gebhart/patrepeval huggingface dataset:
Stable Conformation of an Interferon-γ Receptor Binding Peptide in Aqueous Solution Is Required for Interferon-γ Antagonist Activity (1993)

A peptide antagonist for mouse interferon-gamma (IFN-gamma) activity corresponding to the amino-terminal 39 amino acids of mouse IFN-gamma [MuIFN-gamma (1-39)] has been identified previously. In an analogous manner, we have assessed the ability of the corresponding peptide of human IFN-gamma [HuIFN-gamma (1-39)] to antagonize human IFN-gamma. HuIFN-gamma (1-39) has the ability to block the antiviral activity of human IFN-gamma in a functional assay. In receptor competition, the peptide can also block human IFN-gamma receptor binding. Surprisingly, the murine analog, MuIFN-gamma (1-39), possesses a 10-fold greater ability to block human IFN-gamma antiviral activity and receptor binding than HuIFN-gamma (1-39). Both peptides showed alpha-helical structure in water by circular dichroism, however MuIFN-gamma (1-39) possessed a greater amount of alpha-helix compared to HuIFN-gamma (1-39), suggesting a requirement for a stable secondary structure for optimal antagonist activity. In trifluoroethanol, a helix-stabilizing agent, both peptides showed relatively equal alpha-helices, suggesting that both sequences have an equal potential for helical structure. As IFN-gamma is species specific, the observation that MuIFN-gamma (1-39) can antagonize human IFN-gamma raises questions about the role of this region in species specificity. These studies provide insight into the structural requirements, both primary and secondary, for IFN-gamma receptor binding. In the future, this information, along with more detailed three-dimensional structural analyses of the peptides, could prove useful in the rational design of IFN-gamma agonists and antagonists.
Systematic review with network meta‐analysis: comparative efficacy and tolerability of different intravenous iron formulations for the treatment of iron deficiency anaemia in patients with inflammatory bowel disease (2017)

Ferric carboxymaltose was the most effective intravenous iron formulation, followed by iron sucrose. In addition, ferric carboxymaltose tended to be better tolerated. Thus, nanocolloidal IV iron products exhibit differing therapeutic and safety characteristics and are not interchangeable.
Cross-linking of cell surface ganglioside GM1 induces the selective apoptosis of mature CD+ T lymphocytes (1996)

Gangliosides are glycosphingolipids found ubiquitously on the surface of mammalian cells. They contain a ceramide tail that is inserted into the membrane and exposed carbohydrate and sialic acid moieties. The non-toxic B subunit oligomer (EtxB) of Escherichia coli heat-labile enterotoxin (Etx) is a potent immunogen in vivo and has profound modulatory effects on EtxB-primed lymphocytes in vitro, properties which are dependent on its ability to bind to GM1 ganglioside receptors. Here, it is shown that cross-linking GM1 by EtxB causes a differential effect on mature CD4(+) and CD8(+) T cells from lymph node cultures proliferating in response to an unrelated antigen, ovalbumin. Addition of EtxB to such cultures led to the complete depletion of CD8(+) T cells compared with enhanced activation of CD4(+) cells [as measured by expression of CD25 (IL-2Ralpha)]. By contrast, addition of a mutant EtxB, EtxB(G33D), which does not bind to GM1, failed to trigger CD8(+) T cell depletion. When EtxB was added to isolated non-immune CD8(+) lymphocytes rapid (12-18 h) alterations in nuclear morphology and the appearance of sub-G0/G1 levels of DNA were induced; properties which are characteristic of cells undergoing apoptosis. EtxB(G33D) failed to trigger apoptosis, indicating that the induction of the apoptotic signal was dependent on the binding of GM1. These findings provide an insight into the potent immunogenicity and immunomodulatory properties of E. coli enterotoxins as well as heralding a novel method for the selective induction of apoptosis in mature CD8(+) T lymphocytes.
Selective changes in natriuretic peptide and early response gene expression in isolated rat atria following stimulation by stretch or endothelin-1 (1994)

Endothelin-1 stimulates BNP secretion from rat atria; this is followed by an increase in BNP mRNA levels. Conversely, acute secretion of ANF by stretch or endothelin-1 is not accompanied by changes in ANF mRNA levels. Atrial stretch results in changes in the expression of the early response genes c-fos, Egr-1, and c-myc, while endothelin-1 stimulates Egr-1 expression. The specific changes in natriuretic peptide and early response gene expression reveal distinct mechanisms of modulation of atrial gene expression by mechanical and endocrine stimuli.
Von Hippel‐Lindau disease and erythrocytosis: Radioimmunoassay of erythropoietin in cyst fluid from a brainstem hemangioblastoma (1991)

A 59-year-old woman with von Hippel-Lindau disease developed erythrocytosis and a recurrent intracranial hemangioblastoma. Radioimmunoassay showed an elevated level of erythropoietin in her serum. Cyst fluid from the tumor also contained erythropoietin, concentrated a thousandfold relative to the serum level. Production of erythropoietin by hemangioblastomas may explain the erythrocytosis present in some patients with von Hippel-Lindau disease.
Structure and Function of Thrombin Receptor (1997)

Thrombin is a multifunctional serine protease generated at sites of vascular injury. While it is best known for its ability to cleave fibrinogen and trigger fibrin formation, thrombin is also a powerful agonist for a variety of cellularesponses. Thrombin acts on the vascular endothelium to stimulate production of prostacyclin, plasminogen activator inhibitor, and the potent smooth muscle cell mitogen platelet-derived growth factor. Recent studiesuggest that many of these disparate functions of thrombin are mediated by a common receptor. Robust thrombin receptor expression was noted in human atherosclerotic plaques by in situ hybridization. In the normal arterial wall, however, thrombin receptor was expressed only in endothelial cells. The high and selective expression of thrombin receptor in atherosclerotic lesionsuggests a possible role for thrombin receptor activation in restenosis and in atherogenesis itself. Thrombin receptor is activated by an unique mechanism. Its amino terminal exodomain includes a putative thrombin cleavage site resembling the known thrombin cleavage site in protein C. Carboxyl to this site was a sequence resembling the carboxyl tail of hirudin, a leech protein known to interact with thrombin's anion-binding exosite. Cleavage of extracellular amino-terminus at this site is necessary and sufficient for receptor activation. Thrombin recognizes high affinity binding site and bind with docking mechanism, and cleaves amino terminal activation peptide to unmask new amino terminus. The new amino terminus then functin as a tethered ligand and stimulates receptor, which is essentially a peptide receptor predominantly by intramolecular liganding. After activation, thrombin receptor is phosphorylated and desensitized at least in part by BARK2-like kinase. Thrombin receptor sensitivity to inhibition by BARK2 required the presence of specific serine and threonine residues in the receptor's cytoplasmic domain. After being internalized into the endosomal compartment, unlike beta2 adrenergic receptor which recycle to the plasma membrane, thrombin receptor is targeted to lysosome. This mechanism is unique in the thrombin receptor among the G-protein coupled receptors and is reasonable, because the receptor is not re-usable once activated. Thrombin inhibitors have been tried to prevent thrombin-mediated arteriosclerosis. However, difficulty in controling bleeding time was a limiting for clinical imprecation. Direct inhibitors of thrombin receptor which dissociates receptor activity from thrombin's proteolytic activity is necessary to solve this problem
Characterization of Physical and Functional Anchor Site Interactions in Human Telomerase (2007)

Telomerase is a ribonucleoprotein reverse transcriptase (RT) that processively synthesizes telomeric repeats onto the ends of linear chromosomes to maintain genomic stability. It has been proposed that the N terminus of the telomerase protein subunit, telomerase RT (TERT), contains an anchor site that forms stable interactions with DNA to prevent enzyme-DNA dissociation during translocation and to promote realignment events that accompany each round of telomere synthesis. However, it is not known whether human TERT (hTERT) can directly interact with DNA in the absence of the telomerase RNA subunit. Here we use a novel primer binding assay to establish that hTERT forms stable and specific contacts with telomeric DNA in the absence of the human telomerase RNA component (hTR). We show that hTERT-mediated primer binding can be functionally uncoupled from telomerase-mediated primer extension. Our results demonstrate that the first 350 amino acids of hTERT have a critical role in regulating the strength and specificity of protein-DNA interactions, providing additional evidence that the TERT N terminus contains an anchor site. Furthermore, we establish that the RT domain of hTERT mediates important protein-DNA interactions. Collectively, these data suggest that hTERT contains distinct anchor regions that cooperate to help regulate telomerase-mediated DNA recognition and elongation.
Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. (1979)

The specificity of human skin collagenase and of an enzyme from an invasive tumor were studied by using types I, II, III, IV, and V (AB) collagen as substrates. Human skin collagenase degraded types I, II, and III collagen, producing the characteristic 3/4 and 1/4 cleavage products, but failed to degrade type IV or V collagen. Collagenase prepared from the invasive tumors showed maximal activity after trypsin treatment. The tumor enzyme degraded type IV (basement membrane) collagen, producing fragments consistent with a single cleavage site but did not attack types I, II, III, and V collagen. Because type IV collagen prepared by pepsinization of placenta was also digested, it is likely that cleavage of type IV collagen by the tumor collagenase occurs within a largely helical domain. A type IV collagenase could play a significant role in tumor metastases and in normal tissues where basement membrane turnover takes place.
Phosphoinositide 3-Kinases γ and δ, Linkers of Coordinate C5a Receptor-Fcγ Receptor Activation and Immune Complex-induced Inflammation (2008)

Fcgamma receptors (FcgammaR) and the C5a receptor (C5aR) are key effectors of the acute inflammatory response to IgG immune complexes (IC). Their coordinated activation is critical in IC-induced diseases, although the significance of combined signaling by these two different receptor classes in tissue injury is unclear. Here we used the mouse model of the passive reverse lung Arthus reaction to define their requirements for distinct phosphoinositide 3-kinase (PI3K) activities in vivo. We show that genetic deletion of class IB PI3Kgamma abrogates C5aR signaling that is crucial for FcgammaR-mediated activation of lung macrophages. Thus, in PI3Kgamma(-/-) mice, IgG IC-induced FcgammaR regulation, cytokine release, and neutrophil recruitment were blunted. Notably, however, C5a production occurred normally in PI3Kgamma(-/-) mice but was impaired in PI3Kdelta(-/-) mice. Consequently, class IA PI3Kdelta deficiency caused resistance to acute IC lung injury. These results demonstrate that PI3Kgamma and PI3Kdelta coordinate the inflammatory effects of C5aR and FcgammaR and define PI3Kdelta as a novel and essential element of FcgammaR signaling in the generation of C5a in IC disease.
Growth Factors and Chronic Wounds: The Need to Understand the Microenvironment (1992)

The care of chronic wounds has become a major health issue in developed countries because of their increasingly elderly populations. There is hope that progress made in understanding and producing growth factors will lead to their successful use to induce faster and better healing of chronic wounds. This report will discuss growth factors in the context of their use in chronic wounds, and will focus on the importance of the wound microenvironment in determining the interactions between growth factors and wounds. We believe that a greater understanding of the chronic wound microenvironment will be of benefit in the optimal use of growth factors. In published studies, we have found that wound fluid taken from acute wounds stimulates fibroblast and endothelial cell proliferation, whereas fluid obtained from chronic non-healing wounds inhibits the growth of fibroblasts, endothelial cells, and keratinocytes. In this report, we describe the effect of these two types of wound fluid on the synthesis of extracellular matrix components. We hypothesize that the chronic wound microenvironment is generally non-conducive to cell growth, and that this may prevent a truly successful use of topical growth factors in chronic wounds. Novel approaches in the delivery of growth factors to wounds may be necessary to overcome these obstacles.
Environmentally stable chemical amplification positive resist: principle, chemistry, contamination resistance, and lithographic feasibility. (1994)

Our new environmentally stable chemical amplification positive resici named ESCAP is described, which has been designed on the basis of our annealing concept for contamination resistance. The ESCAP resist consists of a copolymer of 4-hydroxystyrene with t-hutyl acrylate and N-ca mphorsulfonyloxynaphthalimide as a nonionic organic acid generator. In contrastt to other positive chemical amplification resist systems, the ESCAP resist film can he heated above its glass transition temperature of ~I5() r'C without premature thermal degradation of the protecting group, thus allowing good annealing and reduction of the free volume. In consequence, the ESCAP resist which employs unconventionally high prehake temperature of '--l50 `'C ahsorhs N-methylpyrrolidone at a dramatically reduced rate and is extremely insensitive to the delay effect.
A new class of potent thrombin inhibitors that incorporates a scissile pseudopeptide bond (1991)

A synthetic hirudin peptide analog corresponding to N alpha-acetyl [D-Phe45, Arg psi(COCH2)47, Gly48]desulfo hirudin45-65 (P79) was synthesized. Comparative kinetic studies showed that while recombinant hirudin (HV2) is a slow-tight binding inhibitor, P79 behaves as a classical competitive inhibitor of human alpha-thrombin (Ki = 3.7 +/- 0.3 x 10(-10) M) and bovine alpha-thrombin (1.8 +/- 0.7 x 10(-9) M). P79 showed saturable inhibition of plasma APTT. The P1' subsite of P79 is isosteric with the glycine residue of the natural thrombin substrate fibrinogen, but is proteolytically stable due to the incorporation of a ketomethylene pseudopeptide bond. The model active site-directed tripeptide [D-Phe-Pro-Arg psi(COCH2)CH2COOCH3, P79L] corresponding to the amino terminal of P79 also binds competitively to the active site of alpha-thrombin and inhibited the proteolysis of a tripeptidyi substrate with a Ki = 17.9 +/- 2.1 microM (human) and 10.3 +/- 3.6 microM (bovine) alpha-thrombin. NMR experiments indicated that P79L and the corresponding amino terminal residues of P79 occupy a mutually exclusive binding site on bovine alpha-thrombin while the carboxyl terminal tail of the latter adopts a similar bound conformation as the fragment hirudin55-65 which is known to interact with the 'anion' exosite. Taken together these results provide conclusive evidence that the high antithrombin activity of N alpha-acetyl[D-Phe45, Arg psi(COCH2)47, Gly48]desulfo hirudin45-65 stems from the concurrent interaction with the catalytic site and the putative 'anion' exosite through its respective NH2- and COOH-terminal recognition sites.
The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice (2002)

Myotubularin is a ubiquitously expressed phosphatase that acts on phosphatidylinositol 3-monophosphate [PI(3)P], a lipid implicated in intracellular vesicle trafficking and autophagy. It is encoded by the MTM1 gene, which is mutated in X-linked myotubular myopathy (XLMTM), a muscular disorder characterized by generalized hypotonia and muscle weakness at birth leading to early death of most affected males. The disease was proposed to result from an arrest in myogenesis, as the skeletal muscle from patients contains hypotrophic fibers with centrally located nuclei that resemble fetal myotubes. To understand the physiopathological mechanism of XLMTM, we have generated mice lacking myotubularin by homologous recombination. These mice are viable, but their lifespan is severely reduced. They develop a generalized and progressive myopathy starting at around 4 weeks of age, with amyotrophy and accumulation of central nuclei in skeletal muscle fibers leading to death at 6-14 weeks. Contrary to expectations, we show that muscle differentiation in knockout mice occurs normally. We provide evidence that fibers with centralized myonuclei originate mainly from a structural maintenance defect affecting myotubularin-deficient muscle rather than a regenerative process. In addition, we demonstrate, through a conditional gene-targeting approach, that skeletal muscle is the primary target of murine XLMTM pathology. These mutant mice represent animal models for the human disease and will be a valuable tool for understanding the physiological role of myotubularin.
Comparison of Correspondence Analysis Methods for Synonymous Codon Usage in Bacteria (2008)

Synonymous codon usage varies both between organisms and among genes within a genome, and arises due to differences in G + C content, replication strand skew, or gene expression levels. Correspondence analysis (CA) is widely used to identify major sources of variation in synonymous codon usage among genes and provides a way to identify horizontally transferred or highly expressed genes. Four methods of CA have been developed based on three kinds of input data: absolute codon frequency, relative codon frequency, and relative synonymous codon usage (RSCU) as well as within-group CA (WCA). Although different CA methods have been used in the past, no comprehensive comparative study has been performed to evaluate their effectiveness. Here, the four CA methods were evaluated by applying them to 241 bacterial genome sequences. The results indicate that WCA is more effective than the other three methods in generating axes that reflect variations in synonymous codon usage. Furthermore, WCA reveals sources that were previously unnoticed in some genomes; e.g. synonymous codon usage related to replication strand skew was detected in Rickettsia prowazekii. Though CA based on RSCU is widely used, our evaluation indicates that this method does not perform as well as WCA.
Nucleotide sequence and genetic analysis of the neuD and neuB genes in region 2 of the polysialic acid gene cluster of Escherichia coli K1 (1995)

The K1 capsular polysaccharide, a polymer of sialic acid, is an important virulence determinant of extraintestinal pathogenic Escherichia coli. The genes responsible for the synthesis and expression of the polysialic acid capsule of E. coli K1 are located on the 17-kb kps gene cluster, which is functionally divided into three regions. Central region 2 encodes proteins necessary for the synthesis, activation, and polymerization of sialic acid, while flanking regions 1 and 3 are involved in polymer transport to the cell surface. In this study, we identified two genes at the proximal end of region 2, neuD and neuB, which encode proteins with predicted sizes of 22.7 and 38.7 kDa, respectively. Several observations suggest that the neuB gene encodes sialic acid synthase. EV24, a neuB chromosomal mutant that expresses a capsule when provided exogenous sialic acid, could be complemented in trans by the cloned neuB gene. In addition, NeuB has significant sequence similarity to the product of the cpsB gene of Neisseria meningitidis group B, which is postulated to encode sialic acid synthase. We also present data indicating that neuD has an essential role in K1 polymer production. Cells harboring pSR426, which contains all of region 2 but lacks region 1 and 3 genes, produce an intracellular polymer. In contrast, no polymer accumulated in cells carrying a derivative of pSR426 lacking a functional neuD gene. Unlike strains with mutations in neuB, however, neuD mutants are not complemented by exogenous sialic acid, suggesting that NeuD is not involved in sialic acid synthesis. Additionally, cells harboring a mutation in neuD accumulated sialic acid and CMP-sialic acid. We also found no significant differences between the endogenous and exogenous sialyltransferase activities of a neuD mutant and the wild-type organism. NeuD shows significant similarity to a family of bacterial acetyltransferases, leading to the theory that NeuD is an acetyltransferase which may exert its influences through modification of other region 2 proteins.
Relationship of normal CDF1 mouse leukocyte kinetics to growth characteristics of leukemia L1210. (1969)

Leukocyte kinetics were studied in the CDF1 mouse using liquid scintillation and radioautographic technics. Although the latter method provides more detailed information, the former technic is readily adaptable to experimental manipulations. The kinetics of mouse leukocytes are different from those in man. Either marrow storage and transit times are different or the generation times of mouse marrow progenitor cells is shorter. Data presented in this study and those available in the literature support the latter concept. The selective therapeutic advantage of the mouse marrow cells is probably related to the presence of nonproliferating cells inaccessible to chemotherapy as reported in the literature. Knowledge of both normal and tumor cell kinetics is essential if drug scheduling is to be placed on a more rational basis.
Optical investigation of highly strained InGaAs-GaAs multiple quantum wells (1987)

Low-temperature optical transmission spectra of several InxGa1−xAs/GaAs strained multiple quantum wells (MQWs) with different well widths and In mole fractions have been measured. The excitonic transitions up to 3C-3H are observed. The notation nc-mH(L) is used to indicate the transitions related to the nth conduction and mth valence heavy (light) hole subbands. Steplike structures corresponding to band-to-band transitions are also observed, which are identified as 1C-1L transitions. The calculated transition energies, taking into account both the strain and the quantum well effects, are in good agreement with the measured values. In these calculations the lattice mismatch between the GaAs buffer and the InGaAs/GaAs MQW is taken into account and the valence-band offset Qv is chosen as an adjustable parameter. By fitting the experimental results to our calculations, we conclude that the light holes are in GaAs barrier region (type II MQW) and the valence-band offset Qv is determined to be 0.30. A possible system in which the transition from type I to type II for light holes might be observed is also discussed.