gebhart/patrepeval huggingface dataset:
SalmonellaFlagellin Induces Tumor Necrosis Factor Alpha in a Human Promonocytic Cell Line (1998)

During infection of the gastrointestinal tract, salmonellae induce cytokine production and inflammatory responses which are believed to mediate tissue damage in the host. In a previous study, we reported that salmonellae possess the ability to stimulate tumor necrosis factor alpha (TNF-alpha) accumulation in primary human monocytes, as well as in the human promonocytic cell line U38. In this model system, cytokine upregulation is not due to lipopolysaccharide but is mediated by a released protein. In the present study, TnphoA transposon mutagenesis was used to identify the TNF-alpha-inducing factor. A mutant Salmonella strain which lacks the ability to induce TNF-alpha was isolated from a TnphoA library. Genetic analysis of this mutant demonstrated that the hns gene has been interrupted by transposon insertion. The hns gene product is a DNA-binding protein that regulates the expression of a variety of unrelated genes in salmonellae. One of the known targets of histone-like protein H1 is flhDC, the master operon which is absolutely required for flagellar expression. Analysis of other nonflagellated mutant Salmonella strains revealed a correlation between the ability to induce TNF-alpha and the expression of the phase 1 filament subunit protein FliC. Complementation experiments demonstrated that FliC is sufficient to restore the ability of nonflagellated mutant Salmonella strains to upregulate TNF-alpha, whereas the phase 2 protein FljB appears to complement to a lesser extent. In addition, Salmonella FliC can confer the TNF-alpha-inducing phenotype on Escherichia coli, which otherwise lacks the activity. Furthermore, assembly of FliC into complete flagellar structures may not be required for induction of TNF-alpha.
Health Behaviour Change Interventions for the Promotion of Physical Activity in Rheumatoid Arthritis: A Systematic Review (2013)

Due to methodological flaws and a lack of comparison with usual care, it is not possible to conclude whether HBC interventions can increase PA in the RA population. Although it is possible to highlight promising elements of HBC interventions, such as goal setting and feedback on performance, further research on all specific components, including information provision, behaviour contracts and problem solving, is required to establish conclusive clinical guidelines.
A Novel Role for Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 as a Determinant of Gemcitabine Chemoresistance in Pancreatic Adenocarcinoma Cells (2004)

Most patients with pancreatic adenocarcinoma present with surgically incurable disease. Gemcitabine, the principal agent used to treat such patients, has little impact on outcome. Overexpression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6, a feature of this malignancy, is associated with resistance to anoikis and increased metastasis. The purpose of this study was to determine the role of CEACAM6 in cellular chemoresistance to gemcitabine. CEACAM6 was stably overexpressed in Capan2 cells, which inherently express very low levels of the protein. Suppression of CEACAM6 expression was achieved in BxPC3 cells, which inherently overexpress CEACAM6, by stable transfection of a CEACAM6 small interfering RNA-generating vector. The effects of modulating CEACAM6 expression on gemcitabine-induced cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay, flow cytometric apoptosis quantification, caspase profiling, and Western analysis of cytoplasmic cytochrome c release. The roles of Akt and c-Src kinases as downstream targets of CEACAM6 signaling were examined. Stable overexpression of CEACAM6 in Capan2 increased gemcitabine chemoresistance, whereas CEACAM6 gene silencing in BxPC3 markedly increased the sensitivity of these cells to gemcitabine. Differential expression of CEACAM6 modulates Akt activity in a c-Src-dependent manner, and CEACAM6 overexpression appears to protect cells from cytochrome c-induced caspase 3 activation and apoptosis.
Zinc concentration in patients with iron overload receiving oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one or desferrioxamine. (1994)

In contrast to DFX, L1 treatment is associated with increased zinc loss. This, however, is modest and does not lead in most patients to subnormal serum zinc concentrations. In a few patients whose negative zinc balance may give rise to symptoms, zinc supplementation rapidly corrects the deficit.
Multiple Sclerosis and High Incidence of a B Lymphocyte Antigen (1976)

Multiple sclerosis patients were tested for six new antigens present on human B lymphocytes. The group 4 specificity occurred in 83.9% of the 56 patients as compared to 32.5 percent in 72 healthy controls (P less than .003). The antiserums defining the five other B lymphocyte specificities reacted at a lower frequency to B cells from multiple sclerosis patients, showing that increased reactivity to group 4 antiserum was specific. Linkage of a hypothesized multiple sclerosis susceptibility gene with certain haplotypes of HLA-A3, HLA-B7 HLA-DW2, and the new B group 4 can be inferred.
Identification and characterization of two α-1,6-mannosyltransferases, Anl1p and Och1p, in the yeast Yarrowia lipolytica (2004)

In this study, the identification and characterization of the Yarrowia lipolytica homologues of Saccharomyces cerevisiae α -1,6-mannosyltransferases Anp1p and Och1p, designated YlAnl1p and YlOch1p, are described. In order to confirm the function of the Y. lipolytica proteins, including the previously isolated YlMnn9p, in the N -glycosylation pathway, a phenotypic analysis of the disrupted strains Δ Ylmnn9 , Δ Ylanl1 , Δ Yloch1 , Δ Ylanl1 Δ Ylmnn9 and Δ Ylmnn9 Δ Yloch1 was performed. Disruption of the YlMNN9 , YlANL1 and YlOCH1 genes caused an increased sensitivity to SDS, compatible with a glycosylation defect, and to Calcofluor White, characteristic of cell-wall defects. Moreover, Western-blot analysis of a heterologous glycosylated protein confirmed a direct role of YlMnn9p and YlAnl1p in the N -glycosylation process. These mutant strains, Δ Ylmnn9 , Δ Ylanl1 , Δ Yloch1 , Δ Ylanl1 Δ Ylmnn9 and Δ Ylmnn9 Δ Yloch1 may thus be used to establish a model for the Y. lipolytica N -linked glycosylation pathway.
Cell death: programmed, apoptosis, necrosis, or other? (1995)

There are at least two major types of active or physiological cell death. The most well-known form, apoptosis or Type I, involves early nuclear collapse, condensation of chromatin, generation of nucleosomal ladders, and cell fragmentation with little or no early alteration of lysosomes. It is most commonly seen in cells deriving from highly mitotic lines, and the cells are phagocytosed by neighboring cells or infiltrating macrophages. In metamorphosing or secretory cells, and under conditions where the majority of cells die, the bulk of the cytoplasm is consumed by expansion of the lysosomal system well before nuclear collapse is manifest. This form of cell death has been termed Type II cell death, and we revert to this terminology. The requirement for protein synthesis is more characteristic of Type II cell death in developmental situations than it is for Type I cell death. The variations seen force a reassessment of those aspects of physiological cell death that are truly universal, thereby focusing attention on the biology of the process. A better understanding of the biology and morphology of dying cells will help clarify the significance of the molecular and biochemical findings.
Microcontact Printing for Precise Control of Nerve Cell Growth in Culture (1999)

Microcontact printing, facilitated by silane linker chemistry and high-relief stamps, creates precise patterns of proteins, which in turn control growth of hippocampal neurons in culture. This additive, multi-mask technique permits several different molecules to be patterned on the same substrate. The covalent linker technology permits relatively long-term (two-week) compliance of neurons to the stamped pattern against a polyethylene glycol background. When polylysine was stamped adjacent to a laminin/polylysine mixture, neural somata and dendrites preferred the polylysine while axons prefer the mixture or the border between the two.
Uridine Addition After MicroRNA-Directed Cleavage (2004)

One of the important roles of microRNA (miRNA) is to direct the cleavage of messenger RNA (mRNA). However, the mechanisms of decay of the cleaved mRNA products is not well understood. We show that miRNA-directed cleavage products in organisms as diverse as Arabidopsis, mouse, and Epstein-Barr virus have at their 3' ends a stretch (1 to 24 nucleotides) of oligouridine posttranscriptionally added downstream of the cleavage site. This 3' uridine addition, as shown for Arabidopsis, is correlated with decapping and 5' shortening of the cleaved products, suggesting a mechanistic step in the miRNA-directed mRNA decay mechanism.
Reduced hepatic expression of farnesoid X receptor in hereditary cholestasis associated to mutation in ATP8B1 (2004)

Farnesoid X receptor (FXR) is a transcription factor that controls bile acid homeostasis. The phenotype of Fxr null mice is characterized by hypercholanaemia, impaired secretion of bile acids and failure to thrive. Human disorders with these characteristics include FIC1 disease (caused by mutations in ATP8B1, which encodes a putative aminophospholipid translocase, FIC1, whose function in bile handling is unknown) and bile salt export pump (BSEP) disease (caused by mutation in ABCB11, which encodes BSEP, the primary canalicular bile salt export pump). We investigated the possibility of hepatic down-regulation of FXR in FIC1 disease and BSEP disease. Three siblings with this phenotype, born to consanguine parents, were initially studied. The children were demonstrated to be compound heterozygotes for missense and nonsense mutations in ATP8B1. Expression of specific genes in liver was analysed, comparing one of these siblings with a child homozygous for missense mutation in ABCB11, as well as with a child having idiopathic cholestatic liver disease, a child with extrahepatic biliary atresia and a normal organ donor. The expression of two main FXR isoforms was specifically decreased in the liver of the FIC1 disease patient. A consistent and concomitant reduction in messenger RNA levels of FXR targets, such as BSEP and small heterodimer partner, was also found. Gene-profiling experiments identified 163 transcripts whose expression changed significantly in FIC1-disease liver. Of note was that several genes involved in synthesis, conjugation and transport of bile acids were down-regulated. A cluster of genes involved in lipid metabolism was also differentially expressed. Our findings suggest that hepatic down-regulation of FXR contributes to the severe cholestasis of FIC1 disease.
Improving the Mismatch between Light and Nanoscale Objects with Gold Bowtie Nanoantennas (2005)

Metallic bowtie nanoantennas should provide optical fields that are confined to spatial scales far below the diffraction limit. To improve the mismatch between optical wavelengths and nanoscale objects, we have lithographically fabricated Au bowties with lengths approximately 75 nm and gaps of tens of nm. Using two-photon-excited photoluminescence of Au, the local intensity enhancement factor relative to that for the incident diffraction-limited beam has been experimentally determined for the first time. Enhancements >10(3) occur for 20 nm gap bowties, in good agreement with theoretical simulations.
A British experience of surgical voice restoration techniques as a secondary procedure following total laryngectomy (1987)

An earlier paper (Cheesman et al., 1985) described assessment procedures for 'failed' oesophageal speakers who were referred to Charing Cross Hospital for possible Surgical Voice Restoration in 1983-4. This paper presents the results of surgical voice restoration in the first fifty laryngectomized patients referred and analyses the reasons for failure in those where surgical voice restoration was unsuccessful. 94 per cent of patients who underwent secondary voice restoration were successful at two weeks post-surgery, but this success rate dropped to 73 per cent at three months. Reasons for this are explained and the pre-requisites for a successful surgical voice restoration are indicated.
PSAMMOMYS OBESUS OF THE JERUSALEM COLONY: A MODEL FOR NUTRITIONALLY INDUCED, NON-INSULIN-DEPENDENT DIABETES (1993)

Article PSAMMOMYS OBESUS OF THE JERUSALEM COLONY: A MODEL FOR NUTRITIONALLY INDUCED, NON-INSULIN-DEPENDENT DIABETES was published on April 1, 1993 in the journal Journal of Basic and Clinical Physiology and Pharmacology (volume 4, issue 1-2).
Increased Bax Expression Is Associated with Cell Death Induced by Ganciclovir in a Herpes Thymidine Kinase Gene-Expressing Glioma Cell Line (1999)

The herpes simplex virus thymidine kinase gene (HSV-tk) was stably transfected into rat C6 glioma cells (C6tk) in order to characterize the mechanisms underlying cell toxicity induced in vitro by the guanosine analog ganciclovir (GCV). The results demonstrate the efficiency of the HSV-tk/GCV system in ablating most of the tumoral cells within 7 to 8 days of treatment with 20 mivroM GCV; however, a few cells still survive. C6tk cells arrest in the S phase of the cell cycle after 2 days of drug treatment before undergoing cell death. Microscopic analysis reveals dying cells with ultrastructural characteristics consistent with apoptosis; we cannot rule out, however, that necrotic cell death may also be occurring. The cytotoxicity induced by GCV is not associated with changes in the expression of p53 protein, suggesting that cell cycle arrest and cell death may occur through a p53-independent pathway. C6tk cells constitutively express Bcl-xL and Bax proteins; when exposed to GCV, Bcl-xL levels do not change but Bax accumulation is rapidly induced. These findings suggest that the balance between Bcl-xL and Bax proteins may be of importance in determining the sensitivity of tumoral cells to GCV.
A myostatin inhibitor (propeptide-Fc) increases muscle mass and muscle fiber size in aged mice but does not increase bone density or bone strength (2013)

Loss of muscle and bone mass with age are significant contributors to falls and fractures among the elderly. Myostatin deficiency is associated with increased muscle mass in mice, dogs, cows, sheep and humans, and mice lacking myostatin have been observed to show increased bone density in the limb, spine, and jaw. Transgenic overexpression of myostatin propeptide, which binds to and inhibits the active myostatin ligand, also increases muscle mass and bone density in mice. We therefore sought to test the hypothesis that in vivo inhibition of myostatin using an injectable myostatin propeptide (GDF8 propeptide-Fc) would increase both muscle mass and bone density in aged (24 mo) mice. Male mice were injected weekly (20 mg/kg body weight) with recombinant myostatin propeptide-Fc (PRO) or vehicle (VEH; saline) for four weeks. There was no difference in body weight between the two groups at the end of the treatment period, but PRO treatment significantly increased mass of the tibialis anterior muscle (+ 7%) and increased muscle fiber diameter of the extensor digitorum longus (+ 16%) and soleus (+ 6%) muscles compared to VEH treatment. Bone volume relative to total volume (BV/TV) of the femur calculated by microCT did not differ significantly between PRO- and VEH-treated mice, and ultimate force (Fu), stiffness (S), toughness (U) measured from three-point bending tests also did not differ significantly between groups. Histomorphometric assays also revealed no differences in bone formation or resorption in response to PRO treatment. These data suggest that while developmental perturbation of myostatin signaling through either gene knockout or transgenic inhibition may alter both muscle and bone mass in mice, pharmacological inhibition of myostatin in aged mice has a more pronounced effect on skeletal muscle than on bone.
Tobacco mosiac virus particle structure and the initiation of disassembly (1999)

The structure of an intact tobacco mosaic virus (TMV) particle was determined at 2.9 A resolution using fibre diffraction methods. All residues of the coat protein and the three nucleotides of RNA that are bound to each protein subunit were visible in the electron density map. Examination of the structures of TMV, cucumber green mottle mosaic virus and ribgrass mosaic virus, and site-directed mutagenesis experiments in which carboxylate groups were changed to the corresponding amides, showed that initial stages of disassembly are driven by complex electrostatic interactions involving at least seven carboxylate side-chains and a phosphate group. The locations of these interactions can drift during evolution, allowing the viruses to evade plant defensive responses that depend on recognition of the viral coat protein surface.
Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models (2016)

Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645-1648) in the design of B-domain-deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by furin is in fact deleterious to FVIII-BDD secretion and procoagulant activity. Inhibition of furin increases the secretion and decreases the intracellular retention of FVIII-BDD protein in mammalian cells. Our new variant (FVIII-ΔF), in which this recognition motif is removed, efficiently circumvents furin. FVIII-ΔF demonstrates increased recombinant protein yields, enhanced clotting activity, and higher circulating FVIII levels after adeno-associated viral vector-based liver gene therapy in a murine model of severe hemophilia A (HA) compared with FVIII-BDD. Moreover, we observed an amelioration of the bleeding phenotype in severe HA dogs with sustained therapeutic FVIII levels after FVIII-ΔF gene therapy at a lower vector dose than previously employed in this model. The immunogenicity of FVIII-ΔF did not differ from that of FVIII-BDD as a protein or a gene therapeutic. Thus, contrary to previous suppositions, FVIII variants that can avoid furin processing are likely to have enhanced translational potential for HA therapy.
B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin (2010)

Recombinant BLyS/APRIL heterotrimers have biologic activity and are inhibited by atacicept and BCMA-Ig, but not by BAFF-R-Ig. A novel immunoassay demonstrated that native BLyS/APRIL heterotrimers, as well as BLyS and APRIL homotrimers, are elevated in patients with autoimmune diseases.
Wound-Induced Proteinase Inhibitor in Plant Leaves: A Possible Defense Mechanism against Insects (1972)

Wounding of the leaves of potato or tomato plants by adult Colorado potato beetles, or their larvae, induces a rapid accumulation of a proteinase inhibitor throughout the plants' tissues that are exposed to air. This effect of insect damage can be simulated by mechanically wounding the leaves. The transport of a factor out of damaged leaves takes place rapidly after the wound is inflicted and the levels of proteinase inhibitor, in both damaged and adjacent leaves, rises strikingly within a few hours. The rapid accumulation of a powerful inhibitor of major intestinal proteinases of animals in response to wounding of the leaves is probably a defense mechanism.
Ductal Carcinoma in Situ: One Size does Not Fit All (2010)

Evaluation of: Kerlikowske K, Molinaro AM, Gauthier ML et al.: Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J. Natl Cancer Inst. 102(9), 627–637 (2010). In a population-based case–control study cohort of 1162 women who were diagnosed with ductal carcinoma in situ (DCIS) and treated by lumpectomy alone from 1983 to 1994, a comprehensive analysis of biomarkers including estrogen receptor, progesterone receptor, p53, Her2/neu, p16, Ki67 and COX-2 in a selected cohort of 329 women was performed. Overall, patients presenting with palpable DCIS and patients who were triple positive for p16, COX-2 and Ki67 were found on multivariate analysis to have a significantly increased risk of subsequent invasive carcinoma. Neither nuclear grade nor histopathologic characteristics were associated with subsequent invasive carcinoma. Recurrent DCIS was associated with disease extent of 10 mm or more, positive resection margins, high nuclear grade, extensive necrosis and also associated with the biomarker combinations.
Comprehensive Chromatographic and Spectroscopic Methods for the Separation and Identification of Intact Glucosinolates (1996)

Much effort has been devoted to developing methods for the efficient isolation and identification of glucosinolates. Existing methods for separation involve ion exchange, GLC, and HPLC (mostly after chemical modification by enzymatic sulfate removal and/or silylation). We demonstrate a simple and direct strategy for analyzing the glucosinolate content of plant extracts, made possible by a new combination of widely available techniques: (a) reverse-phase paired-ion chromatography (PIC) of plant extracts, (b) hydrolysis of glucosinolates by myrosinase and quantitation of resulting isothiocyanates by cyclocondensation with 1, 2-benzenedithiol; (c) a novel method for replacing the PIC counterions by ammonium ions, permitting direct bioassay, mass, and 1H NMR spectrometry; (d) mass spectrometric analysis of ammonium salts by negative-ion fast atom bombardment (FAB) to determine m/z of the [M - H]- ion, and by chemical ionization (CI) in ammonia to obtain accurate masses of characteristic fragment ions, principally [R-CN:NH4]+, [R-CH=NOH:H]+ and [R-CH=NOH:NH4]+; and (e) high-resolution 1H NMR spectroscopy of intact glucosinolates. FAB and CI mass spectra, as well as high-resolution 1H NMR spectra were obtained for a variety of glucosinolate standards. The results provide guidance for the isolation and characterization of unknown glucosinolates from plants. These combined procedures were applied to a sample of broccoli (cultivar SAGA), in order to resolve and identify its major glucosinolates: 4-methylsulfinylbutyl glucosinolate (glucoraphanin) and 4-methylthiobutyl glucosinolate (glucoerucin). Thus, this analytical strategy provides a powerful technique for identifying and quantitating glucosinolates in plant extracts without resorting to derivatization.