gebhart/patrepeval huggingface dataset:
A BASIC microcomputer program for prediction of B and T cell epitopes in proteins (1990)

A BASIC microcomputer program (EPIPLOT) has been developed for predicting B and T cell antigenic sites in proteins from their primary structures. The program calculates and plots flexibility, hydrophilicity and antigenicity profiles using 13 different scales, chosen as those yielding the best predictions on proteins whose antigenic structures are known. T cell epitope prediction is based on published algorithms focused on amphiphilic structures and characteristic sequence patterns. The advantages of joint predictions in locating T cell antigenic sites are also discussed.
Wnt7a treatment ameliorates muscular dystrophy (2012)

Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder of childhood marked by progressive debilitating muscle weakness and wasting, and ultimately death in the second or third decade of life. Wnt7a signaling through its receptor Fzd7 accelerates and augments regeneration by stimulating satellite stem cell expansion through the planar cell polarity pathway, as well as myofiber hypertrophy through the AKT/mammalian target of rapamycin (mTOR) anabolic pathway. We investigated the therapeutic potential of the secreted factor Wnt7a for focal treatment of dystrophic DMD muscles using the mdx mouse model, and found that Wnt7a treatment efficiently induced satellite cell expansion and myofiber hypertrophy in treated mucles in mdx mice. Importantly, Wnt7a treatment resulted in a significant increase in muscle strength, as determined by generation of specific force. Furthermore, Wnt7a reduced the level of contractile damage, likely by inducing a shift in fiber type toward slow-twitch. Finally, we found that Wnt7a similarly induced myotube hypertrophy and a shift in fiber type toward slow-twitch in human primary myotubes. Taken together, our findings suggest that Wnt7a is a promising candidate for development as an ameliorative treatment for DMD.
The Structure−Activity Relationship between Peroxisome Proliferator-Activated Receptor γ Agonism and the Antihyperglycemic Activity of Thiazolidinediones (1996)

ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTThe Structure−Activity Relationship between Peroxisome Proliferator-Activated Receptor γ Agonism and the Antihyperglycemic Activity of ThiazolidinedionesTimothy M. Willson, Jeffery E. Cobb, David J. Cowan, Robert W. Wiethe, Itzela D. Correa, Shimoga R. Prakash, Kelli D. Beck, Linda B. Moore, Steven A. Kliewer, and Jürgen M. LehmannView Author Information Glaxo Wellcome Research and Development, Five Moore Drive, Research Triangle Park, North Carolina 27709 Cite this: J. Med. Chem. 1996, 39, 3, 665–668Publication Date (Web):February 2, 1996Publication History Received29 November 1995Published online2 February 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jm950395ahttps://doi.org/10.1021/jm950395arapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views3231Altmetric-Citations539LEARN 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:Carbohydrates,Ligands,Peptides and proteins,Receptors,Rodent models Get e-Alerts
Diphencyprone and topical tacrolimus as two topical immunotherapeutic modalities. Are they effective in the treatment of alopecia areata among Egyptian patients? A study using CD4, CD8 and MHC II as markers (2010)

DCPC is one of the most accepted therapeutic modalities in the treatment of AA, with a favourable prognosis among patchy hair loss. MHC II expression was the one correlating with clinical response. Tacrolimus, though beneficial in other dermatoses, could not be considered effective in the treatment of AA.
Characterization of the DNA-binding properties of the myeloid zinc finger protein MZF1: two independent DNA-binding domains recognize two DNA consensus sequences with a common G-rich core. (1994)

The myeloid zinc finger gene 1, MZF1, encodes a transcription factor which is expressed in hematopoietic progenitor cells that are committed to myeloid lineage differentiation. MZF1 contains 13 C2H2 zinc fingers arranged in two domains which are separated by a short glycine- and proline-rich sequence. The first domain consists of zinc fingers 1 to 4, and the second domain is formed by zinc fingers 5 to 13. We have determined that both sets of zinc finger domains bind DNA. Purified, recombinant MZF1 proteins containing either the first set of zinc fingers or the second set were prepared and used to affinity select DNA sequences from a library of degenerate oligonucleotides by using successive rounds of gel shift followed by PCR amplification. Surprisingly, both DNA-binding domains of MZF1 selected similar DNA-binding consensus sequences containing a core of four or five guanine residues, reminiscent of an NF-kappa B half-site: 1-4, 5'-AGTGGGGA-3'; 5-13, 5'-CGGGnGAGGGGGAA-3'. The full-length MZF1 protein containing both sets of zinc finger DNA-binding domains recognizes synthetic oligonucleotides containing either the 1-4 or 5-13 consensus binding sites in gel shift assays. Thus, we have identified the core DNA consensus binding sites for each of the two DNA-binding domains of a myeloid-specific zinc finger transcription factor. Identification of these DNA-binding sites will allow us to identify target genes regulated by MZF1 and to assess the role of MZF1 as a transcriptional regulator of hematopoiesis.
Modulation of promiscuous T cell receptor recognition by mutagenesis of CDR2 residues. (1996)

The T cell receptor (TCR) recognizes a ligand composed of a major histocompatibility complex (MHC) molecule and a peptide antigen. Prior studies of murine T cell clones have demonstrated that residues in the CDR3 region of TCR interact with amino acids in the peptide during MHC-restricted antigen recognition. However, the questions of whether direct TCR MHC contacts are made and where such contact sites might map in the TCR have not been resolved. In this study, we have taken advantage of the promiscuous recognition of a peptide from influenza virus (HA 307-319) by human T cell clones to map sites in the TCR that mediate differences in human leukocyte antigen-D related (HLA-DR) restriction in the presence of a common peptide antigen. Site-specific mutagenesis of cloned TCR genes and transfection into Jurkat cells were used to demonstrate that single amino acid substitutions in CDR2 of the TCR-alpha chain controlled whether a T cell was restricted by the product of a single DR allele (DR7) or would respond to the HA 307-319 peptide when presented by the products of one of several different DR alleles (DR1, DR4, DR5, or DR7). Because the relevant DR alleles are defined by polymorphism in the DR-beta chain, these results also suggest a rotational orientation for recognition in which TCR-alpha interacts with DR beta.
An accurate, precise, and affordable light emitting diode spectrophotometer for drinking water and other testing with limited resources (2020)

Spectrophotometers are commonly used to measure the concentrations of a wide variety of analytes in drinking water and other matrixes; however, many laboratories with limited resources cannot afford to buy these very useful instruments. To meet this need, an accurate, precise, and affordable light emitting diode (LED) spectrophotometer was designed and built using best engineering practices and modern circuit design. The cost and performance of this LED spectrophotometer was compared against 4 common commercial spectrophotometers. More specifically, the performance of these spectrophotometers was evaluated from the upper limits of linear range, upper limits of operational range, calibration sensitivities, R2 values, precisions of standards, estimated limits of detection, and percent calibration check standard recoveries for the determinations of iron (Fe), manganese (Mn), and fluoride (F-) in drinking water. This evaluation was done in the United States (U.S.) and India. Our LED spectrophotometer costs $63 United States Dollars (USD) for parts. The 4 commercial spectrophotometers ranged in cost from $2,424 to $7,644 USD. There are no practical differences in the upper limits of linear range, upper limits of operational range, R2 values, precisions of standards, and estimated limits of detection for our LED spectrophotometer and the 4 commercial spectrophotometers. For 2 of the 3 analytes, there is a practical difference in the calibration sensitivities our LED spectrophotometer and the 4 commercial spectrophotometers. More specifically, the calibration sensitivities for Mn and F- using our LED spectrophotometer were 65.2% and 67.0% of those using the 4 commercial spectrophotometers, respectively. In conclusion, this paper describes the design, use, and performance of an accurate, precise, and extremely affordable LED spectrophotometer for drinking water and other testing with limited resources.
Femtosecond Clocking of the Chemical Bond (1988)

When a chemical bond is broken in a direct dissociation reaction, the process is so rapid that it has generally been considered instantaneous and thus unmeasurable. However, the bond does persist for times on the order of 10(-13) seconds after the photon has been absorbed. Femtosecond (10(-15) second) laser techniques can be used to directly clock this process, which describes the dynamics of the chemical bond. The time required to break the chemical bond in an elementary reaction has been measured and the characteristic repulsion length for the potential governing fragment separation has been obtained.
Dna2 nuclease-helicase structure, mechanism and regulation by Rpa (2015)

The Dna2 nuclease-helicase maintains genomic integrity by processing DNA double-strand breaks, Okazaki fragments and stalled replication forks. Dna2 requires ssDNA ends, and is dependent on the ssDNA-binding protein Rpa, which controls cleavage polarity. Here we present the 2.3 Å structure of intact mouse Dna2 bound to a 15-nucleotide ssDNA. The nuclease active site is embedded in a long, narrow tunnel through which the DNA has to thread. The helicase domain is required for DNA binding but not threading. We also present the structure of a flexibly-tethered Dna2-Rpa interaction that recruits Dna2 to Rpa-coated DNA. We establish that a second Dna2-Rpa interaction is mutually exclusive with Rpa-DNA interactions and mediates the displacement of Rpa from ssDNA. This interaction occurs at the nuclease tunnel entrance and the 5' end of the Rpa-DNA complex. Hence, it only displaces Rpa from the 5' but not 3' end, explaining how Rpa regulates cleavage polarity.
Structural Studies of Mutants of T4 Lysozyme That Alter Hydrophobic Stabilization (1989)

Multiple replacements at amino acid position 3 of bacteriophage T4 lyriozyme have shown that the conformational stability of the protein is directly governed by the hydrophobicity of the residue substituted (Matsumura, M., Becktel, W. J., and Matthews, B. W. (1988) Nature 334,[406][407][408][409][410].Of the 13 mutant lysozymes made by site-directed mutagenesis, two variants, one with valine (I3V) and the other with tyrosine (I3Y), were crystallkzed and their structures solved.In this report we Cescribe the crystal structures of these variants at 1.7 A res(o1ution.While the structure of the 13V mutant is essentially the same as that of wild-type lysozyme, the 13Y mutant has substantial changes in its structure.The most significant of these are that the side chain of the tyrosine is not accommodated within the interior of the protein and the aminq-terminal polypeptide (residues 1-!3) moves 0.6-1.1 A relative to the wild-type structure.Using coordinates based on the wild-type and available mutant structures, solvent accessible surface area of residue 3 as well as the adjacent 9 residues in the foldled form were calculated.The free energy of stabilization based on the transfer of these residues from a fully extended form to the interior to the folded protein was found to correlate well with the protein stability determined by thermodynamic analysis.The enhanced thermostability of the variant Ile-3 + Leu, relative to wild-type lysozyme, can also be rationalized by surface-area calculations based on a model-built structure.Noncrystallization of most lysozyme variants at position 3 appears to be due to disruption of intermolecular contacts in the crystal.The Ile-3 + Val variant is closely isomorphous with wild-type and maintains the same crystal contacts.In the Ile-3 + Tyr variant, however, a new set of contacts is made in which direct protein-protein hydrogen bonds are replaced by protein-water-protein hydrogen bonds as well as a novel hydrogen bond involving the phenolic hydroxyl of the substituted tyrosine.The noncovalent interactions that determine the folding and stability of proteins have been studied extensively yet the quantitative understanding of their physical basis is still not well understood.Mut,ant proteins which result from single amino acid substitutions, in combination with x-ray crystallography, are particularly useful in addressing this problem area (1-11).
Association of gelsolin with actin filaments and cell membranes of macrophages and platelets. (1989)

Recent evidence that polyphosphoinositides regulate the function of the actin-modulating protein gelsolin in vitro raises the possibility that gelsolin interacts with cell membranes. This paper reports ultrastructural immunohistochemical data revealing that gelsolin molecules localize with plasma and intracellular membranes, including rough endoplasmic reticulum, cortical vesicles and mitochondria of macrophages, and blood platelets. Anti-gelsolin gold also labeled the surface and interior of secondary lysosomes presumably representing plasma gelsolin ingested by these cells from the lung surface by endocytosis. Gelsolin molecules, visualized with colloidal gold in replicas of the cytoplasmic side of the substrate-adherent plasma membrane of mechanically unroofed and rapidly frozen and freeze-dried macrophages, associated with the ends of short actin filaments sitting on the cytoplasmic membrane surface. A generalized distribution of gelsolin molecules in thin sections of resting platelets rapidly became peripheral, and plasmalemma association increased following thrombin stimulation. At later times the distribution reverted to the cytoplasmic distribution of resting cells. These findings provide the first evidence for gelsolin binding to actin filament ends in cells and indicate that gelsolin functions in both cytoplasmic and membrane domains.
Refinement of the influenza virus hemagglutinin by simulated annealing (1990)

We have applied the method of simulated annealing to the refinement of the 3 A resolution crystal structure of the influenza virus hemagglutinin glycoprotein, using the program X-PLOR. Two different methods were introduced into X-PLOR to treat the non-crystallographic symmetry present in this and in other crystal structures. In the first, only the unique protomer atoms are refined; by application of the non-crystallographic symmetry operators to the protomer atoms, the X-ray structure factor derivatives are effectively averaged, and a non-bonded energy term models the interactions of the protomer with its neighbors in the oligomer without explicit refinement of the other protomers in the crystallographic asymmetric unit. In the second method, the entire asymmetric unit is refined, but an effective energy term is added to the empirical energy that restrains symmetry-related atomic positions to their average values after least-squares superposition. Several other modifications and additions were made to previously published X-PLOR protocols, including weighting of the X-ray terms, maintenance of the temperature of the molecular dynamics simulation, treatment of charged groups, changes in the values of certain empirical energy parameters, and the use of N-linked carbohydrate empirical energy parameters. The hemagglutinin refinement proceeded in several stages. An initial round of simulated annealing of the monomer was followed by rigid-body refinement of the 3-fold non-crystallographic symmetry axis position and a second round of monomer refinement. A third round was performed on the trimer using non-crystallographic symmetry restraints in all regions except those in lattice contacts showing obvious derivations from 3-fold symmetry. The refinement was completed with several rounds of conventional positional and isotropic temperature factor refinement needed to correct bad model geometry introduced by high-temperature molecular dynamics in regions of weak electron density. This structure was then used as the basis for refinement of three crystallographically isomorphous hemagglutinin structures, including complexes with the influenza virus receptor, sialic acid. Model geometry comparable to well-refined high-resolution structures was obtained with relatively little manual intervention, demonstrating the ability of simulated annealing refinement to produce highly idealized structures at moderate resolution.
A Novel Long-Acting Human Growth Hormone Fusion Protein (VRS-317): Enhanced In Vivo Potency and Half-Life (2012)

A novel recombinant human growth hormone (rhGH) fusion protein (VRS-317) was designed to minimize receptor-mediated clearance through a reduction in receptor binding without mutations to rhGH by genetically fusing with XTEN amino acid sequences to the N-terminus and the C-terminus of the native hGH sequence. Although in vitro potency of VRS-317 was reduced approximately 12-fold compared with rhGH, in vivo potency was increased because of the greatly prolonged exposure to the target tissues and organs. VRS-317 was threefold more potent than daily rhGH in hypophysectomized rats and fivefold more potent than daily rhGH in juvenile monkeys. In juvenile monkeys, a monthly dose of 1.4 mg/kg VRS-317 (equivalent to 0.26 mg/kg rhGH) caused a sustained pharmacodynamic response for 1 month equivalent to 0.05 mg/kg/day rhGH (1.4 mg/kg rhGH total over 28 days). In monkeys, VRS-317, having a terminal elimination half-life of approximately 110 h, was rapidly and near-completely absorbed, and was well tolerated with no observed adverse effects after every alternate week subcutaneous dosing for 14 weeks. VRS-317 also did not cause lipoatrophy in pig and monkey studies. VRS-317 is currently being studied in GH-deficient patients to confirm the observations in these animal studies.
The cellular location of a foreign B cell epitope expressed by recombinant bacteria determines its T cell-independent or T cell-dependent characteristics (1991)

We have targeted two foreign B cell antigenic determinants to different locations in the Escherichia coli cell to examine what effect this had on antibody responses elicited by the recombinant bacteria. The two epitopes were the 132-145 peptide from the PreS2 region of hepatitis B virus and the C3 neutralization epitope of poliovirus type 1. They were each expressed in two forms either on the surface, as part of the outer-membrane protein LamB, or soluble in the periplasm, as part of the periplasmic protein MalE. When live bacteria expressing the foreign epitope at the cell surface were used for immunization of mice, they induced T cell-independent antibody responses characterized by a rapid induction of IgM and IgG antibodies. In contrast, when the same foreign epitope was inserted into the MalE protein, the antibody response was only detectable after 3 wk, belonged only to the IgG class and was strictly T cell dependent. This study has therefore identified two major pathways by which epitopes expressed by bacterial cells can stimulate specific antibody responses. The first pathway is mediated by direct activation of B cells by bacterial cell-surface Ag and does not require T cell help. The second pathway is T cell dependent and concerns Ag that can be released from the bacteria in a soluble form. We have also studied the effect of the exact position of the B cell antigenic determinant within the LamB protein and with respect to the outer membrane by comparing the immunogenicity of the PreS epitope inserted at three different permissive sites of LamB. The data indicated that to obtain an antibody response with intact bacteria, the epitope must be protruding sufficiently from the outside of the outer membrane. In contrast, when semipurified hybrid proteins were used as immunogen, the exact position of the B cell antigenic determinant within solubilized LamB protein does not influence its immunogenicity.
A Malaria Vaccine Candidate Based on a Hepatitis B Virus Core Platform (2002)

These characteristics suggest that V12.PF3.1 represents an efficient and economical P. falciparum vaccine candidate for use separately or in combination with other formulations.
Intergeneric transfer and recombination of the 6-phosphogluconate dehydrogenase gene (gnd) in enteric bacteria. (1994)

The gnd gene, encoding 6-phosphogluconate dehydrogenase (EC 1.1.1.44), was sequenced in 87 strains of 15 species assigned to five nominal genera of the Enterobacteriaceae, including 36 isolates of Salmonella enterica and 32 strains of Escherichia coli. In S. enterica, the effective (realized) rate of recombination of horizontally transferred gnd sequences is only moderately higher than the rates for other chromosomal housekeeping genes. In contrast, recombination at gnd has occurred with such high frequency in Escherichia coli that the indicated evolutionary relationships among strains are not congruent with those estimated by sequence analysis of other genes and by multilocus enzyme electrophoresis. E. coli and S. enterica apparently have not exchanged gnd sequences, but those of several strains of E. coli have been imported from species of Citrobacter and Klebsiella. The relatively frequent exchange of gnd within and among taxonomic groups of the Enterobacteriaceae, compared with other housekeeping genes, apparently results from its close linkage with genes that are subject to diversifying selection, including those of the rfb region determining the structure of the O antigen polysaccharide.