial AgentsKevin C. Grega, Michael R. Barbachyn, Steven J. Brickner, and Stephen A. MizsakCite this: J. Org. Chem. 1995, 60, 16, 5255–5261Publication Date (Print):August 1, 1995Publication History Published online1 May 2002Published inissue 1 August 1995https://pubs.acs.org/doi/10.1021/jo00121a050https://doi.org/10.1021/jo00121a050research-articleACS PublicationsRequest reuse permissionsArticle Views434Altmetric-Citations39LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts