gebhart/patrepeval huggingface dataset:
Kinetic Mechanism for the Binding of eIF4F and Tobacco Etch Virus Internal Ribosome Entry Site RNA (2009)

The wheat germ eukaryotic translation initiation factor (eIF) 4F binds tightly to the mRNA internal ribosome entry site (IRES) of tobacco etch virus (TEV) to promote translation initiation. When eIF4F is limiting, TEV is preferentially translated compared with host cell mRNA. To gain insight into the dynamic process of protein synthesis initiation and the mechanism of binding, the kinetics of eIF4F binding to TEV IRES were examined. The association rate constant (k(on)) and dissociation rate constant (k(off)) for eIF4F binding to IRES were 59 +/- 2.1 micro s(-1) and 12.9 +/- 0.3 s(-1), respectively, comparable with the rates for capped RNA. Binding of eIF4E or eIF4F to the cap of mRNA is the rate-limiting step for initiation of cap-dependent protein synthesis. The concentration dependence of the reactions suggested a simple one-step association mechanism. However, the association rate was reduced more than 10-fold when KCl concentration was increased from 50 to 300 mm, whereas the dissociation rate constant was increased 2-fold. The addition of eIF4B and poly(A)-binding protein enhanced the association rate of eIF4F approximately 3-fold. These results suggest a mechanism where eIF4F initially binds electrostatically, followed by a conformational change to further stabilize binding. Poly(A)-binding protein and eIF4B mainly affect the eIF4F/TEV association rate. These results demonstrate the first direct kinetic measurements of translation initiation factor binding to an IRES.
Ultralow Fouling Zwitterionic Polymers Grafted from Surfaces Covered with an Initiator via an Adhesive Mussel Mimetic Linkage (2008)

In this work, nonfouling zwitterionic polymers were grafted via surface-initiated atom transfer radical polymerization (ATRP) from surfaces covered with an adhesive catechol initiator. The catechol initiator was attached to both bare gold and amino-functionalized surfaces, and the nonfouling performances of the resulting polymer brushes were compared. Under optimal conditions, ultralow protein adsorption from both single-protein solutions of fibrinogen and lysozyme and complex media of 10% blood serum and 100% blood plasma/serum was achieved. Furthermore, the 3-day accumulation of Pseudomonas aeruginosa on the treated glass surfaces was studied in situ using a laminar flow chamber. The results showed that these zwitterionic coatings dramatically reduced the biofilm formation of P. aeruginosa as compared to the reference bare glass.
New Chiral Ruthenium Bis(oxazolinyl)pyridine Catalyst. Efficient Asymmetric Cyclopropanation of Olefins with Diazoacetates (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Chiral Ruthenium Bis(oxazolinyl)pyridine Catalyst. Efficient Asymmetric Cyclopropanation of Olefins with DiazoacetatesHisao Nishiyama, Yoshiki Itoh, Hideki Matsumoto, Soon-Bong Park, and Kenji ItohCite this: J. Am. Chem. Soc. 1994, 116, 5, 2223–2224Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://doi.org/10.1021/ja00084a104RIGHTS & PERMISSIONSArticle Views2124Altmetric-Citations358LEARN 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 InReddit PDF (268 KB) Get e-Alerts Get e-Alerts
Hydroaromatic Equilibration During Biosynthesis of Shikimic Acid (2001)

The expense and limited availability of shikimic acid isolated from plants has impeded utilization of this hydroaromatic as a synthetic starting material. Although recombinant Escherichia coli catalysts have been constructed that synthesize shikimic acid from glucose, the yield, titer, and purity of shikimic acid are reduced by the sizable concentrations of quinic acid and 3-dehydroshikimic acid that are formed as byproducts. The 28.0 g/L of shikimic acid synthesized in 14% yield by E. coli SP1.1/pKD12.138 in 48 h as a 1.6:1.0:0.65 (mol/mol/mol) shikimate/quinate/dehydroshikimate mixture is typical of synthesized product mixtures. Quinic acid formation results from the reduction of 3-dehydroquinic acid catalyzed by aroE-encoded shikimate dehydrogenase. Is quinic acid derived from reduction of 3-dehydroquinic acid prior to synthesis of shikimic acid? Alternatively, does quinic acid result from a microbe-catalyzed equilibration involving transport of initially synthesized shikimic acid back into the cytoplasm and operation of the common pathway of aromatic amino acid biosynthesis in the reverse of its normal biosynthetic direction? E. coli SP1.1/pSC5.214A, a construct incapable of de novo synthesis of shikimic acid, catalyzed the conversion of shikimic acid added to its culture medium into a 1.1:1.0:0.70 molar ratio of shikimate/quinate/dehydroshikimate within 36 h. Further mechanistic insights were afforded by elaborating the relationship between transport of shikimic acid and formation of quinic acid. These experiments indicate that formation of quinic acid during biosynthesis of shikimic acid results from a microbe-catalyzed equilibration of initially synthesized shikimic acid. By apparently repressing shikimate transport, the aforementioned E. coli SP1.1/pKD12.138 synthesized 52 g/L of shikimic acid in 18% yield from glucose as a 14:1.0:3.0 shikimate/quinate/dehydroshikimate mixture.
Intracellular CA2+ response of rabbit oocytes to electrical stimulation (1992)

Electrical stimulation is known to cause activation in mammalian oocytes, possibly by eliciting an elevation in intracellular calcium (Ca2+). This study reports intracellular Ca2+ concentrations in mature rabbit oocytes using the Ca2+ indicator fura-2. Calcium levels were determined prior to, during, and after the administration of an electrical pulse (3.6 kV/cm for 60 microseconds). Baseline Ca2+ levels ranged from 30 to 90 nM. The intracellular Ca2+ transient evoked by a pulse, peaked at 11 sec, was highly variable in amplitude (40-300 nM) and returned to prepulse levels within 300 sec. Electrically stimulated oocytes did not exhibit repetitive Ca2+ transients. The size of the cytoplasmic Ca2+ rise was influenced by the duration of the pulse, the field strength and the concentrations of external Ca2+ rise was influenced by the duration of the pulse, the field strength and the concentrations of external Ca2+ (P less than 0.05). Oocytes electrically stimulated in the presence of 100 microM CaCl2, which evoked Ca2+ transients with a mean magnitude of 120 nM, activated at a higher rate (P less than 0.05) than oocytes stimulated in the presence of either higher or lower levels of external Ca2+. Although oocytes electrically shocked at 16-18 hr after administration of human chorionic gonadotropin (hphCG) activated at a lower rate than oocytes stimulated at 22-24 hphCG (P less than 0.05), their intracellular Ca2+ response to the pulse was similar (P less than 0.05). These results indicate that electrical pulse parameters and extracellular Ca2+ concentrations can be used to modulate intracellular Ca2+ levels and optimize oocyte activation rates.(ABSTRACT TRUNCATED AT 250 WORDS)
Potent Antagonists of the SH2 Domain of Grb2:  Optimization of the X+1 Position of 3-Amino-Z-Tyr(PO3H2)-X+1-Asn-NH2 (1998)

ADVERTISEMENT RETURN TO ISSUELetterNEXTPotent Antagonists of the SH2 Domain of Grb2: Optimization of the X+1 Position of 3-Amino-Z-Tyr(PO3H2)-X+1-Asn-NH2Carlos García-Echeverría, Pascal Furet, Brigitte Gay, Heinz Fretz, Joseph Rahuel, Joseph Schoepfer, and Giorgio CaravattiView Author Information Oncology Research and Core Technology Area, Novartis Pharma Inc., CH-4002 Basel, Switzerland Cite this: J. Med. Chem. 1998, 41, 11, 1741–1744Publication Date (Web):April 28, 1998Publication History Received22 December 1997Published online28 April 1998Published inissue 1 May 1998https://pubs.acs.org/doi/10.1021/jm970856nhttps://doi.org/10.1021/jm970856nrapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views277Altmetric-Citations42LEARN 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 (1)»Supporting Information Supporting Information SUBJECTS:Antagonists,Conformation,Monomers,Peptides and proteins,Screening assays Get e-Alerts
Premature Aging in Mice Deficient in DNA Repair and Transcription (2002)

One of the factors postulated to drive the aging process is the accumulation of DNA damage. Here, we provide strong support for this hypothesis by describing studies of mice with a mutation in XPD, a gene encoding a DNA helicase that functions in both repair and transcription and that is mutated in the human disorder trichothiodystrophy (TTD). TTD mice were found to exhibit many symptoms of premature aging, including osteoporosis and kyphosis, osteosclerosis, early greying, cachexia, infertility, and reduced life-span. TTD mice carrying an additional mutation in XPA, which enhances the DNA repair defect, showed a greatly accelerated aging phenotype, which correlated with an increased cellular sensitivity to oxidative DNA damage. We hypothesize that aging in TTD mice is caused by unrepaired DNA damage that compromises transcription, leading to functional inactivation of critical genes and enhanced apoptosis.
Receptor binding of asialoerythropoietin (1992)

The interaction of 125I-asialoerythropoietin (asialoepo) with receptors has been characterized both by binding assay and affinity cross-linking. Purified spleen cells from mice infected with the anemia strain of Friend virus (FVA cells) have receptors for 125I-asialoepo with two classes of affinity constant: one with Kd = 0.02-0.03 nM and 300-400 per cell, the other with lower affinity (Kd = 0.9-1.2 nM) and 1,000-1,200 per cell. The Kd value for the high affinity site is one-third of that for the binding of native 125I-erythropoietin (125I-epo) to the same FVA cells (Kd = 0.08-0.1 nM). Using 125I-asialoepo or 125I-epo affinity cross-linking methods, we find two components with apparent molecular weights of 88 kDa and 105 kDa in FVA cells, and in the transformed mouse cell lines, 201, IW32, and NN10, in agreement with earlier studies using 125I-epo. These results indicate that 125I-asialoepo binds to the same receptors as 125I-epo, but with greater affinity for the high affinity site. Since 201 cells contain only a single class of lower affinity receptors for erythropoietin (epo), finding the same two components as found for FVA cells by cross-linking experiment indicates that the two components do not represent the two classes of receptor.
Promoter Hypermethylation and BRCA1 Inactivation in Sporadic Breast and Ovarian Tumors (2000)

Silencing of the BRCA1 gene by promoter hypermethylation occurs in primary breast and ovarian carcinomas, especially in the presence of LOH and in specific histopathologic subgroups. These findings support a role for this tumor suppressor gene in sporadic breast and ovarian tumorigenesis.
microRNA-497 Modulates Breast Cancer Cell Proliferation, Invasion, and Survival by Targeting SMAD7 (2016)

As an inhibitor of TGF-β signaling, SMAD7 was reported to play dual roles in breast cancer development and progression. It inhibited the cancer metastasis by blocking epithelial-mesenchymal transition, however, litter studies focused on its role in other cancer processes. In this study, miR-497 expression was found inversely correlated with SMAD7 expression in breast cancer tissues. Bioinformatics analyses defined a potential miR-497 response element within 3' untranslated region of SMAD7 that was validated in reporter gene experiments. Enforced miR-497 expression, accompanied with SMAD7 reduction, suppressed MDA-MB-231 and MCF-7 breast cancer cell growth by MTT and invasion assay, and, induced the S phase arrest detected by flow cytometry. Furthermore, upregulated miR-497 expression by mimics treatment significantly suppressed the tumor growth in the orthotopic nude mouse models. Finally, high expression of miR-497 conferred a better prognosis, indicated by Kaplan-Meier test, especially in HER2 overexpression and triple-negative breast cancer (TNBC). Taken together, our results identified the proliferation promoting role of SMAD7 in breast cancer and therefore established the regulations of SMAD7 in breast cancer by miR-497 through a posttranscriptional mechanism. Moreover, miR-497 might be deemed as a novel potential therapeutic target for the HER2 positive and TNBC in future.
Ceragenins: Cholic Acid-Based Mimics of Antimicrobial Peptides (2008)

The prevalence of drug-resistant bacteria drives the quest for new antimicrobials, including those that are not expected to readily engender resistance. One option is to mimic Nature's most ubiquitous means of controlling bacterial growth, antimicrobial peptides, which have evolved over eons. In general, bacteria remain susceptible to these peptides. Human antimicrobial peptides play a central role in innate immunity, and deficiencies in these peptides have been tied to increased rates of infection. However, clinical use of antimicrobial peptides is hampered by issues of cost and stability. The development of nonpeptide mimics of antimicrobial peptides may provide the best of both worlds: a means of using the same mechanism chosen by Nature to control bacterial growth without the problems associated with peptide therapeutics. The ceragenins were developed to mimic the cationic, facially amphiphilic structures of most antimicrobial peptides. These compounds reproduce the required morphology using a bile-acid scaffolding and appended amine groups. The resulting compounds are actively bactericidal against both gram-positive and gram-negative organisms, including drug-resistant bacteria. This antimicrobial activity originates from selective association of the ceragenins with negatively charged bacterial membrane components. Association has been studied with synthetic models of bacterial membrane components, with bacterial lipopolysaccharide, with vesicles derived from bacterial phospholipids, and with whole cells. Comparisons of the antimicrobial activities of ceragenins and representative antimicrobial peptides suggest that these classes of compounds share a mechanism of action. Rapid membrane depolarization is caused by both classes as well as blebbing of bacterial membranes. Bacteria express the same genes in response to both classes of compounds. On the basis of the antibacterial activities of ceragenins and preliminary in vivo studies, we expect these compounds to find use in augmenting or replacing antimicrobial peptides in treating human disease.
Efficient Generic Calibration Method for General Cameras with Single Centre of Projection (2007)

Generic camera calibration is a non-parametric calibration technique that is applicable to any type of vision sensor. However, the standard generic calibration method was developed with the goal of generality and it is therefore sub-optimal for the common case of cameras with a single centre of projection (e.g. pinhole, fisheye, hyperboloidal catadioptric). This paper proposes novel improvements to the standard generic calibration method for central cameras that reduce its complexity, and improve its accuracy and robustness. Improvements are achieved by taking advantage of the geometric constraints resulting from a single centre of projection. Input data for the algorithm is acquired using active grids, the performance of which is characterised. A new linear estimation stage to the generic algorithm is proposed incorporating classical pinhole calibration techniques, and it is shown to be significantly more accurate than the linear estimation stage of the standard method. A linear method for pose estimation is also proposed and evaluated against the existing polynomial method. Distortion correction and motion reconstruction experiments are conducted with real data for a hyperboloidal catadioptric sensor for both the standard and proposed methods. Results show the accuracy and robustness of the proposed method to be superior to those of the standard method.
Mammalian glutaminyl cyclases and their isoenzymes have identical enzymatic characteristics (2009)

Glutaminyl cyclases (QCs) catalyze the formation of pyroglutamate residues at the N-terminus of several peptides and proteins from plants and animals. Recently, isoenzymes of mammalian QCs have been identified. In order to gain further insight into the biochemical characteristics of isoQCs, the human and murine enzymes were expressed in the secretory pathway of Pichia pastoris. Replacement of the N-terminal signal anchor by an alpha-factor prepropeptide from Saccharomyces cerevisiae resulted in poor secretion of the protein. Insertion of an N-terminal glycosylation site and shortening of the N-terminus improved isoQC secretion 100-fold. A comparison of different recombinant isoQC proteins did not reveal an influence of mutagenic changes on catalytic activity. An initial characterization showed identical modes of substrate conversion of human isoQC and murine isoQC. Both proteins displayed a broad substrate specificity and preference for hydrophobic substrates, similar to the related QC. Likewise, a determination of the zinc content and reactivation of the apo-isoQC revealed equimolar zinc present in QC and isoQC. Far-UV CD spectroscopic analysis of murine QC and isoQC indicated virtually identical structural components. The present investigation provides the first enzymatic characterization of mammalian isoQCs. QC and isoQC represent very similar proteins, which are both present in the secretory pathway of cells. The functions of QCs and isoQC probably complement each other, suggesting a pivotal role of pyroglutamate modification for protein and peptide maturation.
Real-time 3D pulse-echo ultrasonic imaging with coded-excitation systems (2002)

A new coded-excitation pulse-echo imaging system capable of simultaneous acquisition of a larger number of image lines for real-time 3D imaging is presented. A theoretical formulation of the system based on a discretized received signal model is given. With realistic simplifications, the image reconstruction is realized by a transversal filter bank with each filter designed to extract echoes from a specific direction in the region of interest. The filters are derived from a regularized pseudoinverse image reconstruction operator obtained from the system formulation. Unlike similar coded-excitation systems based on matched filtering, this pseudoinverse-based filter bank decouples echoes from different directions before providing matched filtering along the range direction. The correlation artifacts due to non-ideal coding are thus dramatically reduced. It can also be shown that the system may achieve lateral resolution exceeding the limit of conventional beamforming systems based on the same array. Both simulation and experimental results are provided.
Regulation of a Cytosolic and Nuclear O-GlcNAc Transferase (1999)

The O-GlcNAc transferase (OGT) is a unique nuclear and cytosolic glycosyltransferase that contains multiple tetratricopeptide repeats. We have begun to characterize the mechanisms regulating OGT using a combination of deletion analysis and kinetic studies. Here we show that the p110 subunit of the enzyme forms both homo- and heterotrimers that appear to have different binding affinities for UDP-GlcNAc. The multimerization domain of OGT lies within the tetratricopeptide repeat domain and is not necessary for activity. Kinetic analyses of the full-length trimer and the truncated monomer forms of OGT suggest that both forms function through a random bi-bi kinetic mechanism. Both the monomer and trimer have similar specific activities and similar K(m) values for peptide substrates. However, they differ in their binding affinities for UDP-GlcNAc, indicating that subunit interactions affect enzyme activity. The findings that recombinant OGT has three distinct K(m) values for UDP-GlcNAc and that UDP-GlcNAc concentrations modulates the affinity of OGT for peptides suggest that OGT is exquisitely regulated by the levels of UDP-GlcNAc within the nucleus and cytoplasm.
Anti-Ganglioside Antibodies in New Onset Type 1 Diabetic Patients and High Risk Subjects (1995)

Insulin dependent (type 1) diabetes mellitus appears to be a genetically determined autoimmune disease. Gangliosides have been implicated in type 1 diabetes as antigenic determinants recognized by islet cell antibodies (ICA) and shown to be able to modulate autoimmune phenomena in experimental diabetes. In order to explore in type 1 diabetes the humoral immune reactivity against gangliosides, taking into account their pancreatic localization and molecular characteristics, antibodies to gangliosides GM3, GM2, GM1, GD3, GD1a, GD1b, and GT1b have been investigated in sera from new onset type 1 diabetics and relatives of type 1 diabetic patients with or without insulin (CIAA) and/or islet cell autoantibodies. Using a purposefully designed sensitive ELISA method we found that presence of antibodies directed against the pacreatic disialo-ganglioside GD3 in a significant percentage of newly diagnosed type 1 diabetics (p < 0.001 vs normal controls) but not in CIAA and/or ICA positive relatives of type 1 diabetics. These findings confirm the involvement of gangliosides in autoimmune phenomena related to type 1 diabetes and suggest disialo-ganglioside GD3 as target of a humoral immune response associated with the onset of insulin-dependent diabetes.