gebhart/patrepeval huggingface dataset:
Small molecules that interact with RNA: riboswitch‐based gene control and its involvement in metabolic regulation in plants and algae (2014)

Riboswitches are RNA elements that bind small molecules and in turn regulate gene expression. This mechanism allows the cell to sense the intracellular concentration of these small molecules. A particular riboswitch typically regulates its adjacent gene by altering the transcription, the translation or the splicing of this gene. Recently, a riboswitch that binds thiamin pyrophosphate (TPP) was characterized and found to regulate thiamin biosynthesis in plants and algae. Furthermore, it appears that this element is an essential regulator of primary metabolism in plants. Manipulation of endogenous riboswitch activity resulted in metabolic phenotypes that underlined the role of these elements and their ligands in preserving metabolic homeostasis. This situation supports the hypothesis that riboswitches could be remnants of the most ancient metabolic regulators. Here, we review the mode of action of the plant and algal TPP riboswitch and its relevance to the metabolic network. We also discuss the potential engineering of riboswitches as metabolite sensors in plants and platforms for gene control. Whether additional such RNA-based mechanisms exist in plants and in algae is still an open question, yet, the importance of these elements to metabolic regulation is beyond doubt.
Intracellular immunization (1990)

Following the demonstration that intracellular expression of antibodies ('intracellular immunization') may be utilized to engineer new traits in mammalian cells, we undertook experiments to perturb the function of p21ras proteins, by engineering the intracellular expression of the anti-p21ras antibody Y13-259. The variable regions of this antibody have been cloned and, after verifying their antigen binding activity, expressed in general purpose vectors for the intracellular expression of antibodies. The results confirmed that the cloned antibody has been efficiently expressed both in the secretory and the intracellular forms. Thus, intracellular immunization of mammalian cells against p21ras, or any other antigen for which a monoclonal antibody is available, can now be performed.
The antibiotic and anticancer active aurein peptides from the Australian Bell Frogs Litoria aurea and Litoria raniformis (2000)

Seventeen aurein peptides are present in the secretion from the granular dorsal glands of the Green and Golden Bell Frog Litoria aurea, and 16 from the corresponding secretion of the related Southern Bell Frog L. raniformis. Ten of these peptides are common to both species. Thirteen of the aurein peptides show wide-spectrum antibiotic and anticancer activity. These peptides are named in three groups (aureins 1-3) according to their sequences. Amongst the more active peptides are aurein 1.2 (GLFDIIKKIAESF-NH2), aurein 2.2 (GLFDIVKKVVGALGSL-NH2) and aurein 3.1 (GLFDIVKKIAGHIAGSI-NH2). Both L. aurea and L. raniformis have endoproteases that deactivate the major membrane-active aurein peptides by removing residues from both the N- and C-termini of the peptides. The most abundant degradation products have two residues missing from the N-terminal end of the peptide. The solution structure of the basic peptide, aurein 1.2, has been determined by NMR spectroscopy to be an amphipathic alpha-helix with well-defined hydrophilic and hydrophobic regions. Certain of the aurein peptides (e.g. aureins 1.2 and 3.1) show anticancer activity in the NCI test regime, with LC50 values in the 10-5-10-4 M range. The aurein 1 peptides have only 13 amino-acid residues: these are the smallest antibiotic and anticancer active peptides yet reported from an anuran. The longer aurein 4 and 5 peptides, e.g. aurein 4.1 (GLIQTIKEKLKELAGGLVTGIQS-OH) and aurein 5. 1 (GLLDIVTGLLGNLIVDVLKPKTPAS-OH) show neither antibacterial nor anticancer activity.
Development of a Sensitive and Specific in Situ Hybridization Technique for the Cellular Localization of Antisense Oligodeoxynucleotide Drugs in Tissue Sections (2007)

A sensitive method has been developed for the identification and assessment of phosphorothioate oligonucleotide accumulation in dosed animal tissues using an in situ hybridization approach, which is both sequence specific yet adaptable to every antisense oligonucleotide (ASO), which has been tested to date. Hybridization is accomplished using a digoxigenin-tailed oligonucleotide probe complementary to the ASO target sequence on routinely processed paraffin sections which have been pretreated with a mild target retrieval solution. The DIG-labeled probe is amplified first with an anti-DIG:FITC antibody conjugate followed by an anti:FITC Alexa 488 antibody, then visualized using FITC epifluorescence microscopy. Fluorescent labeling of ASO drug in tissue sections by this method confirms that H&E basophilia previously observed in dosed tissues represents largely intact ASO. However, the fluorescent method enables a wider assessment of tissue distribution in a variety of tissue types due to increased sensitivity and lower signal to noise than can be obtained through an examination of H&E stained tissue sections alone.
The hardwiring of development: organization and function of genomic regulatory systems (1997)

The gene regulatory apparatus that directs development is encoded in the DNA, in the form of organized arrays of transcription factor target sites. Genes are regulated by interactions with multiple transcription factors and the target sites for the transcription factors required for the control of each gene constitute its cis-regulatory system. These systems are remarkably complex. Their hardwired internal organization enables them to behave as genomic information processing systems. Developmental gene regulatory networks consist of the cis-regulatory systems of all the relevant genes and the regulatory linkages amongst them. Though there is yet little explicit information, some general properties of genomic regulatory networks have become apparent. The key to understanding how genomic regulatory networks are organized, and how they work, lies in experimental analysis of cis-regulatory systems at all levels of the regulatory network.
[Present and future therapeutic strategies in rheumatoid arthritis]. (1994)

The triad of inflammation, immunoproliferation and synovial hyperplasia is recognized in the pathogenesis of rheumatoid arthritis, however, the sequence of events remains as highly controversial as ever. The "RA pyramid" was established on the assumption that inflammation is at the top with the destructive processes as sequelae. The moderate successes achieved by conservative therapy with regard to long-term outcome cast doubt on this hypothesis. Inhibitors of prostaglandin synthesis have not been and are not disease modifying. Do substances which influence the endothelial adhesion molecules or leucocyte adhesion receptors (leumedines) promise to be more successful? Do the empirically developed disease modifying antirheumatic drugs (Gold parenteral, MTX) have to be administered earlier? Unfortunately, there is a need for a differential diagnosis which is prognostically valid with regard to the dynamics and aggressiveness of rheumatoid arthritis. Moreover, a pharmacological basis for optimally founded combination strategies is also lacking. Presently, the emphasis of research is directed at the regulation of dysfunctional immune systems. Immunosuppressives (cyclosporin A), cytokine antagonists, receptor antagonists and soluble cytokine receptors (IL-1, IL-6, TNF-alpha), antibodies against lymphocyte subgroups (CD4, CD7) or against cytokines and their receptors are part of the arsenal for the medium term. Too little is still known about the role of protective cytokines (TGF-beta, IL-4, gamma-INF). Currently, however, it is prognosticated that these targeted therapies will only succeed in RA subgroups or only in intelligent combinations. More attractive alternative are strategic therapy modalities which intervene very early in the pathological process, such as the modulation of antigen presentation (MHC blocking peptides, T-cell receptor antagonists, T-cell vaccination) or the induction of tolerance against autoantigens through the oral administration of antigens (collagen II, HSP's, OM-8980). If the center of the pathological process, however, is found in the synovial proliferation of tumor-like cell clusters, then there are only a few years at the beginning of the disease when there is a real chance to impede destruction. In this case, aggressive induction therapy can be the only key to success. In the future, specifically active cytostatics (inhibitors of angiogenesis) will have to be developed and clinical trials conducted on adjuvant therapies with substances which strengthen bone and cartilage, making them more resistant to aggressive cell clusters (bisphosphonates, calcitonins, metalloproteinase- or collagenase-inhibitors).
Modeling and optimization of traveling-wave LiNbO/sub 3/ interferometric modulators (1991)

The characteristics of high-speed LiNbO/sub 3/ electrooptic interferometric modulators/switches are discussed from the viewpoint of optimization of device performance. Specific calculations of the impedance, effective microwave index, and microwave attenuation parameter are presented as a function of the microwave electrode parameters including the buffer layer thickness. The authors have found that the optimization procedure is considerably simplified when the range of electrode and microwave parameters that satisfy a given bandwidth requirement is first determined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Design of a Potentd-Peptide HIV-1 Entry Inhibitor with a Strong Barrier to Resistance (2010)

The HIV gp41 N-trimer pocket region is an ideal viral target because it is extracellular, highly conserved, and essential for viral entry. Here, we report on the design of a pocket-specific D-peptide, PIE12-trimer, that is extraordinarily elusive to resistance and characterize its inhibitory and structural properties. D-peptides (peptides composed of D-amino acids) are promising therapeutic agents due to their insensitivity to protease degradation. PIE12-trimer was designed using structure-guided mirror-image phage display and linker optimization and is the first D-peptide HIV entry inhibitor with the breadth and potency required for clinical use. PIE12-trimer has an ultrahigh affinity for the gp41 pocket, providing it with a reserve of binding energy (resistance capacitor) that yields a dramatically improved resistance profile compared to those of other fusion inhibitors. These results demonstrate that the gp41 pocket is an ideal drug target and establish PIE12-trimer as a leading anti-HIV antiviral candidate.
Signal transduction by glycophorin A: role of extracellular and cytoplasmic domains in a modulatable process. (1988)

Binding of ligands to the extracellular region of the erythrocyte transmembrane protein glycophorin A induces a decrease in membrane deformability. Since the property of membrane deformability is regulated by the skeletal proteins on the cytoplasmic side of the membrane, this suggests that ligand binding may initiate a transmembrane signal. To further study this process, we examined which domains of the extracellular region of glycophorin are involved in signal transduction and whether the cytoplasmic domain of the molecule is necessary for transmitting the signal. Using the ektacytometer, we compared the effect on deformability of four monoclonal antibodies that detect different epitopes on glycophorin A. We found that 9A3 (which recognized the amino terminus of glycophorin) caused a 5.8-fold increase in rigidity, R-10 and 10F7 (which recognized epitopes in the mid-region of the extracellular domain) caused a 10.8-fold increase in rigidity and B14 (which binds to glycophorin close to the membrane) caused a 18-fold increase in rigidity. Further, a direct relationship was observed between the degree of antibody-induced rigidity and the amount of glycophorin A that became associated with the skeletal proteins in a Triton shell assay. In Miltenberger V erythrocytes, which contain a hybrid sialoglycoprotein with no cytoplasmic domain, antibody binding did not induce an increase in rigidity. These results imply that glycophorin A is capable of a modulatable form of transmembrane signaling that is determined by the extracellular domain to which the ligand binds, and the cytoplasmic domain of glycophorin A is crucial for this process.
Direct estimation of time-to-impact from optical flow (2002)

The estimation of time to impact is of vital importance for animals as well as for autonomous robots. The optical flow is used to estimate the time to impact. The authors demonstrate that the motion equations that relate the egomotion and/or the motion of the objects in the scene to the optical flow are considerably simplified if the velocity is represented in a polar or log-polar coordinate system, as opposed to a Cartesian representation. In the former case, the time-to-impact can be directly computed from the velocity field and its derivatives. The analysis takes place considering a tracking egomotion, but is then generalized to arbitrary sensor and object motion. The main result stems from the abundance of equations that can be written directly relating the optical flow, represented in a polar or log-polar coordinate system, with the time-to-impact. Experiments performed on images acquired from real scenes are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides. (2003)

T-cell based immunotherapy is an attractive approach for the treatment of multiple tumor types including cervical carcinoma. Immunostimulating DNA containing unmethylated cytosine-guanine (CpG) motifs have been successfully used as adjuvants to enhance immune responses to vaccines designed to trigger antitumor T-cell responses. Using a murine model of cervical carcinoma, we report here that repeated administration of synthetic oligodeoxynucleotides bearing CpG motifs (CpG-ODNs) without the need of vaccination into animals bearing large, established tumors resulted in significant antitumor effects. Both tumor regressions and extended survival resulting from CpG-ODN therapy required the participation of CD8+ T cells. On the other hand, CD4+ T cells were not only not required, but also appeared to inhibit the therapeutic effect of CpG-ODN. Tumor regression correlated with increased infiltration of CD8+ T cells into the tumors and with enhanced expression of MHC class I and II antigens by the tumor cells. Together, these results indicate that CpG therapy could be promising as a single agent for the treatment of some tumors such as cervical carcinoma.
Analysis of the huntingtin gene reveals a trinucleotide-length polymorphism in the region of the gene that contains two CCG-rich stretches and a correlation between decreased age of onset of Huntington's disease and CAG repeat number (1993)

Journal Article Analysis of the huntingtin gene reveals a trinucleotide-length polymorphism in the region of the gene that contains two CCG-rich stretches and a correlation between decreased age of onset of Huntington's disease and CAG repeat number Get access David C. Rubinsztein, David C. Rubinsztein * East Anglian Regional Genetics Service Molecular Genetics Laboratory, Box 158, Addenbrooke's NHS TrustHills Road, Cambridge CB2 2QQ, UK *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar David E. Barton, David E. Barton East Anglian Regional Genetics Service Molecular Genetics Laboratory, Box 158, Addenbrooke's NHS TrustHills Road, Cambridge CB2 2QQ, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar B.C.Clare Davison, B.C.Clare Davison East Anglian Regional Genetics Service Molecular Genetics Laboratory, Box 158, Addenbrooke's NHS TrustHills Road, Cambridge CB2 2QQ, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Malcolm A. Ferguson-Smith Malcolm A. Ferguson-Smith East Anglian Regional Genetics Service Molecular Genetics Laboratory, Box 158, Addenbrooke's NHS TrustHills Road, Cambridge CB2 2QQ, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 2, Issue 10, October 1993, Pages 1713–1715, https://doi.org/10.1093/hmg/2.10.1713 Published: 01 October 1993 Article history Received: 01 July 1993 Revision received: 02 August 1993 Accepted: 02 August 1993 Published: 01 October 1993
An Expression-Driven Approach to the Prediction of Carbohydrate Transport and Utilization Regulons in theHyperthermophilic Bacterium Thermotoga maritima (2005)

Comprehensive analysis of genome-wide expression patterns during growth of the hyperthermophilic bacterium Thermotoga maritima on 14 monosaccharide and polysaccharide substrates was undertaken with the goal of proposing carbohydrate specificities for transport systems and putative transcriptional regulators. Saccharide-induced regulons were predicted through the complementary use of comparative genomics, mixed-model analysis of genome-wide microarray expression data, and examination of upstream sequence patterns. The results indicate that T. maritima relies extensively on ABC transporters for carbohydrate uptake, many of which are likely controlled by local regulators responsive to either the transport substrate or a key metabolic degradation product. Roles in uptake of specific carbohydrates were suggested for members of the expanded Opp/Dpp family of ABC transporters. In this family, phylogenetic relationships among transport systems revealed patterns of possible duplication and divergence as a strategy for the evolution of new uptake capabilities. The presence of GC-rich hairpin sequences between substrate-binding proteins and other components of Opp/Dpp family transporters offers a possible explanation for differential regulation of transporter subunit genes. Numerous improvements to T. maritima genome annotations were proposed, including the identification of ABC transport systems originally annotated as oligopeptide transporters as candidate transporters for rhamnose, xylose, beta-xylan, and beta-glucans and identification of genes likely to encode proteins missing from current annotations of the pentose phosphate pathway. Beyond the information obtained for T. maritima, the present study illustrates how expression-based strategies can be used for improving genome annotation in other microorganisms, especially those for which genetic systems are unavailable.
Catalysis of N-alkyl-1,4-dihydronicotinamide oxidation by a flavopapain: rapid reaction in all catalytic steps (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCatalysis of N-alkyl-1,4-dihydronicotinamide oxidation by a flavopapain: rapid reaction in all catalytic stepsC. Radziejewski, D. P. Ballou, and Emil Thomas KaiserCite this: J. Am. Chem. Soc. 1985, 107, 11, 3352–3354Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://pubs.acs.org/doi/10.1021/ja00297a054https://doi.org/10.1021/ja00297a054research-articleACS PublicationsRequest reuse permissionsArticle Views70Altmetric-Citations24LEARN 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
Rh-related antigen CD47 is the signal-transducer integrin-associated protein. (1994)

Integrin-associated protein (IAP) is a 50-kDa membrane protein with an amino-terminal immunoglobulin domain and a carboxyl-terminal multiply membrane-spanning region. It is physically and functionally associated with the integrin alpha v beta 3 vitronectin receptor and is involved in the increase in intracellular calcium concentration, which occurs upon cell adhesion to extracellular matrix. Oxidative burst in neutrophils can be induced or inhibited via IAP. Surprisingly, IAP is also expressed on erythrocytes, which have no known integrins. IAP has been shown to be identical to OA3, an ovarian carcinoma antigen. We now show that IAP expression is reduced on Rhnull erythrocytes. The IAP structural gene is mapped to q13.1-2 on human chromosome 3, within a region known to contain a gene encoding the Rh-associated 1D8 antigen. By expression studies on human erythrocytes and IAP transfectants, IAP is shown to be identical to the 1D8 antigen and to CD47, a cell surface protein with broad tissue distribution, reduced in expression on Rhnull erythrocytes. Two CD47 antibodies recognize the immunoglobulin domain of IAP, as does antibody 1D8. These studies suggest the possibility that IAP and the Rh polypeptides may share a pathway for membrane expression on erythrocytes. Furthermore, decreased expression of IAP on Rhnull cells may contribute to the these cells' abnormal cation permeabilities. These studies demonstrate an unexpected link between integrin signal transduction and erythrocyte membrane structure.
Plasma Gelsolin: Function, Prognostic Value, and Potential Therapeutic Use (2008)

Gelsolin is a highly conserved, multifunctional actin-binding protein initially described in the cytosol of macrophages and subsequently identified in many vertebrate cells. A unique property of gelsolin is that in addition to its widely recognized function as a cytoplasmic regulator of actin organization, the same gene expresses a splice variant coding for a distinct isoform, plasma gelsolin, which is secreted into extracellular fluids. The secreted form of gelsolin has been implicated in a number of processes such as the extracellular actin scavenging system and the presentation of lysophosphatidic acid and other inflammatory mediators to their receptors, in addition to its function as a substrate for extracellular matrix-modulating enzymes. Consistent with these proposed functions, blood gelsolin levels decrease markedly in a variety of clinical conditions such as acute respiratory distress syndrome, sepsis, major trauma, prolonged hyperoxia, malaria, and liver injury. This correlation between blood gelsolin levels and critical clinical conditions suggests the potential utility of gelsolin as a prognostic marker as well as the possibility for therapeutic replenishment of gelsolin to alleviate the injurious cascades in these settings. This review summarizes current data supporting a role of plasma gelsolin in extracellular fluids and the potential for its use as a diagnostic marker or therapeutic treatment in several medical conditions.