gebhart/patrepeval huggingface dataset:
The Gastrointestinal Tract Microbiome and Potential Link to Alzheimerâ€™s Disease (2014)

OPINION article Front. Neurol., 04 April 2014Sec. Epilepsy https://doi.org/10.3389/fneur.2014.00043
Sanguinarine Biosynthesis Is Associated with the Endoplasmic Reticulum in Cultured Opium Poppy Cells after Elicitor Treatment (2005)

Three key benzylisoquinoline alkaloid biosynthetic enzymes, (S)-N-methylcoclaurine-3'-hydroxylase (CYP80B1), berberine bridge enzyme (BBE), and codeinone reductase (COR), were localized in cultured opium poppy (Papaver somniferum) cells by sucrose density gradient fractionation and immunogold labeling. CYP80B1 catalyzes the second to last step in the formation of (S)-reticuline, the last common intermediate in sanguinarine and morphine biosynthesis. BBE converts (S)-reticuline to (S)-scoulerine as the first committed step in sanguinarine biosynthesis, and COR catalyzes the penultimate step in the branch pathway leading to morphine. Sanguinarine is an antimicrobial alkaloid that accumulates in the vacuoles of cultured opium poppy cells in response to elicitor treatment, whereas the narcotic analgesic morphine, which is abundant in opium poppy plants, is not produced in cultured cells. CYP80B1 and BBE were rapidly induced to high levels in response to elicitor treatment. By contrast, COR levels were constitutive in the cell cultures, but remained low and were not induced by addition of the elicitor. Western blots performed on protein homogenates from elicitor-treated cells fractionated on a sucrose density gradient showed the cosedimentation of CYP80B1, BBE, and sanguinarine with calreticulin, and COR with glutathione S-transferase. Calreticulin and glutathione S-transferase are markers for the endoplasmic reticulum (ER) and the cytosol, respectively. In response to elicitor treatment, large dilated vesicles rapidly developed from the lamellar ER of control cells and fused with the central vacuole. Immunogold localization supported the association of CYP80B1 and BBE with ER vesicles, and COR with the cytosol in elicitor-treated cells. Our results show that benzylisoquinoline biosynthesis and transport to the vacuole are associated with the ER, which undergoes major ultrastructural modification in response to the elicitor treatment of cultured opium poppy cells.
Effect of pH on the growth and glucose metabolism of Neisseria gonorrhoeae (1978)

This study examined the effect of pH on the metabolism of glucose by Neisseria gonorrhoeae. Radiorespirometric studies revealed that cells growing at pH 7.2 or 8.0 metabolized glucose primarily (ca. 80%) via the Entner-Doudoroff pathway. The remainder of the glucose was metabolized via the pentose phosphate pathway (ca. 20%). The tricarboxylic acid cycle was not active during glucose catabolism at either pH 7.2 or 8.0, and acetate accumulated in the medium. Cells growing at pH 6.0 had markedly increased pentose phosphate pathway activity (ca. 50%) and a functioning tricarboxylic acid cycle. The alteration in pathways was not due to differences in growth rate, but to the pH of the medium. Chemical fractionation of labeled cells and total hexose analyses revealed that growth pH markedly affected the composition of the gonococcus.
Family environment, expressed emotion and adolescent self-harm: A review of conceptual, empirical, cross-cultural and clinical perspectives (2012)

Self-harm in young people is a complex and pervasive problem with a number of co-existing risk factors. Although research has implicated a range of family variables in understanding the onset, maintenance and prevention of adolescent self-harm, relatively little attention has been given to the expressed emotion (EE) construct. Based on a narrative review and synthesis of peer-reviewed literature up to and including 2011, this paper considers the conceptual background and empirical evidence for the role of family environment in the expression of adolescent self-harm, with a particular focus on EE. The clinical implications of this literature for working with young people and families from different cultures are also addressed. In summary, the surveyed research provides insufficient evidence for a direct causal link between family environment and adolescent self-harm, with questions raised about the temporal sequencing of measured variables, specificity of implicated family risk factors, and the nature and role of protective factors in families. Emerging evidence for an association between high EE and adolescent self-harm requires replication in well-controlled, prospective studies. There is also a lack of empirically-supported, family-based treatment modalities for adolescents who self-harm. Intervention strategies should be guided by personalised formulation, taking into account individual vulnerabilities, strengths and social contexts, as well as cultural norms for family environment.
On the performance of an oversampled analog to digital converter with digital requantizer in feedback path (1991)

Conventional delta-sigma converters limit the complexity of the feedback DAC to a precision single bit which in turn leads to the use of a 1-bit ADC in the feedforward path. A spectrally controlled requantization between the output of the multibit ADC and the input to the 1-bit DAC can be performed with an oversampled digital sigma-delta loop in the feedback path of the analog sigma-delta loop. This paper we describes and reports on the hardware implementation of an enhanced performance delta-sigma loop modified to use a multibit ADC in the feedforward path along with a 1-bit DAC in the feedback path.
KRAS Mutations and Susceptibility to Cetuximab and Panitumumab in Colorectal Cancer (2009)

Recent retrospective evidence from several randomized studies has established that advanced colorectal cancer patients with tumors harboring a mutation in the KRAS gene do not derive benefit from the administration of epidermal growth factor receptor-directed monoclonal antibodies, such as cetuximab or panitumumab. This represents a paradigm-changing event and will have substantial impact on current and future anticancer drug development. These results add to the economic and ethical considerations involved in the development of novel targeted therapies and should increase our scrutiny of mechanisms of resistance and predictive biomarkers while in earlier developmental stages. In this article, we will review the available clinical data and discuss the implications for future drug development in colorectal cancer.
The Safety of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Trastuzumab in HER-2/neu Overexpressed/Amplified Breast Cancer (2008)

Dose-dense AC followed by P/T followed by T is feasible and is not likely to increase the incidence of cardiac events compared to established regimens.
Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes (2002)

The metabolic detoxification capacity may critically regulate the susceptibility of human tissues to cancer development. We used standardized and quantitative, reverse transcription-polymerase chain reaction (StaRT-PCR) and microarray chip techniques to analyze transcript levels of multiple detoxification enzymes in cultured normal human oral keratinocytes (NOK) and the Siman virus 40 T antigen-immortalized oral keratinocyte line SVpgC2a, viewing the latter as a model of a benign tumor state. With good agreement between the 2 methodologies, NOK and SVpgC2a were found to express transcripts for cytochrome P450 enzymes (CYPs), factors related to CYP induction and enzymes involved in conjugation reactions or detoxification of reactive oxygen. The cell types expressed similar levels of CYP 2B6/7, CYP 2E1, P450 oxidoreductase, the aryl hydrocarbon receptor nuclear translocator, sulfotransferase 1A1, sulfotransferase 1A3, epoxide hydrolase, glutathione S-transferase M3, glutathione S-transferase pi and catalase, superoxide dismutase 1, glutathione peroxidase 1 and glutathione peroxidase 3. In contrast, SVpgC2a exhibited comparatively higher levels of CYP1A1, 1B1, aryl hydrocarbon receptor, glutathione S-transferase M1, 2, 4, 5, glutathione S-transferase theta 1 and superoxide dismutase 2 and comparatively lower levels of UDP glycosyltransferase 2 and microsomal glutathione S-transferase 1. Some transcripts, e.g., CYP 2A6/7, were not detected by either standard, non quantitative RT-PCR or the above methods, whereas others were barely quantifiable by StaRT-PCR, i.e., were present at 1-10 molecules/10(6) molecules of actin. Overall, the expression analysis demonstrated presence of mRNA for multiple enzymes involved in foreign compound metabolism and detoxification pathways, including several enzymes not previously reported for oral epithelium. Generally, the comparison of NOK from 2 individuals indicated relatively similar transcript levels of these enzymes. In contrast, differences between NOK and SVpgC2a, e.g., for CYP1B1, may reflect alteration caused by immortalization and aid identification of early stage tumor markers in oral epithelium.
Receptor activator of nuclear factor-κB ligand and osteoprotegerin (2001)

Abnormalities of the RANKL/OPG system have been implicated in the pathogenesis of various primary and secondary bone malignancies. The systemic administration of OPG appears to be a potent novel therapeutic agent for treatment of these disorders.
Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus (2005)

The pandemic influenza virus of 1918-1919 killed an estimated 20 to 50 million people worldwide. With the recent availability of the complete 1918 influenza virus coding sequence, we used reverse genetics to generate an influenza virus bearing all eight gene segments of the pandemic virus to study the properties associated with its extraordinary virulence. In stark contrast to contemporary human influenza H1N1 viruses, the 1918 pandemic virus had the ability to replicate in the absence of trypsin, caused death in mice and embryonated chicken eggs, and displayed a high-growth phenotype in human bronchial epithelial cells. Moreover, the coordinated expression of the 1918 virus genes most certainly confers the unique high-virulence phenotype observed with this pandemic virus.
Interleukins 19, 20, and 24 Signal through Two Distinct Receptor Complexes (2002)

Cytokines that signal through Class II receptors form a distinct family that includes the interferons and interleukin 10 (IL-10). Recent identification of several IL-10 homologs has defined a cytokine subfamily that includes AK155, IL-19, IL-20, IL-22, and IL-24. Within this subfamily, IL-19, IL-20, and IL-24 exhibit substantial sharing of receptor complexes; all three are capable of signaling through IL-20RA/IL-20RB, and IL-20 and IL-24 both can also use IL-22R/IL-20RB. However, the biological effects of these three cytokines appear quite distinct: immune activity with IL-19, skin biology with IL-20, and tumor apoptosis with IL-24. To more fully elucidate their interactions with the receptor complexes, we have performed a series of in vitro assays. Reporter, proliferation, and direct STAT activation assays using cell lines expressing transfected receptors revealed differences between the receptor complexes. IL-19 and IL-24 also exhibited growth inhibition on a cell line endogenously expressing all three receptor subunits, an effect that was seen at cytokine levels two orders of magnitude above those required for STAT activation or proliferation. These results demonstrate that, although this subclass exhibits receptor complex redundancy, there are differences in ligand/receptor interactions and in signal transduction that may lead to specificity and a distinct biology for each cytokine.
Post-translational processing of Schizosaccharomyces pombe YPT5 protein. In vitro and in vivo analysis of processing mutants. (1993)

SpYPT5p is a member of the rab/YPT small GTP-binding protein family, which is believed to be involved in the regulation of intracellular trafficking. The protein sequence terminates with a CXC motif, and in our previous report (Newman, C. M. H., Giannakouros, T., Hancock, J. F., Fawell, E. H., Armstrong, J., and Magee, A. I. (1992) J. Biol. Chem. 267, 11329-11336) we have shown that SpYPT5p is prenylated both in vivo and in vitro, where geranylgeranylation was confirmed, and carboxyl-methylated. In order to dissect the role of prenylation of each cysteine, we have generated C-terminal mutants where either one or both cysteine(s) were replaced by serine and expressed them in vitro in reticulocyte lysates and in vivo in transfected COS cells. Our results suggest that both cysteines of the CXC motif are prenylated but that the rate of prenylation of the two cysteines is different. The upstream cysteine was found to be preferentially prenylated in reticulocyte lysates unless cytosol from COS cells was added. A separate activity could therefore be required for prenylation of the second cysteine, or the presence of an additional factor is needed to allow accumulation of doubly prenylated SpYPT5p. However, the modification of the upstream cysteine is not a prerequisite for the prenylation of the other. Furthermore, gene replacement in Schizosaccharomyces pombe revealed that each cysteine of the CXC motif can individually support function. Carboxyl methylation occurred only on protein which had been prenylated on the C-terminal cysteine and was required for efficient membrane binding in vitro.
Purification of a factor required for transcription of vaccinia virus early genes. (1988)

Partially purified DNA-dependent RNA polymerase from infectious vaccinia virus particles exhibits the following two activities: 1) specific transcription of double-stranded DNA templates containing vaccinia early promoters and 2) nonspecific transcription of single-stranded DNA templates. After further purification of the RNA polymerase, specific transcriptase activity was selectively diminished suggesting the loss of a transcription factor. In agreement with the latter hypothesis, transcriptase activity could be reconstituted by mixing the purified RNA polymerase with certain column fractions. A quantitative complementation assay was developed and used to locate the transcription factor during successive column chromatography steps. The factor eluted as a single peak of activity from single strand DNA-cellulose and phosphocellulose columns. An observation that the transcription factor binds specifically to vaccinia early promoter sequences was exploited in the final affinity chromatography steps. The purified factor was separated from all previously identified vaccinia enzymes and contained two polypeptides of Mr 77,000 and 82,000. A DNA-dependent ATPase activity also copurified with the transcription factor. Although a single template was used for assays during isolation, the purified factor stimulated transcription of three other early genes by 20-30-fold suggesting that it has a general role in conferring promoter specificity for initiation of early transcription.
Isolation, primary structure and synthesis of heat-stable enterotoxin produced by Yersinia enterocolitica (1985)

Five heat-stable enterotoxins were isolated from the culture supernatant of Yersinia enterocolitica and purified to homogeneity by DEAE-Sephacel and high-performance liquid chromatographies. They caused acute fluid accumulation in the intestine of suckling mice. The amino acid sequence of one of the enterotoxins was determined to be Ser-Ser-Asp-Trp-Asp-Cys-Cys-Asp-Val-Cys-Cys-Asn-Pro-Ala-Cys-Ala-Gly-Cys, by Edman degradation of its pyridylethylated derivative and a combination of fast atom bombardment mass spectrometry and carboxypeptidase B digestion. This structure was unambiguously confirmed by chemical synthesis. The other enterotoxins had longer or shorter amino acid sequences at their N termini, but the same sequence at their C termini. The six half-cystine residues formed intramolecular disulfide linkages, as shown by measurement of the molecular masses of the enterotoxins by fast atom bombardment mass spectrometry. The sequence of 13 amino acid residues at the C terminus showed similarity to those of heat-stable enterotoxins isolated from enterotoxigenic Escherichia coli [Aimoto, S. et al. (1982) Eur. J. Biochem. 129, 257-263; Takao, T. et al. (1983) FEBS Lett. 152, 1-5] suggesting that these similar sequences are related to the common biological and immunological properties of enterotoxins produced by Y. enterocolitica and enterotoxigenic E. coli.
Extracellular and Cytoplasmic Domains of Endoglin Interact with the Transforming Growth Factor-β Receptors I and II (2002)

Endoglin is an auxiliary component of the transforming growth factor-beta (TGF-beta) receptor system, able to associate with the signaling receptor types I (TbetaRI) and II (TbetaRII) in the presence of ligand and to modulate the cellular responses to TGF-beta1. Endoglin cannot bind ligand on its own but requires the presence of the signaling receptors, supporting a critical role for the interaction between endoglin and TbetaRI or TbetaRII. This study shows that full-length endoglin interacts with both TbetaRI and TbetaRII, independently of their kinase activation state or the presence of exogenous TGF-beta1. Truncated constructs encoding either the extracellular or the cytoplasmic domains of endoglin demonstrated that the association with the signaling receptors occurs through both extracellular and cytoplasmic domains. However, a more specific mapping revealed that the endoglin/TbetaRI interaction was different from that of endoglin/TbetaRII. TbetaRII interacts with the amino acid region 437-558 of the extracellular domain of endoglin, whereas TbetaRI interacts not only with the region 437-558 but also with the protein region located between amino acid 437 and the N terminus. Both TbetaRI and TbetaRII interact with the cytoplasmic domain of endoglin, but TbetaRI only interacts when the kinase domain is inactive, whereas TbetaRII remains associated in its active and inactive forms. Upon association, TbetaRI and TbetaRII phosphorylate the endoglin cytoplasmic domain, and then TbetaRI, but not TbetaRII, kinase dissociates from the complex. Conversely, endoglin expression results in an altered phosphorylation state of TbetaRII, TbetaRI, and downstream Smad proteins as well as a modulation of TGF-beta signaling, as measured by the reporter gene expression. These results suggest that by interacting through its extracellular and cytoplasmic domains with the signaling receptors, endoglin might affect TGF-beta responses.
Combined Oral Contraceptives in Women with Systemic Lupus Erythematosus (2005)

Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.
Pesticides and honey bees / (1981)

Honey bees produce honey and beeswax valued between $130 and $140 million annually.Much of this honey comes from cultivated crops.The annual value of crops benefited by insect pollination, most of which is performed by honey bees, ex- ceeds $10 billion.The farmer and the beekeeper are, therefore, de- pendent upon each other.Honey bees may be killed when crops are treated with pesticides.When this occurs, both the farmer and the beekeeper suffer a loss.For this reason, they need to cooperate fully in protecting the bees from pesticide damage.Observing the precautions recommended in this publication can greatly reduce bee losses from pes- ticide poisoning.Precautions for the Farmer• Use biological or other non- chemical control methods if at all possible.• If chemical control is essential, use the proper dosage of the safest material (on bees) that will give good pest control.
Origin of Activity in Cu-, Ru-, and Os-Mediated Radical Polymerization (2007)

A method is discussed for quantifying and categorizing the activity of an atom transfer radical polymerization (ATRP) catalyst as being derived from the product of its intrinsic reducing power and affinity for halide anions. The reducing power of several copper, ruthenium, and osmium ATRP catalysts was quantified with cyclic voltammetry in tetrahydrofuran, including for MtX2(PPh3)3, MtX(Cp*)PiPr3, and CuX(BPMODA) (where Mt = Ru and Os, X = Cl and Br, and BPMODA = N,N-bis(2-pyridylmethyl)octadecylamine). Spectrophotometric measurements were used to determine ATRP equilibrium constants (KATRP), a measure of catalyst polymerization activity. Ru and Os catalysts of activity comparable to that of Cu are ∼500 mV less reducing. Evaluation of kinetic polymerization data, together with E1/2 and KATRP values, allowed the determination that halide affinities of these Ru and Os compounds must be ∼7−9 orders of magnitude stronger than typical Cu ATRP catalysts to compensate for their comparatively poor reducing power. Additionally, the ability of the coordinatively unsaturated Os compounds to control polystyrene molecular weights under organometallic radical polymerization (OMRP) conditions where the Ru analogues and Cu compounds cannot is discussed in terms of the potential for Os to form stronger Mt−C bonds. DFT calculations, 1H NMR chain-end analyses, and polymer chain extensions were conducted in order to evaluate the likelihood that standard halogen atom transfer (for ATRP) and reversible radical trapping (for OMRP) processes are indeed regulating the growing radical concentrations under the respective appropriate conditions with the new Os catalysts.
Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. (1995)

Aspirin [acetylsalicylic acid (ASA)], along with its analgesic-antipyretic uses, is now also being considered for cardiovascular protection and treatments in cancer and human immunodeficiency virus infection. Although many of ASA's pharmacological actions are related to its ability to inhibit prostaglandin and thromboxane biosynthesis, some of its beneficial therapeutic effects are not completely understood. Here, ASA triggered transcellular biosynthesis of a previously unrecognized class of eicosanoids during coincubations of human umbilical vein endothelial cells (HUVEC) and neutrophils [polymorphonuclear leukocytes (PMN)]. These eicosanoids were generated with ASA but not by indomethacin, salicylate, or dexamethasone. Formation was enhanced by cytokines (interleukin 1 beta) that induced the appearance of prostaglandin G/H synthase 2 (PGHS-2) but not 15-lipoxygenase, which initiates their biosynthesis from arachidonic acid in HUVEC. Costimulation of HUVEC/PMN by either thrombin plus the chemotactic peptide fMet-Leu-Phe or phorbol 12-myristate 13-acetate or ionophore A23187 leads to the production of these eicosanoids from endogenous sources. Four of these eicosanoids were also produced when PMN were exposed to 15R-HETE [(15R)-15-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid] and an agonist. Physical methods showed that the class consists of four tetraene-containing products from arachidonic acid that proved to be 15R-epimers of lipoxins. Two of these compounds (III and IV) were potent inhibitors of leukotriene B4-mediated PMN adhesion to HUVEC, with compound IV [(5S,6R,15R)-5,6,15-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoi c acid; 15-epilipoxin A4] active in the nanomolar range. These results demonstrate that ASA evokes a unique class of eicosanoids formed by acetylated PGHS-2 and 5-lipoxygenase interactions, which may contribute to the therapeutic impact of this drug. Moreover, they provide an example of a drug's ability to pirate endogenous biosynthetic mechanisms to trigger new mediators.