gebhart/patrepeval huggingface dataset:
A comparative analysis of the kinetic mechanism and peptide substrate specificity of human and Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (1993)

Human myristoyl-CoA:protein N-myristoyltransferase (hNmt) catalyzes the transfer of myristate from CoA to the amino-terminal Gly residue of a number of cellular proteins involved in signal transduction pathways, to structural and nonstructural proteins encoded by retroviruses, hepadnaviruses, picornaviruses, and reoviruses, as well as to several transforming tyrosine kinases. hNmt has been purified 230-fold from an erythroleukemia cell line. The monomeric enzyme has no associated methionyl aminopeptidase activity. To determine the enzyme's kinetic mechanism, we examined the effect of covariation of subsaturating concentrations of myristoyl-CoA and peptide substrate on initial velocity. Double-reciprocal plots excluded a double displacement (ping-pong) mechanism. Product inhibition studies indicated that CoA was a noncompetitive inhibitor against myristoyl-CoA and a mixed-type inhibitor against peptide substrates. Together these results are consistent with a sequential ordered mechanism where, in a typical catalytic cycle, myristoyl-CoA binds to apoenzyme before peptide followed by release of the CoA and then myristoylpeptide products. This kinetic mechanism is identical to that described for Saccharomyces cerevisiae N-myristoyl-transferase (Nmt1p) and emphasizes the impact that regulation of myristoyl-CoA pool size and accessibility may have in modulating protein N-myristoylation in these two species. Comparative studies of the peptide substrate specificities of hNmt and Nmt1p using a panel of 12 octapeptides revealed distinct differences in their tolerance for amino acid substitutions at positions 3, 4, 7, and 8 of parental peptides derived from the amino-terminal sequences of known N-myristoyl-proteins. This finding contrasts with our recent observation that the acyl-CoA substrate specificities of hNmt and Nmt1p are highly conserved and suggests that these differences in peptide recognition provide an opportunity to develop species-specific enzyme inhibitors.
Universal polymer coatings and their representative biomedical applications (2015)

Universal polymer coatings have excellent potential for biomedical applications, because of their substrate-independent properties and versatile surface functionalization methods.
The Neutral Theory of Molecular Evolution (1983)

Motoo Kimura, as founder of the neutral theory, is uniquely placed to write this book. He first proposed the theory in 1968 to explain the unexpectedly high rate of evolutionary change and very large amount of intraspecific variability at the molecular level that had been uncovered by new techniques in molecular biology. The theory - which asserts that the great majority of evolutionary changes at the molecular level are caused not by Darwinian selection but by random drift of selectively neutral mutants - has caused controversy ever since. This book is the first comprehensive treatment of this subject and the author synthesises a wealth of material - ranging from a historical perspective, through recent molecular discoveries, to sophisticated mathematical arguments - all presented in a most lucid manner.
Perspectives on Chemistry and Therapeutic Applications of Locked Nucleic Acid (LNA) (2007)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPerspectives on Chemistry and Therapeutic Applications of Locked Nucleic Acid (LNA)Harleen Kaur, B. Ravindra Babu, and Souvik MaitiView Author Information Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi 110 007, India, and Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK-5230 Odense M, Denmark Cite this: Chem. Rev. 2007, 107, 11, 4672–4697Publication Date (Web):October 18, 2007Publication History Received18 April 2006Published online18 October 2007Published inissue 1 November 2007https://pubs.acs.org/doi/10.1021/cr050266uhttps://doi.org/10.1021/cr050266uresearch-articleACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views4725Altmetric-Citations250LEARN 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 SUBJECTS:Biopolymers,Genetics,Monomers,Peptides and proteins,Probes Get e-Alerts
A Birefringent and Transparent Electrical Conductor (2008)

Abstract We have developed a range of thin film coatings that are transparent in the visible, electrically conducting, adjustably birefringent and capable of aligning calamitic liquid crystals. The coatings were fabricated from indium tin oxide by oblique or glancing angle deposition, and a wide range of microstructures such as helices, chevrons, uniaxial posts and biaxial slabs were produced. Under many deposition conditions, these structures showed optical transmittance and electrical conductivity comparable to standard indium tin oxide, yet a strong form birefringence (Δ n &gt; 0.07 at 589 nm) was also measured. In addition, many coatings were found to be capable of aligning liquid crystals along a common director, leading us to conclude that the technology may be useful in liquid crystal displays and other lightwave applications.
Role of Extracellular Transaldolase from Bifidobacterium bifidum in Mucin Adhesion and Aggregation (2012)

The ability of bifidobacteria to establish in the intestine of mammals is among the main factors considered to be important for achieving probiotic effects. The role of surface molecules from Bifidobacterium bifidum taxon in mucin adhesion capability and the aggregation phenotype of this bacterial species was analyzed. Adhesion to the human intestinal cell line HT29 was determined for a collection of 12 B. bifidum strains. In four of them-B. bifidum LMG13195, DSM20456, DSM20239, and A8-the involvement of surface-exposed macromolecules in the aggregation phenomenon was determined. The aggregation of B. bifidum A8 and DSM20456 was abolished after treatment with proteinase K, this effect being more pronounced for the strain A8. Furthermore, a mucin binding assay of B. bifidum A8 surface proteins showed a high adhesive capability for its transaldolase (Tal). The localization of this enzyme on the surface of B. bifidum A8 was unequivocally demonstrated by immunogold electron microscopy experiments. The gene encoding Tal from B. bifidum A8 was expressed in Lactococcus lactis, and the protein was purified to homogeneity. The pure protein was able to restore the autoaggregation phenotype of proteinase K-treated B. bifidum A8 cells. A recombinant L. lactis strain, engineered to secrete Tal, displayed a mucin- binding level more than three times higher than the strain not producing the transaldolase. These findings suggest that Tal, when exposed on the cell surface of B. bifidum, could act as an important colonization factor favoring its establishment in the gut.
Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase. (1975)

A function of P in the alternative complement pathway is to prolong the first order decay of the hemolytic sites on EAC43B in a dose-dependent manner. As the number of initial convertase sites is not changed, even when activated properdin (P) increases the t1/2 10-fold or more, P acts to stabilize rather than to uncover additional sites. P binds to EAC43 to generate EAC43P in a reaction that proceeds slightly more rapidly at 15 degrees C than at 0 degrees C, but reaches the same plateau and does not require divalent cations. The presence of P on EAC43P not only stabilizes the convertase subsequently formed on that cell, but, alternatively, permits transfer to convertase sites on other cells with the stability of the recipient intermediate being dependent on the P available for transfer. The capacity of P to bind to C3b and stabilize C3B contrasts with the inhibitory effect of the C3b inactivator on formation of this amplification convertase.
Comparison of Topical Anesthetics and Lubricants Prior to Urethral Catheterization in Males: A Randomized Controlled Trial (2004)

Use of topical lidocaine gel reduces the pain associated with male urethral catheterization in comparison with topical lubricants only.
An unconventional pathway for reduction of CO 2 to methane in CO-grown Methanosarcina acetivorans revealed by proteomics (2006)

Methanosarcina acetivorans produces acetate, formate, and methane when cultured with CO as the growth substrate [Rother M, Metcalf WW (2004) Proc Natl Acad Sci USA 101:], which suggests novel features of CO metabolism. Here we present a genome-wide proteomic approach to identify and quantify proteins differentially abundant in response to growth on CO versus methanol or acetate. The results indicate that oxidation of CO to CO2 supplies electrons for reduction of CO2 to a methyl group by steps and enzymes of the pathway for CO2 reduction determined for other methane-producing species. However, proteomic and quantitative RT-PCR results suggest that reduction of the methyl group to methane involves novel methyltransferases and a coenzyme F420H2:heterodisulfide oxidoreductase system that generates a proton gradient for ATP synthesis not previously described for pathways reducing CO2 to methane. Biochemical assays support a role for the oxidoreductase, and transcriptional mapping identified an unusual operon structure encoding the oxidoreductase. The proteomic results further indicate that acetate is synthesized from the methyl group and CO by a reversal of initial steps in the pathway for conversion of acetate to methane that yields ATP by substrate level phosphorylation. The results indicate that M. acetivorans utilizes a pathway distinct from all known CO2 reduction pathways for methane formation that reflects an adaptation to the marine environment. Finally, the pathway supports the basis for a recently proposed primitive CO-dependent energy-conservation cycle that drove and directed the early evolution of life on Earth.
Quantitative mass spectrometry of DENV-2 RNA-interacting proteins reveals that the DEAD-box RNA helicase DDX6 binds the DB1 and DB2 3’ UTR structures (2011)

Dengue virus (DENV) is a rapidly re-emerging flavivirus that causes dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), diseases for which there are no available therapies or vaccines. The DENV-2 positive-strand RNA genome contains 5' and 3' untranslated regions (UTRs) that have been shown to form secondary structures required for virus replication and interaction with host cell proteins. In order to comprehensively identify host cell factors that bind the DENV-2 UTRs, we performed RNA chromatography, using the DENV-2 5' and 3' UTRs as "bait", combined with quantitative mass spectrometry. We identified several proteins, including DDX6, G3BP1, G3BP2, Caprin1, and USP10, implicated in P body (PB) and stress granule (SG) function, and not previously known to bind DENV RNAs. Indirect immunofluorescence microscopy showed these proteins to colocalize with the DENV replication complex. Moreover, DDX6 knockdown resulted in reduced amounts of infectious particles and viral RNA in tissue culture supernatants following DENV infection. DDX6 interacted with DENV RNA in vivo during infection and in vitro this interaction was mediated by the DB1 and DB2 structures in the 3' UTR, possibly by formation of a pseudoknot structure. Additional experiments demonstrate that, in contrast to DDX6, the SG proteins G3BP1, G3BP2, Caprin1 and USP10 bind to the variable region (VR) in the 3' UTR. These results suggest that the DENV-2 3' UTR is a site for assembly of PB and SG proteins and, for DDX6, assembly on the 3' UTR is required for DENV replication.
A high speed, high capacity homology matrix: zooming through SV40 and polyoma (1982)

We present a new homology matrix program which owes its basic conception to the two-dimensional dot matrices previously described (1,2), but has important improvements and new features. It scores sequence homology over an adjustable range and plots the scores which are above an operator-determined filtration level. Its powerful noise-filtration system, capacity for compression without much loss of information, and speed of execution make this program a valuable tool in the analysis of homologies, internal direct repeats and reverse repeats, including palindromic sequences. The properties of the program are exemplified by analysis of SV40 and polyoma DNA sequences.
The role of membranes in the mechanism of action of the antineoplastic agent adriamycin. Spin-labeling studies with chronically hypoxic and drug-resistant tumor cells. (1983)

Electron spin resonance spectroscopy has been employed to analyze the changes in membrane order parameter in Sarcoma 180 cells under conditions in which an alteration in cellular susceptibility to the chemotherapeutic agent adriamycin is demonstrable. Changes in relative membrane fluidity using the paramagnetic probe 5-doxyl stearic acid were found to be associated with two phenomena which result in an altered cellular response to adriamycin: (a) the presence of an oxygen-deficient environment and (b) the expression of drug resistance. Under hypoxic conditions, in which the susceptibility to the cytotoxic action of adriamycin is increased, a decrease in bulk membrane order parameter was observed. Upon reoxygenation, the membrane fluidity and enhanced susceptibility to adriamycin reverted to control conditions with the same time course. In the case of drug-resistant cells, a progressive decrease in membrane fluidity was also observed which correlated with the degree of resistance to adriamycin. These data suggest that the physical alterations in the membrane reported by the spin label may be functionally linked to biological alterations in sensitivity to adriamycin.
Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats (2019)

Regeneration of human kidneys in animal models would help combat the severe shortage of donors in transplantation therapy. Previously, we demonstrated by interspecific blastocyst complementation between mouse and rats, generation of pluripotent stem cell (PSC)-derived functional pancreas, in apancreatic Pdx1 mutant mice. We, however, were unable to obtain rat PSC-derived kidneys in anephric Sall1 mutant mice, likely due to the poor contribution of rat PSCs to the mouse metanephric mesenchyme, a nephron progenitor. Here, conversely, we show that mouse PSCs can efficiently differentiate into the metanephric mesenchyme in rat, allowing the generation of mouse PSC-derived kidney in anephric Sall1 mutant rat. Glomerular epithelium and renal tubules in the kidneys are entirely composed of mouse PSC-derived cells expressing key functional markers. Importantly, the ureter-bladder junction is normally formed. These data provide proof-of-principle for interspecific blastocyst complementation as a viable approach for kidney generation.
Results of the Treatment of Neurogenic Bladder Dysfunction in Spinal Cord Injury by Sacral Posterior Root Rhizotomy and Anterior Sacral Root Stimulation (1996)

The treatment of neurogenic bladder dysfunction in spinal cord injury by anterior sacral root stimulation with the Finetech-Brindley stimulator in combination with sacral posterior root rhizotomy provides excellent results with limited morbidity.
Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis (2019)

The balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) maintains hematopoietic homeostasis, failure of which can lead to hematopoietic disorder. HSPC fate is controlled by signals from the bone marrow niche resulting in alteration of the stem cell transcription network. Regnase-1, a member of the CCCH zinc finger protein family possessing RNAse activity, mediates post-transcriptional regulatory activity through degradation of target mRNAs. The precise function of Regnase-1 has been explored in inflammation-related cytokine expression but its function in hematopoiesis has not been elucidated. Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA. In addition, we found that dysfunction of Regnase-1 leads to the rapid onset of abnormal hematopoiesis. Thus, our data reveal that Regnase-1-mediated post-transcriptional regulation is required for HSPC maintenance and suggest that it represents a leukemia tumor suppressor.
Quo Vadis Cell Growth and Division? (2016)

SPECIALTY GRAND CHALLENGE article Front. Cell Dev. Biol., 30 August 2016Sec. Cell Growth and Division Volume 4 - 2016 | https://doi.org/10.3389/fcell.2016.00095
Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells (2006)

Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC, but a longer culture period and higher proliferation capacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.
An optimized 3D-stacked memory architecture by exploiting excessive, high-density TSV bandwidth (2010)

Memory bandwidth has become a major performance bottleneck as more and more cores are integrated onto a single die, demanding more and more data from the system memory. Several prior studies have demonstrated that this memory bandwidth problem can be addressed by employing a 3D-stacked memory architecture, which provides a wide, high frequency memory-bus interface. Although previous 3D proposals already provide as much bandwidth as a traditional L2 cache can consume, the dense through-silicon-vias (TSVs) of 3D chip stacks can provide still more bandwidth. In this paper, we contest that we need to re-architect our memory hierarchy, including the L2 cache and DRAM interface, so that it can take full advantage of this massive bandwidth. Our technique, SMART-3D, is a new 3D-stacked memory architecture with a vertical L2 fetch/write-back network using a large array of TSVs. Simply stated, we leverage the TSV bandwidth to hide latency behind very large data transfers. We analyze the design trade-offs for the DRAM arrays, careful enough to avoid compromising the DRAM density because of TSV placement. Moreover, we propose an efficient mechanism to manage the false sharing problem when implementing SMART-3D in a multi-socket system. For single-threaded memory-intensive applications, the SMART-3D architecture achieves speedups from 1.53 to 2.14 over planar designs and from 1.27 to 1.72 over prior 3D designs. We achieve similar speedups for multi-program and multi-threaded workloads on multi-core and multi-socket processors. Furthermore, SMART-3D can even lower the energy consumption in the L2 cache and 3D DRAM for it reduces the total number of row buffer misses.
Body iron stores and risk of cancer (1994)

A high level of available tissue iron may increase the risk of cancer through its contribution to the production of free oxygen radicals. Serum iron, total iron-binding capacity (TIBC) and transferrin saturation levels were studied for their prediction of different cancers in a cohort of 41,276 men and women aged 20-74 years and initially free from cancer. During a mean follow-up of 14 years, 2,469 primary cancer cases were diagnosed. Excess risks of colorectal and lung cancers were found in subjects with transferrin saturation level exceeding 60%. The relative risks, adjusted for age, sex and smoking, were 3.04 for colorectal cancer and 1.51 for lung cancer, in comparison with subjects having lower levels. The risk of lung cancer was inversely related to serum TIBC, with a relative risk between the highest and lowest quartiles of 0.69 for men and 0.19 for women. For the risk of stomach cancer, we detected inverse relationships with serum iron and with transferrin saturation and a positive relationship with TIBC, but these associations weakened when the cancer cases occurring during the 5 first years of follow-up were excluded. High iron stores may increase the risk of colorectal cancer, whereas low iron stores may be an early sign of occult stomach cancer.
Elucidation of structural requirements on plasminogen activator inhibitor 1 for binding to heparin. (1992)

Plasminogen activator inhibitor 1 (PAI-1), a member of the serpin superfamily of proteins, has been demonstrated previously to interact functionally with the glycosaminoglycan heparin (Ehrlich, H.J., Keijer, J., Preissner, K. T., Klein Gebbink, R., and Pannekoek, H. (1991) Biochemistry 30, 1021-1028). Heparin specifically enhances the rate of association between PAI-1 and thrombin about 2 orders of magnitude, whereas no effect is detected with other serine proteases (e.g. factor Xa). For the heparin-dependent serpins antithrombin III and heparin cofactor II, basic amino acid residues in and around the helix D subdomain were proposed to be involved in the binding of glycosaminoglycans. Here we employed site-directed mutagenesis of full-length PAI-1 cDNA to identify the amino acid residues that mediate heparin binding. To that end, 15 single-point mutants of PAI-1, each having individual arginyl, lysyl, or histidyl residues replaced by a neutral (alanyl) residue ("ala-scan"), and one double mutant were constructed, expressed in Escherichia coli, and purified to apparent homogeneity. The purified biologically active proteins were subjected to the following analyses: (i) heparin-dependent inhibition of thrombin; (ii) heparin-dependent formation of sodium dodecyl sulfate-stable complexes with thrombin; and (iii) binding to and elution from heparin-Sepharose. Based on the data presented, we propose that the amino acid residues Lys65, Lys69, Arg76, Lys80, and Lys88 constitute major determinants for heparin binding of PAI-1. These residues are located in and around the helix D domain and are conserved in the other heparin-dependent thrombin inhibitors, antithrombin III and heparin cofactor II.
Qualification of the Hemagglutination Inhibition Assay in Support of Pandemic Influenza Vaccine Licensure (2009)

Continued outbreaks of highly pathogenic avian influenza over the past decade have spurred global efforts to develop antivirals and vaccines. As part of vaccine development, standard methods are needed for determining serum antibody titers in response to vaccination. Hemagglutination inhibition (HAI) assays are appropriate for assessing the immunogenicity of pandemic influenza vaccines in support of license approval. We demonstrate that a rigorous qualification of the HAI assay for H5N1 influenza virus, evaluating for precision, intermediate precision, linearity, range, specificity, and robustness, satisfies the intent of regulatory guidance for assay validation despite the lack of availability of specific reference standard antigens and antisera.