gebhart/patrepeval huggingface dataset:
Yeast forward and reverse 'n'-hybrid systems (1999)

Since its original description almost 10 years ago, the yeast two-hybrid system has been used extensively to identify protein-protein interactions from many different organisms. Simultaneously, a number of 'variations on a theme' based on the original concept have been described. In one set of variations, systems were developed to detect other macromolecular interactions: DNA-protein (one-hybrid), RNA-protein (RNA-based three-hybrid) and small molecule-protein interactions (ligand-based three-hybrid). These different versions are collectively referred to here as 'n-hybrid systems'. In another set of variations, the original configuration of the two-hybrid fusion proteins was modified to expand the range of possible protein-protein interactions that could be analyzed. For example, systems were developed to detect trimeric interactions, ligand-receptor interactions or interactions that require particular post-translational modifications. Finally, the original concept was turned upside down and 'reverse n-hybrid systems' were developed to identify mutations, peptides or small molecules that dissociate macromolecular interactions. These reagents can be used to validate, in the relevant biological systems, the potential interactions identified with the 'forward n-hybrid systems'. The powerful genetic selections of the forward and reverse n-hybrid systems are proving useful in proteomic projects aimed at generating macromolecular interaction maps.
Novel Approaches for Targeted Cancer Therapy (2004)

The clinical use of chemotherapeutic agents against malignant tumors is successful in many cases but suffers from major drawbacks. One drawback is lack of selectivity, which leads to severe side effects and limited efficacy; and another is the emergence/selection of drug-resistance. To limit non-specific toxicity and to improve the efficiency of cancer therapy, "tumor markers", which are proteins generally overexpressed on the surface of tumor cells, can be selectively targeted. Growth factor receptors are one of the most extensively studied tumor markers. The implication of growth factor receptors in the pathogenesis and evolution of cancer has clearly been established and therefore, provides a rationale for therapeutic intervention. The targeting of cytotoxic substances to tumor markers with "magic bullets" is an old idea that raised high expectations but also disappointment. Over the past decade, newly gained understanding of mechanisms for targeted therapy have brought new hopes. Pharmacological agents that selectively target and block the action of growth factors and their receptors have been attempted, such as monoclonal antibodies (mAbs) (whole molecule or fragments), bispecific antibodies, mAbs conjugated to drugs, toxins or radioisotopes, small peptidic and peptidomimetic molecules in free form or conjugated to drugs, anti-sense oligonucleotides, immunoliposomes-encapsulated drugs, and small molecule inhibitors. This review will focus on current developments of selective targeting and bypassing drug resistance in the management of growth factor receptor-overexpressing tumors.
[Changes in Toll-like receptor 2 and 4 gene expression in vital organs in septic rats and their regulation mechanisms]. (2003)

These data suggest that severe peritoneal infection could result in up-regulation of TLR2/4 mRNA expression in vital organs, which might play important roles in mediating proinflammatory cytokine synthesis and release. Endotoxemia appears to be involved in the activation of tissue TLR2/4 expression associated with CLP-induced sepsis.
Organic Carbonates (1996)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganic Carbonates†Abbas-Alli G. Shaikh and Swaminathan SivaramView Author Information Department of Chemical Sciences, North Maharashtra University, Jalgaon 425 001, India Division of Polymer Chemistry, National Chemical Laboratory, Pune 411 008, IndiaCite this: Chem. Rev. 1996, 96, 3, 951–976Publication Date (Web):May 9, 1996Publication History Received30 June 1995Revised27 February 1996Published online9 May 1996Published inissue 1 January 1996https://doi.org/10.1021/cr950067iCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views13037Altmetric-Citations1222LEARN 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 InReddit Read OnlinePDF (379 KB) Get e-AlertscloseSUBJECTS:Alkyls,Aromatic compounds,Catalysts,Hydrocarbons,Inorganic carbon compounds Get e-Alerts
Structure based design of protein linkers for zinc finger nuclease (2013)

Zinc finger nucleases are a promising tool to edit DNA in many biological applications, in particular for gene knockout. Despite many efforts the number of genes that can be effectively targeted with ZFNs remains severely limited, as available constructs cannot address arbitrary gene sequences. Here, we develop a novel concept to significantly enhance the number of DNA sequences that can be targeted by ZFN. Using an efficient computational model, we provide an extensive library of possible linker molecules between individual zinc finger motifs in the construct that can skip up to 10 base pairs between adjacent zinc finger recognition sites in the DNA sequence, which increases the number of genes that can be efficiently targeted by more than an order of magnitude.
Immunohistochemical identification of thrombospondin in normal human brain and in Alzheimer's disease. (1992)

Thrombospondin is part of a family of adhesive glycoproteins and is involved in a number of physiologic processes such as angiogenesis and neurite outgrowth. Immunohistochemical localization of thrombospondin in normal human brains was investigated in the hippocampus and inferior temporal cortex. Two antibodies (one polyclonal and one monoclonal) against thrombospondin-labeled microvessels, glial cells, and a subpopulation of pyramidal neurons. The distribution of thrombospondin staining in patients with Alzheimer's disease was found to be comparable to control subjects. However, in patients with Alzheimer's disease a subset of pyramidal neurons that may be vulnerable in Alzheimer's disease exhibited decreased staining. This decrease in the intensity of labeling might constitute a marker for a neuronal population prone to early degeneration. In addition, thrombospondin staining was demonstrated in senile plaques in Alzheimer's disease. These results suggest that thrombospondin may be involved in the process of neuronal degeneration and senile plaque formation.
Insight into Asphaltene Nanoaggregate Structure Inferred by Small Angle Neutron and X-ray Scattering (2011)

Complementary neutron and X-ray small angle scattering results give prominent information on the asphaltene nanostructure. Precise SANS and SAXS measurements on a large q-scale were performed on the same dilute asphaltene-toluene solution, and absolute intensity scaling was carried out. Direct comparison of neutron and X-ray spectra enables description of a fractal organization made from the aggregation of small entities of 16 kDa, exhibiting an internal fine structure. Neutron contrast variation experiments enhance the description of this nanoaggregate in terms of core-shell disk organization, giving insight into core and shell dimensions and chemical compositions. The nanoaggregates are best described by a disk of total radius 32 Å with 30% polydispersity and a height of 6.7 Å. Composition and density calculations show that the core is a dense and aromatic structure, contrary to the shell, which is highly aliphatic. These results show a good agreement with the general view of the Yen model (Yen, T. F.; et al. Anal. Chem.1961, 33, 1587-1594) and as for the modified Yen model (Mullins, O. C. Energy Fuels2010, 24, 2179-2207), provide characteristic dimensions of the asphaltene nanoaggregate in good solvent.
Targeted mutation detection in breast cancer using MammaSeq™ (2019)

In solid tumor biopsies and ctDNA, MammaSeq detects clinically actionable mutations (OncoKB levels 1-3) in 22/46 (48%) solid tumors and in 4/14 (29%) of ctDNA samples. MammaSeq is a targeted panel suitable for clinically actionable mutation detection in breast cancer.
Europe PMC: a full-text literature database for the life sciences and platform for innovation (2014)

This article describes recent developments of Europe PMC (http://europepmc.org), the leading database for life science literature. Formerly known as UKPMC, the service was rebranded in November 2012 as Europe PMC to reflect the scope of the funding agencies that support it. Several new developments have enriched Europe PMC considerably since then. Europe PMC now offers RESTful web services to access both articles and grants, powerful search tools such as citation-count sort order and data citation features, a service to add publications to your ORCID, a variety of export formats, and an External Links service that enables any related resource to be linked from Europe PMC content.
Structure validation by Cα geometry: ϕ,ψ and Cβ deviation (2003)

Geometrical validation around the Calpha is described, with a new Cbeta measure and updated Ramachandran plot. Deviation of the observed Cbeta atom from ideal position provides a single measure encapsulating the major structure-validation information contained in bond angle distortions. Cbeta deviation is sensitive to incompatibilities between sidechain and backbone caused by misfit conformations or inappropriate refinement restraints. A new phi,psi plot using density-dependent smoothing for 81,234 non-Gly, non-Pro, and non-prePro residues with B < 30 from 500 high-resolution proteins shows sharp boundaries at critical edges and clear delineation between large empty areas and regions that are allowed but disfavored. One such region is the gamma-turn conformation near +75 degrees,-60 degrees, counted as forbidden by common structure-validation programs; however, it occurs in well-ordered parts of good structures, it is overrepresented near functional sites, and strain is partly compensated by the gamma-turn H-bond. Favored and allowed phi,psi regions are also defined for Pro, pre-Pro, and Gly (important because Gly phi,psi angles are more permissive but less accurately determined). Details of these accurate empirical distributions are poorly predicted by previous theoretical calculations, including a region left of alpha-helix, which rates as favorable in energy yet rarely occurs. A proposed factor explaining this discrepancy is that crowding of the two-peptide NHs permits donating only a single H-bond. New calculations by Hu et al. [Proteins 2002 (this issue)] for Ala and Gly dipeptides, using mixed quantum mechanics and molecular mechanics, fit our nonrepetitive data in excellent detail. To run our geometrical evaluations on a user-uploaded file, see MOLPROBITY (http://kinemage.biochem.duke.edu) or RAMPAGE (http://www-cryst.bioc.cam.ac.uk/rampage).
Metabolic interactions between mibefradil and HMG‐CoA reductase inhibitors: an in vitro investigation with human liver preparations (1999)

Mibefradil, at therapeutically relevant concentrations, strongly suppressed the metabolism in human liver microsomes of simvastatin, lovastatin, atorvastatin and cerivastatin through its inhibitory effects on CYP3A4/5, while the effects of mibefradil on fluvastatin, a substrate for CYP2C8/9, were minimal in this system. Since mibefradil is a potent mechanism-based inhibitor of CYP3A4/5, it is anticipated that clinically significant drug-drug interactions will likely ensue when mibefradil is coadministered with agents which are cleared primarily by CYP3A-mediated pathways.
The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. (1993)

A method using PCR amplification and primer extension with fluorescent oligonucleotides was developed to analyze T-cell repertoires. The sizes of the hypervariable CDR3-like regions of the murine T-cell antigen receptor beta chains were measured for all possible V beta-J beta combinations. This analysis shows that beta chains are distributed into at least 2000 groups, a value that provides a lower limit to their complexity. The CDR3 sizes appear to be dependent on the J beta and especially the V beta segment used and correlates with amino acid sequence motifs in the corresponding CDR1 region. This feature of T-cell receptors is discussed.
A GFP‐based screen for growth‐arrested, recombinant protein‐producing cells (2002)

The growth of anchorage-dependent Chinese hamster ovary (CHO) cells is arrested upon serum deprivation; however, a portion of these cells remain viable for extended time periods in serum-free culture. This work presents a strategy to both rapidly generate a heterogeneous population of CHO cells as well as to select for subpopulations that remain robust and continue to produce recombinant protein when their growth is arrested. Stable expression of recombinant proteins in mammalian cells is often a tedious and time-consuming process because only a small percentage of transfected cells will express sufficient quantities of protein. To overcome the limitations associated with standard transformation and selection methods, bicistronic retroviral expression technology was used. First, bicistronic retroviral constructs encoding for both interferon gamma (IFN-gamma), the model therapeutic protein, and green fluorescent protein (GFP), the quantitative selectable marker, were generated. Next, recombinant retroviruses were obtained from transient transfection of a helper-cell line and were used to infect susceptible CHO cells. Cells with the bicistronic expression module stably integrated into their genome fluoresce green and could thereby be easily isolated by fluorescence-activated cell sorting. Upon subjecting successfully infected cells to serum withdrawal, significant declines in cell viability and GFP expression occurred. After imposing this selection pressure on the cells for 8 days, GFP producers were isolated from the survivors by fluorescence-activated cell sorting and expanded. To evaluate the effectiveness of the screening process, the selected cells were exposed to a second round of serum deprivation. Unlike the original cell population from which it was derived, the subpopulation remained robust and continued to stably express both GFP and IFN-gamma throughout the extended period of serum-free culture. Within 2 weeks, cells selected for recombinant protein production under serum-free conditions were successfully generated and isolated.
Chemical synthesis and immunological activities of glycolipids structurally related to lipid A (1985)

Complete chemical syntheses of a number of monosaccharides derived from 2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-D-glucopyranose and structurally related to the hydrophobic moiety (lipid A) of several bacterial endotoxins are described. Selected humoral (complement activation) and cellular (mitogenicity and induction of interleukin 1 production) in vitro activities of a lipid A preparation obtained from the Bordetella pertussis endotoxin were compared with those of ten of these monosaccharides and with those of previously synthesized, analogous disaccharides. Results show that each of these in vitro activities of the lipid A preparation can be efficiently induced by at least one of the monosaccharide derivatives.
Triclosan Enhances the Clearing of Pathogenic Intracellular Salmonella or Candida albicans but Disturbs the Intestinal Microbiota through mTOR-Independent Autophagy (2018)

Triclosan (TCS) is a broad-spectrum antimicrobial agent, whose well-known antibacterial mechanism is inhibiting lipid synthesis. Autophagy, an innate immune response, is an intracellular process that delivers the cargo including pathogens to lysosomes for degradation. In this study, we first demonstrated that TCS induced autophagy in a dose-dependent manner in non-phagocytic cells (HeLa) and in macrophages (Raw264.7) and <i>in vivo</i>. The western blot results also revealed that TCS induced autophagy via the AMPK/ULK1 and JNK/ERK/p38 pathways independent of mTOR. The immunofluorescence results indicated that TCS up-regulated the expression of the ubiquitin receptors NDP52 and p62 and strengthened the co-localization of these receptors with <i>Salmonella enterica</i> Typhimurium (<i>S</i>. typhimurium) or <i>Candida albicans</i> (<i>C. albicans</i>) in infected MΦ cells. In addition, sub-lethal concentrations of TCS enhanced the clearing of the pathogens <i>S</i>. typhimurium or <i>C. albicans</i> in infected MΦ and in corresponding mouse infection models <i>in vivo</i>. Specifically, we found that a sub-inhibitory concentration of TCS induced autophagy, leading to an imbalance of the intestinal microflora in mice through the analysis of 16s rRNA Sequencing. Together, these results demonstrated that TCS induced autophagy, which enhanced the killing against pathogenic <i>S</i>. typhimurium or <i>C. albicans</i> within mammal cells but broke the balance of the intestinal microflora.
Correlation between cellulose binding and activity of cellulose‐binding domain mutants of Humicola grisea cellobiohydrolase 1 (2007)

The cellulose-binding domains (CBDs) of fungal cellulases interact with crystalline cellulose through their hydrophobic flat surface formed by three conserved aromatic amino acid residues. To analyze the functional importance of these residues, we constructed CBD mutants of cellobiohydrolase 1 (CBH1) of the thermophilic fungus Humicola grisea, and examined their cellulose-binding ability and enzymatic activities. High activity on crystalline cellulose correlated with high cellulose-binding ability and was dependent on the combination and configuration of the three aromatic residues. Tyrosine works best in the middle of the flat surface, while tryptophan is the best residue in the two outer positions.
Cancer stem cells and resistance to chemo and radio therapy (2011)

Cancer stem cells (CSCs, or tumor initiating cells) are responsible for tumor initiation. If cancer treatment kills most of cancer cells in the stage of transit amplifying and differentiation without killing the stem cells, the surviving CSCs will eventually lead to recurrence of tumors. Studies have suggested that CSCs may be the primary mediators of resistance to chemo- and radio-therapy, leading to failure in cancer therapy. Numerous targets are being investigated for their potential involvement in the self-renewal and chemo- and radio-resistance of cancer cells. However, despite the intensive efforts invested into characterizing the role of cancer stem cells, there is a sense of uncertainty regarding the identity and number of these cells as well as the implications in cancer treatment. In this review, we will discuss the identification of CSCs by cell surface markers, the biology of CSCs, and the role of CSCs in resistance to radio- and chemo-therapy. This review will discuss the advances in targeting CSCs to improve the efficacy of chemo- and radio-therapy.
Influence of the <italic>A<sup>y</sup></italic> Gene on Mammary-Gland Tumors, Hepatomas, and Normal Growth in Mice (1961)

Hybrid (C3H × Y)F1 mice that were genetically uniform except for segregation at the agouti locus (1/2 AyA, yellow, and 1/2 Aa, agouti) were studied in respect to body size, occurrence of mammary tumors in the females, and occurrence of hepatomas in the males. An effect of Ay increasing susceptibility to mammary tumors was noted in the age at which the tumors arose in the virgin females. The average tumor age of the Aa virgins was 15 months while that of the AyA virgins was only 8 months. Breeding eliminated this difference, for the average tumor age in both genotypic groups of breeders was 8 months. The final incidence in all 4 groups was or approximated 100 percent. In addition to adenocarcinomas of type A or type B there was a distinct group of a type rarely seen in other strains or hybrids that has been designated as adenocarcinoma, type Y. All but one of those of this type occurred in breeders. Ay increased susceptibility to spontaneous hepatomas in the males. The incidence in both genotypic groups was high, but it was higher in the AyA males than in the Aa males, and the AyA males had a significantly higher average number of hepatomas than the Aa males. Males treated with CCl4 failed to show any carcinogenic effect of this compound in increasing occurrence of hepatomas in these susceptible hybrids, and the Ay gene did not significantly increase the occurrence of hepatomas in these treated males. Ay increased body weight by approximately 10 g in the males and approximately 15 g in the females; it significantly increased total-body length in both males and females, and it significantly increased weight of gastrocnemius muscle in the females. In the combined genotypic groups of males, a significant positive correlation was found between number of spontaneous hepatomas and body weight, total-body length, and length of femur. Relationships between normal growth and neoplasia are discussed.
Synthesis of polypropylene-graft-poly(methyl methacrylate) copolymers by the borane approach (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of polypropylene-graft-poly(methyl methacrylate) copolymers by the borane approachT. C. Chung, D. Rhubright, and G. J. JiangCite this: Macromolecules 1993, 26, 14, 3467–3471Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://doi.org/10.1021/ma00066a001RIGHTS & PERMISSIONSArticle Views786Altmetric-Citations86LEARN 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 InReddit PDF (1 MB) Get e-Alerts Get e-Alerts