gebhart/patrepeval huggingface dataset:
Effect of resistance exercise on free radical production (1998)

The purposes of this investigation were to see whether free radical production changed with high intensity resistance exercise and, secondly, to see whether vitamin E supplementation would have any effect on free radical formation or variables associated with muscle membrane disruption. Twelve recreationally weight-trained males were divided into two groups. The supplement group (S) received 1200 IUs of vitamin E once a day (3 x 400 IU x d[-1]) for a period of 2 wk. The placebo group (P) received cellulose-based placebo pills once a day for the same period of time. Creatine kinase activity was significantly elevated between preexercise and immediately postexercise, 6 h postexercise, and 24 h postexercise for both groups. The placebo group also had a significant increase in creatine kinase activity at 48 h postexercise. There was a significant difference in creatine kinase activity between the groups at 24 h after exercise. Plasma malondialdehyde significantly increased from preexercise levels for the P group at 6 and 24 h postexercise. Plasma malondialdehyde concentrations significantly increased in the S group between preexercise and immediately postexercise levels. This study indicates that high intensity resistance exercise increases free radical production and that vitamin E supplementation may decrease muscle membrane disruption.
Activation of Protein Kinase C ϵ Inhibits the Two-pore Domain K+ Channel, TASK-1, Inducing Repolarization Abnormalities in Cardiac Ventricular Myocytes (2004)

Activation of the platelet-activating factor (PAF) receptor leads to a decrease in outward current in murine ventricular myocytes by inhibiting the TASK-1 channel. TASK-1 carries a background or "leak" current and is a member of the two-pore domain potassium channel family. Its inhibition is sufficient to delay repolarization, causing prolongation of the action potential duration, and in some cases, early after depolarizations. We set out to determine the cellular mechanisms that control regulation of TASK-1 by PAF. Inhibition of TASK-1 via activation of the PAF receptor is protein kinase C (PKC)-dependent. Using isoform-specific PKC inhibitor or activator peptides in patch clamp experiments, we now demonstrate that activation of PKCepsilon is both necessary and sufficient to regulate murine TASK-1 current in a heterologous expression system and to induce repolarization abnormalities in isolated myocytes. Furthermore, site-directed mutagenesis studies have identified threonine 381, in the C-terminal tail of murine TASK-1, as a critical residue in this regulation.
Molecular and crystal structures of ecteinascidins: potent antitumor compounds from the Caribbean tunicate Ecteinascidia turbinata. (1993)

Some members of marine alkaloid ecteinascidins (Et's), isolated from the Caribbean tunicate Ecteinascidia turbinata, exhibit potent anticancer activity. The three dimensional structures of the N12-formyl derivative of Et729 1a and the natural N12-oxide of Et743 2 have been determined by x-ray crystallography at 0.9 A resolution. Compounds 1a and 2 crystallize in the space groups P2(1)2(1)2(1) (a = 23.214(9) A, b = 28.541(10) A and c = 13.303(9) A) and P2(1) (a = 11.720(5) A, b = 13.230(4) A, c = 28.557(5) A, beta = 90.22(2) degrees), respectively. Their crystal structures have been solved by the Patterson search method, which located the sulfur atoms permitting the phase extension. The final crystallographic R-factors are 0.059 and 0.069 for 1a and 2, respectively. There are two independent molecules, associated as a dimer, in the asymmetric unit of crystals of both 1a and 2. The structure determination allows an unequivocal assignment of the relative configuration of all the chiral centers. Assuming that ecteinascidins and safracin C (whose absolute configuration is known) have the same absolute configuration at C1 position, then the absolute configurations of various chiral positions in Ets are C1(R), N2(R), C3(R), C4(R), C11(R), C13(S), C21(S) and C22(R), respectively. The four independent Et molecules adopt two conformations in which the position of ring C relative to rings A & B is different. The molecules have a compact shape and they are conformationally strained due to a severe van der Waals clash between the sulfur atom and the aromatic ring A. By analogy to the related saframycin, the potent biological activity of Et's may be associated with their ability to form a covalent adduct to DNA using the reactive carbinolamine group. The covalent binding interaction between the Et and the N2 of guanine in the minor groove of the DNA double helix has been studied by computer modelling which suggests that rings A and B "stack" against the DNA backbone. While the bulky drug molecule makes numerous contacts with DNA, it does not significantly distort the conformation of the DNA double helix.
`Florida Slobolt M68': A Spring Celery Cultivar for Florida (1993)

Celery (Apium graveolens L.) is grown as an annual leafy vegetable crop with a biennial reproductive cycle. In southern Florida, celery production is year-round: seeding begins in June and continues through January, and harvest is from November to the middle of the following June. The celery production season is divided into four production periods: late autumn, winter, spring bolting, and spring postbolting. Each production period requires separately adapted cultivars. The celery crop harvested during the spring bolting season is seeded in November and December, transplanted to the field in February and March, and harvested in April and early May, when the weather is cool and dry and daylength is increasing. A major constraint in the April to May harvest period is premature bolting induced by prolonged suboptimal temperatures that vernalize the crop early in the production cycle. Premature bolting results in seed-stem elongation, which, combined with other changes in horticultural quality, can force an early harvest and result in lower yields, lower grade sizes, or stalk rejection. Floral induction and associated regenerative processes result mainly from vernalization experienced in December and January. In contrast, warmer weather patterns and more frequent rainfall in April and
Inflammatory Cytokines and Postmyocardial Infarction Remodeling (2004)

Inflammatory response and cytokine elaboration are particularly active after myocardial infarction and contribute to cardiac remodeling and eventual host outcome. The triggers of cytokine release in the acute postinfarction period include mechanical deformation, ischemic stimulus, reactive oxygen species (ROS), and cytokine self-amplification pathways. Acutely, the elaboration of tumor necrosis factor, IL-1 and IL-6, transforming growth factor families of cytokines, contribute to survival or deaths of myocytes, modulation of cardiac contractility, alterations of vascular endothelium, and recruitment of additional circulating cells of inflammation to the injured myocardium. This leads to further local oxidative stress and remodeling but also initiates the processes of wound healing. Chronically, sustained presence of cytokines leads to myocyte phenotype transition and activation of matrix metalloproteinases that modifies interstitial matrix, augmenting further the remodeling process. This in turn alters the local collagen composition and also the integrins that constitute the interface between myocytes and the matrix. These processes ultimately, when favorable, pave the way for angiogenesis and cellular regeneration. Thus, the insightful modulation of cytokines through current and future therapies could promote improved healing and cardiac remodeling postmyocardial infarction.
The role of template-primer in protection of reverse transcriptase from thermal inactivation (2002)

We compared the thermal stabilities of wild-type recombinant avian myeloblastosis virus (AMV) and Moloney murine leukemia virus (M-MLV) reverse transcriptase (RT) with those of mutants of the recombinant enzymes lacking RNase H activity. They differed in resistance to thermal inactivation at elevated temperatures in the presence of an RNA/DNA template-primer. RNase H-minus RTs retained the ability to efficiently synthesize cDNA at much higher temperatures. We show that the structure of the template-primer has a critical bearing on protection of RT from thermal inactivation. RT RNase H activity rapidly alters the structure of the template-primer to forms less tightly bound by RT and thus less able to protect the enzyme at elevated temperatures. We also found that when comparing wild-type or mutant AMV RT with the respective M-MLV RT, the avian enzymes retained more DNA synthetic activity at elevated temperatures than murine RTs. Enzyme, template-primer interaction again played the most significant role in producing these differences. AMV RT binds much tighter to template- primer and has a much greater tendency to remain bound during cDNA synthesis than M-MLV RT and therefore is better protected from heat inactivation.
Inhibition of the multicatalytic proteinase (proteasome) by 4‐hydroxy‐2‐nonenal cross‐linked protein (1997)

Oxidative modification of glucose-6-phosphate dehydrogenase (Glu-6-PDH), as observed for other proteins, increases the susceptibility of the protein to degradation by the multicatalytic proteinase/proteasome (MCP). Oxidized Glu-6-PDH is, however, more prone to cross-linking reactions by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE), processes which render the protein resistant to proteolysis. In addition, HNE cross-linked protein inhibits the degradation of oxidatively modified glutamine synthetase by the MCP. In contrast to oxidized Glu-6-PDH, which inhibits the proteolysis of GS in a competitive manner, HNE cross-linked protein acts as a noncompetitive inhibitor. As judged by binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, a common structural feature of both macromolecular substrates and inhibitors of the MCP is an increased accessibility of hydrophobic regions on the protein.
Role of Akt Signaling in Mitochondrial Survival Pathway Triggered by Hypoxic Preconditioning (2004)

Our data demonstrated that in adult cardiomyocytes, the antiapoptotic effect of PC against H/R requires Akt signaling leading to phosphorylation of BAD, inhibition of cytochrome c release, and prevention of caspase activation.
Expression of Plasmodium falciparum blood-stage antigens in Escherichia coli: detection with antibodies from immune humans. (1983)

Many proteins produced by blood stages of the malaria parasite Plasmodium falciparum are natural immunogens in man. As an approach to determining which of these are relevant to protective immunity we have constructed an expression library of P. falciparum cDNA sequences, cloned in Escherichia coli. The cDNA sequences were inserted into the beta-galactosidase gene of an ampicillin-resistant derivative of the temperature-sensitive lysogenic bacteriophage lambda gt11. About 5% of the resulting clones expressed P. falciparum sequences as polypeptides fused to beta-galactosidase. We have identified many clones that express P. falciparum antigens by immunological screening in situ with antibodies from immune human sera that inhibit P. falciparum growth in vitro. The antigen-positive clones contain P. falciparum cDNA sequences, as determined by hybridization. Some express polypeptides that are larger than beta-galactosidase and react both with antibodies to beta-galactosidase and with antibodies from humans immune to P. falciparum. The cloned P. falciparum antigens should facilitate new approaches to the identification of potential vaccine molecules.
Photopheresis therapy of cutaneous T-cell lymphoma: the Yale-New Haven Hospital experience. (1990)

Over the past two years, the photopheresis treatment program at Yale-New Haven Hospital has treated 32 patients with cutaneous T-cell lymphoma. There were 19 erythrodermic patients who had photopheresis as their first systemic therapy. Five of these cleared 75 percent of their skin and the majority of erythrodermics achieved an improved quality of life. Those with best responses were treated earlier in the course of their disease and had more normal proportions of CD4 and CD8 subsets when compared to patients with poor responses. In addition, patients with tumor stage disease and those patients in relapse after intensive radio- and chemotherapy were treated with photopheresis. These results demonstrate that photopheresis has a role in the management of cutaneous T-cell lymphoma.
Site-Specific Proteolysis of Fusion Proteins (1990)

The use of gene fusions has greatly facilitated the expression and subsequent purification of heterologous proteins in E. coli (reviewed in 1-2. Uhlén, M.; Moks, T. Methods Enzymol., in press). A commonly used arrangement (C-terminal fusions) is one in which the gene encoding the protein of interest is fused to the 3′ end of a gene which codes for a highly expressed protein (Figure 1). This configuration is attractive because the signals which direct transcription and translation are located at the 5′ end of the gene and will function efficiently in the presence of a variety of different fusions to the 3′ end of the gene. In addition to facilitating expression, the N-terminus of such fusion (hybrid) proteins is often chosen as an "affinity handle": a polypeptide with a high affinity for a particular ligand. At least a dozen different affinity handles have been used in the purification of fusion
Molecular Modeling of Proteins: A Strategy for Energy Minimization by Molecular Mechanics in the AMBER Force Field (1991)

Energy minimization is an important step in molecular modeling of proteins. In this study, we sought to develop a minimization strategy which would give the best final structures with the shortest computer time in the AMBER force field. In the all-atom model, we performed energy minimization of the melittin (mostly alpha-helical) and cardiotoxin (mostly beta-sheet and beta-turns) crystal structures by both constrained and unconstrained pathways. In the constrained path, which has been recommended in the energy minimization of proteins, hydrogens were relaxed first, followed by the side chains of amino acid residues, and finally the whole molecule. Despite the logic of this approach, however, the structures minimized by the unconstrained path fit the experimental structures better than those minimized by constrained paths. Moreover, the unconstrained path saved considerable computer time. We also compared the effects of the steepest descents and conjugate gradients algorithms in energy minimization. Previously, steepest descents has been used in the initial stages of minimization and conjugate gradients in the final stages of minimization. We therefore studied the effect on the final structure of performing an initial minimization by steepest descents. The structures minimized by conjugate gradients alone resembled the structures minimized initially by the steepest descents and subsequently by the conjugate gradients algorithms. Thus an initial minimization using steepest descents is wasteful and unnecessary, especially when starting from the crystal structure. Based on these results, we propose the use of an unconstrained path and conjugate gradients for energy minimization of proteins. This procedure results in low energy structures closer to the experimental structures, and saves about 70-80% of computer time. This procedure was applied in building models of lysozyme mutants. The crystal structure of native T4 lysozyme was mutated to three different mutants and the structures were minimized. The minimized structures closely fit the crystal structures of the respective mutants (less than 0.3 A root-mean-square, RMS, deviation in the position of all heavy atoms). These results confirm the efficiency of the proposed minimization strategy in modeling closely related homologs. To determine the reliability of the united atom approximation, we also performed all of the above minimizations with united atom models. This approximation gave structures with similar but slightly higher RMS deviations than the all-atom model, but gave further savings of 60-70% in computer time. However, we feel further investigation is essential to determine the reliability of this approximation.(ABSTRACT TRUNCATED AT 400 WORDS)
In Silico Prediction of Cytochrome P450 2D6 and 3A4 Inhibition Using Gaussian Kernel Weightedk-Nearest Neighbor and Extended Connectivity Fingerprints, Including Structural Fragment Analysis of Inhibitors versus Noninhibitors (2007)

Inhibition of cytochrome P450 (CYP) enzymes is unwanted because of the risk of severe side effects due to drug-drug interactions. We present two in silico Gaussian kernel weighted k-nearest neighbor models based on extended connectivity fingerprints that classify CYP2D6 and CYP3A4 inhibition. Data used for modeling consisted of diverse sets of 1153 and 1382 drug candidates tested for CYP2D6 and CYP3A4 inhibition in human liver microsomes. For CYP2D6, 82% of the classified test set compounds were predicted to the correct class. For CYP3A4, 88% of the classified compounds were correctly classified. CYP2D6 and CYP3A4 inhibition were additionally classified for an external test set on 14 drugs, and multidimensional scaling plots showed that the drugs in the external test set were in the periphery of the training sets. Furthermore, fragment analyses were performed and structural fragments frequent in CYP2D6 and CYP3A4 inhibitors and noninhibitors are presented.
Intracellular Generation and Accumulation of Amyloid β-Peptide Terminating at Amino Acid 42 (1997)

Amyloid beta-peptide (Abeta) is known to accumulate in senile plaques of Alzheimer's disease (AD) patients and is now widely believed to play a major role in the disease. Two populations of peptides occur terminating either at amino acid 40 or at amino acid 42 (Abeta1-40 and Abeta1-42). Alternative N-terminal cleavages produce additional heterogeneity (Abetax-40 and Abetax-42). Peptides terminating at amino acid 42 are believed to be the major player in sporadic AD as well as familial AD (FAD). Whereas the cellular mechanism for the generation of Abeta terminating at amino acid 40 is well understood, very little is known about the cleavage of Abeta after amino acid 42. By using two independent methods we demonstrate intracellular Abeta1-42 as well as Abetax-42 but less Abetax-40 and Abeta1-40 in kidney 293 cells stably transfected with wild type beta-amyloid precursor protein (betaAPP) or the FAD-associated Val/Gly mutation. Moreover, retention of betaAPP within the endoplasmic reticulum (ER) by treatment with brefeldin A does not block the cleavage at amino acid 42 but results in an increased production of all species of Abeta terminating at amino acid 42. This indicates that the cleavage after amino acid 42 can occur within the ER. Treatment of cells with monensin, which blocks transport of (betaAPP) within the Golgi causes a marked accumulation of intracellular Abetax-42 and Abetax-40. Therefore these experiments indicate that the gamma-secretase cleavage of Abeta after amino acid 42 can occur within the ER and later within the secretory pathway within the Golgi. Moreover inhibition of reinternalization by cytoplasmic deletions of betaAPP as well as inhibition of intracellular acidification by NH4Cl does not block intracellular Abeta1-42 or Abetax-42 production.
Activation of the coagulation factor VII by tissue thromboplastin and calcium (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTActivation of the coagulation factor VII by tissue thromboplastin and calciumBjarne Oesterud, Ase Berre, Anne Brit Otnaess, Firik Bjoerklid, and Hans PrydzCite this: Biochemistry 1972, 11, 15, 2853–2857Publication Date (Print):July 18, 1972Publication History Published online1 May 2002Published inissue 18 July 1972https://pubs.acs.org/doi/10.1021/bi00765a018https://doi.org/10.1021/bi00765a018research-articleACS PublicationsRequest reuse permissionsArticle Views78Altmetric-Citations32LEARN 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
Clonal Isolation of Muscle-Derived Cells Capable of Enhancing Muscle Regeneration and Bone Healing (2000)

Several recent studies suggest the isolation of stem cells in skeletal muscle, but the functional properties of these muscle-derived stem cells is still unclear. In the present study, we report the purification of muscle-derived stem cells from the mdx mouse, an animal model for Duchenne muscular dystrophy. We show that enrichment of desmin(+) cells using the preplate technique from mouse primary muscle cell culture also enriches a cell population expressing CD34 and Bcl-2. The CD34(+) cells and Bcl-2(+) cells were found to reside within the basal lamina, where satellite cells are normally found. Clonal isolation and characterization from this CD34(+)Bcl-2(+) enriched population yielded a putative muscle-derived stem cell, mc13, that is capable of differentiating into both myogenic and osteogenic lineage in vitro and in vivo. The mc13 cells are c-kit and CD45 negative and express: desmin, c-met and MNF, three markers expressed in early myogenic progenitors; Flk-1, a mouse homologue of KDR recently identified in humans as a key marker in hematopoietic cells with stem cell-like characteristics; and Sca-1, a marker for both skeletal muscle and hematopoietic stem cells. Intramuscular, and more importantly, intravenous injection of mc13 cells result in muscle regeneration and partial restoration of dystrophin in mdx mice. Transplantation of mc13 cells engineered to secrete osteogenic protein differentiate in osteogenic lineage and accelerate healing of a skull defect in SCID mice. Taken together, these results suggest the isolation of a population of muscle-derived stem cells capable of improving both muscle regeneration and bone healing.
Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations (2016)

A key functional result from somatic JAK1/2 mutations in a cancer cell is the inability to respond to interferon gamma by expressing PD-L1 and many other interferon-stimulated genes. These mutations result in a genetic mechanism for the absence of reactive PD-L1 expression, and patients harboring such tumors would be unlikely to respond to PD-1 blockade therapy. Cancer Discov; 7(2); 188-201. ©2016 AACR.See related commentary by Marabelle et al., p. 128This article is highlighted in the In This Issue feature, p. 115.