gebhart/patrepeval huggingface dataset:
Biological activities of toxins A and B of Clostridium difficile (1982)

Examination of the biological activities of the two known toxins of Clostridium difficile revealed that one of the toxins (toxin A) elicited a hemorrhagic fluid response in rabbit intestinal loops and a positive fluid response in infant mice. The other toxin (toxin B) did not produce a significant fluid response in either model, although the toxin was more lethal in infant mice. Both toxins elicited erythematous and hemorrhagic skin reactions and increased vascular permeability in rabbit skin.
Lung Damage in Mice Following Intraperitoneal Injection of Butylated Hydroxytoluene (1972)

SummaryButylated hydroxytoluene was administered intraperitoneally to two strains of mice in the dose range 0.004-2.5 g/kg. Histological examination of the lung tissue revealed thickened interalveolar septa, congestion and a general pattern of tissue disorganization at doses of 0.25 g/kg and above. The observed effects are apparently reversible and have a threshold in the vicinity of 0.04 g/kg.
The Generation of Mature, Single-Positive Thymocytes In Vivo Is Dysregulated by CD69 Blockade or Overexpression (2002)

During development in the thymus, mature CD4+ or CD8+ cells are derived from immature CD4+CD8+ cells through a series of selection events. One of the hallmarks of this maturation process is the expression of CD69, which first appears on thymocytes as they begin positive selection. We have used blockade and overexpression of CD69 to determine the role of CD69 in thymocyte development. Blockade of CD69 led to a reduction in single-positive cells and a concomitant increase in double-positive cells in the thymus. Overexpression of a CD69 transgene in the thymus resulted in a dramatic increase in both CD8SP and CD4SP cells. Coexpression with a TCR transgene demonstrated that both positive and negative selection were enhanced by the increased levels of CD69 on thymocytes. Finally, mice overexpressing CD69 displayed a sharp reduction in the number of T cells in the spleen and lymph node. Taken as a whole, these data suggest the involvement of CD69 in the process of selection and maturation during the trafficking of thymocytes to the medulla.
On‐line separations combined with MS for analysis of glycosaminoglycans (2008)

The glycosaminoglycan (GAG) family of polysaccharides includes the unsulfated hyaluronan and the sulfated heparin, heparan sulfate, keratan sulfate, and chondroitin/dermatan sulfate. GAGs are biosynthesized by a series of enzymes, the activities of which are controlled by complex factors. Animal cells alter their responses to different growth conditions by changing the structures of GAGs expressed on their cell surfaces and in extracellular matrices. Because this variation is a means whereby the functions of the limited number of protein gene products in animal genomes is elaborated, the phenotypic and functional assessment of GAG structures expressed spatially and temporally is an important goal in glycomics. On-line mass spectrometric separations are essential for successful determination of expression patterns for the GAG compound classes due to their inherent complexity and heterogeneity. Options include size exclusion, anion exchange, reversed phase, reversed phase ion pairing, hydrophilic interaction, and graphitized carbon chromatographic modes and capillary electrophoresis. This review summarizes the application of these approaches to on-line MS analysis of the GAG classes.
Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma (2006)

RASSF2 can bind directly to K-Ras and function as a negative effector of Ras protein. RASSF2A is the only isoform of RASSF2 that contains CpG islands in its promoter and it has been reported to be inactivated by its promoter methylation in several human cancers. In the present study, we investigated the correlation of RASSF2A expression with its promoter methylation in nasopharyngeal carcinoma (NPC). Expression of RASSF2A was down-regulated in 80% (4/5) of NPC cell lines. Decreased RASSF2A expression was also observed in NPC primary tumors compared with normal nasopharyngeal epithelia. Promoter methylation of RASSF2A could be detected in all the RASSF2A-silenced cell lines (4/5) of the NPC cell lines and 50.9% (27/53) of primary tumors, but not in any of the normal epithelia. RASSF2A-methylated cases showed a significantly lower level of RASSF2A expression than unmethylated cases. Loss of RASSF2A expression can be greatly restored by the methyltransferase inhibitor 5-aza-dC in NPC cell lines. In addition, patients with methylated RASSF2A presented a higher frequency of lymph node metastasis (p < 0.05). Ectopic expression of RASSF2A in RASSF2A-silenced and -methylated NPC cell line CNE2 shows that RASSF2A could inhibit cell cycle progression, colony formation and cell migration, which provided further evidence that RASSF2A is a candidate tumor suppressor gene. In conclusion, RASSF2A, a candidate tumor suppressor gene (TSG), is frequently inactivated by its promoter methylation and this aberrant methylation correlates with lymph node metastasis in NPC.
Development of Normal Mice from Oocytes Injected with Secondary Spermatocyte Nuclei1 (1995)

This study shows that the nucleus of the secondary spermatocyte can participate in syngamy and normal embryonic development. Spermatogenic cells were released from the seminiferous tubules of adult mice, and the secondary spermatocytes were selected according to the size of the whole cell and nucleus. The accuracy of this selection, evaluated by chromosome analysis, was 86%. Nuclei of presumptive secondary spermatocytes were freed from the cytoplasm and then injected individually into mature oocytes. This process itself did not activate the oocytes. The oocytes were electroactivated about 2 h after injection, at which time prematurely condensed chromosomes of the spermatocyte had become associated with the microtubules of a spindle. Following activation, the chromosomes of both the oocyte and spermatocyte completed their second meiotic division, culminating in the extrusion of two separate polar bodies and the formation of one male and one female pronucleus in about 75% of the oocytes into which spermatocyte nuclei had been injected. Two- or four-cell embryos arising from such oocytes were randomly selected and transplanted to foster mothers. Twenty-four percent developed into normal fertile offspring. The young born later to these offspring were all normal. The results of this study indicate that gametic imprinting of mouse spermatogenic cells is completed either in the testis before the second meiotic division or within the cytoplasm of a mature oocyte after artificial nuclear transfer.
Bone Marrow X Kinase–Mediated Signal Transduction in Irradiated Vascular Endothelium (2008)

Radiation-induced activation of the phosphatidyl inositol-3 kinase/Akt signal transduction pathway requires Akt binding to phosphatidyl-inositol phosphates (PIP) on the cell membrane. The tyrosine kinase bone marrow X kinase (Bmx) binds to membrane-associated PIPs in a manner similar to Akt. Because Bmx is involved in cell growth and survival pathways, it could contribute to the radiation response within the vascular endothelium. We therefore studied Bmx signaling within the vascular endothelium. Bmx was activated rapidly in response to clinically relevant doses of ionizing radiation. Bmx inhibition enhanced the efficacy of radiotherapy in endothelial cells as well as tumor vascular endothelium in lung cancer tumors in mice. Retroviral shRNA knockdown of Bmx protein enhanced human umbilical vascular endothelial cell (HUVEC) radiosensitization. Furthermore, pretreatment of HUVEC with a pharmacologic inhibitor of Bmx, LFM-A13, produced significant radiosensitization of endothelial cells as measured by clonogenic survival analysis and apoptosis as well as functional assays including cell migration and tubule formation. In vivo, LFM-A13, when combined with radiation, resulted in significant tumor microvascular destruction as well as enhanced tumor growth delay. Bmx therefore represents a molecular target for the development of novel radiosensitizing agents.
Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties (2010)

Previous reports suggested that culture as 3D aggregates or as spheroids can increase the therapeutic potential of the adult stem/progenitor cells referred to as mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). Here we used a hanging drop protocol to prepare human MSCs (hMSCs) as spheroids that maximally expressed TNFalpha stimulated gene/protein 6 (TSG-6), the antiinflammatory protein that was expressed at high levels by hMSCs trapped in the lung after i.v. infusion and that largely explained the beneficial effects of hMSCs in mice with myocardial infarcts. The properties of spheroid hMSCs were found to depend critically on the culture conditions. Under optimal conditions for expression of TSG-6, the hMSCs also expressed high levels of stanniocalcin-1, a protein with both antiinflammatory and antiapoptotic properties. In addition, they expressed high levels of three anticancer proteins: IL-24, TNFalpha-related apoptosis inducing ligand, and CD82. The spheroid hMSCs were more effective than hMSCs from adherent monolayer cultures in suppressing inflammatory responses in a coculture system with LPS-activated macrophages and in a mouse model for peritonitis. In addition, the spheroid hMSCs were about one-fourth the volume of hMSCs from adherent cultures. Apparently as a result, larger numbers of the cells trafficked through the lung after i.v. infusion and were recovered in spleen, liver, kidney, and heart. The data suggest that spheroid hMSCs may be more effective than hMSCs from adherent cultures in therapies for diseases characterized by sterile tissue injury and unresolved inflammation and for some cancers that are sensitive to antiinflammatory agents.
Structures of eleven zervamicin and two emerimicin peptide antibiotics studied by fast atom bombardment mass spectrometry (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructures of eleven zervamicin and two emerimicin peptide antibiotics studied by fast atom bombardment mass spectrometryKenneth L. Rinehart Jr., Larry A. Gaudioso, Michael L. Moore, Ramesh C. Pandey, J. Carter Cook Jr., Michael Barber, R. Donald Sedgwick, Robert S. Bordoli, Andrew N. Tyler, and Brian N. GreenCite this: J. Am. Chem. Soc. 1981, 103, 21, 6517–6520Publication Date (Print):October 1, 1981Publication History Published online1 May 2002Published inissue 1 October 1981https://pubs.acs.org/doi/10.1021/ja00411a052https://doi.org/10.1021/ja00411a052research-articleACS PublicationsRequest reuse permissionsArticle Views203Altmetric-Citations104LEARN 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
The R1 gene for potato resistance to late blight (Phytophthora infestans) belongs to the leucine zipper/NBS/LRR class of plant resistance genes (2002)

Late blight caused by the oomycete Phytophthora infestans is the most destructive disease in potato cultivation worldwide. New, more virulent P. infestans strains have evolved which overcome the genetic resistance that has been introgressed by conventional breeding from wild potato species into commercial varieties. R genes (for single-gene resistance) and genes for quantitative resistance to late blight are present in the germplasm of wild and cultivated potato. The molecular basis of single-gene and quantitative resistance to late blight is unknown. We have cloned R1, the first gene for resistance to late blight, by combining positional cloning with a candidate gene approach. The R1 gene is member of a gene family. It encodes a protein of 1293 amino acids with a molecular mass of 149.4 kDa. The R1 gene belongs to the class of plant genes for pathogen resistance that have a leucine zipper motif, a putative nucleotide binding domain and a leucine-rich repeat domain. The most closely related plant resistance gene (36% identity) is the Prf gene for resistance to Pseudomonas syringae of tomato. R1 is located within a hot spot for pathogen resistance on potato chromosome V. In comparison to the susceptibility allele, the resistance allele at the R1 locus represents a large insertion of a functional R gene.
Combining random forest with multi-block local binary pattern feature selection for multiclass head pose estimation (2017)

A new head pose estimation technique based on Random Forest (RF) and texture features for facial image analysis using a monocular camera is proposed in this paper, especially about how to efficiently combine the random forest and the features. In the proposed technique a randomized tree with useful attributes is trained to improve estimation accuracy and tolerance of occlusions and illumination. Specifically, a number of features including Multi-scale Block Local Block Pattern (MB-LBP) are extracted from an image, and random features such as the MB-LBP scale parameters, a block coordinate, and a layer of an image pyramid in the feature pool are used for training the tree. The randomized tree aims to maximize the information gain at each node while random samples traverse the nodes in the tree. To this aim, a split function considering the uniform property of the LBP feature is developed to move sample blocks to the left or the right children nodes. The trees are independently trained with random inputs, yet they are grouped to form a random forest so that the results collected from the trees are used for make the final decision. Precisely, we use a Maximum-A-Posteriori criterion in the decision. It is demonstrated with experimental results that the proposed technique provides significantly enhanced classification performance in the head pose estimation in various conditions of illumination, poses, expressions, and facial occlusions.
Specificity of flavobacterial glycuronidases acting on disaccharides derived from glycosaminoglycans (1977)

The specificity of the unusual flavobacterial glycuronidases that act on disaccharides containing delta4,5-unsaturated uronic acids was reinvestigated. The results show that the enzyme that hydrolyses the uronidic bond in disaccharides from hyaluronic acid and the chondroitin sulphates appears to be mainly specific for beta-D-(1 leads to 3)-derived linkages. The enzyme that hydrolyses the uronidic bond in a variety of disaccharides obtained from heparan sulphate and heparin appears to be specific for beta-D-(1 leads to 4)- and alpha-L-(1 leads to 4)- derived linkages. Thus the glycuronidases seem to be specific for linkage position rather than anomeric configuration, as had been thought previously. In addition, the data confirm other evidence that the major glucuronidic linkages in heparan sulphate and heparin have the beta-D-configuration, and the iduronidic linkages the alpha-L-configuration.
Comprehensive atlas of transplantation (2005)

* Multi-organ procurement from the cadaver donor (Davis/Kuo) * Principles of organ preservation * Heart * Lung * Liver * Pancreas * Heart transplantation (Davis) * Cadaver recipient operation * Lung transplantation (Davis) * Cadaver * Recipient operation * Single lung * Double lung * Living donor * Donor operation * Recipient operation * Liver transplantation (Kuo) * Cadaver Recipient operation * Adult (piggyback, VVB, caval interposition) (Kuo) * Living donor * Donor operation * Adult Right-to-Adult (LBJ) * Adult Left lateral-to-Ped (Jeff L, Amy L) * Recipient operation * Adult (LBJ) * Pediatric (Jeff L.) * Kidney transplantation (Dafoe/Bollinger) * Cadaver * Recipient operation (Bollinger) * Adult * Pediatric en-bloc * Pancreas transplantation (Dafoe) * Cadaver Pancreas
Molecular and Biochemical Characterization of 2-Hydroxyisoflavanone Dehydratase. Involvement of Carboxylesterase-Like Proteins in Leguminous Isoflavone Biosynthesis (2005)

Isoflavonoids are ecophysiologically active secondary metabolites of the Leguminosae and known for health-promoting phytoestrogenic functions. Isoflavones are synthesized by 1,2-elimination of water from 2-hydroxyisoflavanones, the first intermediate with the isoflavonoid skeleton, but details of this dehydration have been unclear. We screened the extracts of repeatedly fractionated Escherichia coli expressing a Glycyrrhiza echinata cDNA library for the activity to convert a radiolabeled precursor into formononetin (7-hydroxy-4'-methoxyisoflavone), and a clone of 2-hydroxyisoflavanone dehydratase (HID) was isolated. Another HID cDNA was cloned from soybean (Glycine max), based on the sequence information in its expressed sequence tag library. Kinetic studies revealed that G. echinata HID is specific to 2,7-dihydroxy-4'-methoxyisoflavanone, while soybean HID has broader specificity to both 4'-hydroxylated and 4'-methoxylated 2-hydroxyisoflavanones, reflecting the structures of isoflavones contained in each plant species. Strikingly, HID proteins were members of a large carboxylesterase family, of which plant proteins form a monophyletic group and some are assigned defensive functions with no intrinsic catalytic activities identified. Site-directed mutagenesis with soybean HID protein suggested that the characteristic oxyanion hole and catalytic triad are essential for the dehydratase as well as the faint esterase activities. The findings, to our knowledge, represent a new example of recruitment of enzymes of primary metabolism during the molecular evolution of plant secondary metabolism.
3D structure of the influenza virus polymerase complex: Localization of subunit domains (2003)

The 3D structure of the influenza virus polymerase complex was determined by electron microscopy and image processing of recombinant ribonucleoproteins (RNPs). The RNPs were generated by in vivo amplification using cDNAs of the three polymerase subunits, the nucleoprotein, and a model virus-associated RNA containing 248 nt. The polymerase structure obtained is very compact, with no apparent boundaries among subunits. The position of specific regions of the PB1, PB2, and PA subunits was determined by 3D reconstruction of either RNP-mAb complexes or tagged RNPs. This structural model is available for the polymerase of a negative-stranded RNA virus and provides a general delineation of the complex and its interaction with the template-associated nucleoprotein monomers in the RNP.
Probiotics and Intestinal Colonization by Vancomycin-Resistant Enterococci in Mice and Humans (2010)

We investigated the impact of probiotics on the intestinal carriage of vancomycin-resistant enterococci (VRE). Administration of Lactobacillus rhamnosus Lcr35 but not Escherichia coli Nissle reduced, although not significantly, the density of VRE colonization in a murine model. No effect of Lcr35 was observed in a double-blind placebo randomized study, involving nine patients.
Erlotinib in the treatment of non-small cell lung cancer: current status and future developments. (2010)

Erlotinib is an orally small molecule inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR). Currently, erlotinib, at a standard oral daily dose of 150 mg, is licensed for the treatment of unselected recurrent non-small cell lung cancer (NSCLC) patients, however, it is being investigated in all stages of NSCLC. Erlotinib is well tolerated, with common toxicities including rash and diarrhoea. The optimization of the therapeutic impact of erlotinib in NSCLC will be more defined when reliable predictive factors are identified. An important step has been made in the molecular characterization of potentially sensitive NSCLC patients. In fact, we have learned that activation, somatic EGFR gene mutations within the tyrosine kinase domain, are associated with a high possibility of a long lasting therapeutic response to erlotinib. The present review discusses the role of erlotinib in the treatment of NSCLC.
Structure/function studies of human immunodeficiency virus type 1 reverse transcriptase. Alanine scanning mutagenesis of an alpha-helix in the thumb subdomain. (1994)

Human immunodeficiency virus type 1 reverse transcriptase has subunits of 66 and 51 kDa (p66 and p51, respectively). Structural studies indicate that each subunit consists of common subdomains. The polymerase domain of p66 forms a nucleic acid binding cleft, and, by analogy with a right hand, the subdomains are referred to as fingers, palm, and thumb (Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A., and Steitz, T. A. (1992) Science 256, 1783-1790). Residues 257-266 correspond to a highly conserved region of primary structure among retroviral pol genes. Crystallographic evidence indicates that these residues are in the thumb subdomain and form part of an alpha-helix (alpha H), which interacts with DNA (Jacobo-Molina, A., Ding, J., Nanni, R. G., Clark, A. D., Jr., Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., Clark, P., Hizi, A., Hughes, S. H., and Arnold, E. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 6320-6324). To define the role of this region during catalytic cycling, we performed systematic site-directed mutagenesis from position 253 through position 271 by changing each residue, one by one, to alanine. Each mutant protein was expressed and purified, and their substrate-specific activities were surveyed. The results are consistent with alpha H (residues 255-268) of p66 interacting with the template and/or primer strand. The core of alpha H appears to play an important role in template-primer binding (residues Gln-258, Gly-262, and Trp-266), and in protein-protein interactions (residues Val-261 and Leu-264). The periodicity of the effects observed suggest that a segment of one face of alpha H interacts with the template-primer. The lower fidelity observed with alanine mutants of Gly-262 and Trp-266 correlated with an over 200-fold increase in the dissociation rate constant for template-primer relative to wild type enzyme and suggests that enzyme-DNA interactions in the template-primer stem are important fidelity determinants.
O-GLYCBASE version 2.0: a revised database of O-glycosylated proteins (1997)

O-GLYCBASE is an updated database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the literature, and from the SWISS-PROT database. Entries include information about species, sequence, glycosylation sites and glycan type. O-GLYCBASE is now fully cross-referenced to the SWISS-PROT, PIR, PROSITE, PDB, EMBL, HSSP, LISTA and MIM databases. Compared with version 1.0 the number of entries have increased by 34%. Revision of the O-glycan assignment was performed on 20% of the entries. Sequence logos displaying the acceptor specificity patterns for the GalNAc, mannose and GlcNAc transferases are shown. The O-GLYCBASE database is available through WWW or by anonymous FTP.