gebhart/patrepeval huggingface dataset:
Cross-Referencing Eukaryotic Genomes: TIGR Orthologous Gene Alignments (TOGA) (2002)

Comparative genomics promises to rapidly accelerate the identification and functional classification of biologically important human genes. We developed the TIGR Orthologous Gene Alignment (TOGA; <http://www.tigr.org/tdb/toga/toga.shtml>) database to provide a cross-reference between fully and partially sequenced eukaryotic transcribed sequences. Starting with the assembled expressed sequence tag (EST) and gene sequences that comprise the 28 TIGR Gene Indices, we used high-stringency pair-wise sequence searches and a reflexive, transitive closure process to associate sequence-specific best hits, generating 32,652 tentative ortholog groups (TOGs). This has allowed us to identify putative orthologs and paralogs for known genes, as well as those that exist only as uncharacterized ESTs and to provide links to additional information including genome sequence and mapping data. TOGA provides an important new resource for the analysis of gene function in eukaryotes. In addition, an analysis of the most widely represented sequences can begin to provide insight into eukaryotic biological processes.
Selective GlyT1 Inhibitors: Discovery of [4-(3-Fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a Promising Novel Medicine To Treat Schizophrenia (2010)

The GlyT1 transporter has emerged as a key novel target for the treatment of schizophrenia. Herein, we report on the optimization of the 2-alkoxy-5-methylsulfonebenzoylpiperazine class of GlyT1 inhibitors to improve hERG channel selectivity and brain penetration. This effort culminated in the discovery of compound 10a (RG1678), the first potent and selective GlyT1 inhibitor to have a beneficial effect in schizophrenic patients in a phase II clinical trial.
Sites of Tau Important for Aggregation Populate β-Structure and Bind to Microtubules and Polyanions (2005)

The aggregation of the microtubule-associated tau protein and formation of "neurofibrillary tangles" is one of the hallmarks of Alzheimer disease. The mechanisms underlying the structural transition of innocuous, natively unfolded tau to neurotoxic forms and the detailed mechanisms of binding to microtubules are largely unknown. Here we report the high-resolution characterization of the repeat domain of soluble tau using multidimensional NMR spectroscopy. NMR secondary chemical shifts detect residual beta-structure for 8-10 residues at the beginning of repeats R2-R4. These regions correspond to sequence motifs known to form the core of the cross-beta-structure of tau-paired helical filaments. Chemical shift perturbation studies show that polyanions, which promote paired helical filament aggregation, as well as microtubules interact with tau through positive charges near the ends of the repeats and through the beta-forming motifs at the beginning of repeats 2 and 3. The high degree of similarity between the binding of polyanions and microtubules supports the hypothesis that stable microtubules prevent paired helical filament formation by blocking the tau-polyanion interaction sites, which are crucial for paired helical filament formation.
Selecting a mammalian species for the separation of X- and Y-chromosome-bearing spermatozoa (1979)

All (524) male karyotypes in An Atlas of Mammalian Chromosomes (Hsu & Benirschke, 1967-1977) were visually estimated for the chromatin difference between the X- and Y-chromosome-bearing spermatozoa. After more exact measurement of axial chromatid length for 100 karotypes, 24 species were found in which the difference between X and Y chromosomes was greater than 6.2%. It is suggested that such species would be the best for attempts to separate the X- and Y-bearing spermatozoa.
Granulysin-Derived Peptides Demonstrate Antimicrobial and Anti-Inflammatory Effects Against Propionibacterium acnes (2005)

Propionibacterium acnes is a key therapeutic target in acne, yet this bacterium has become resistant to standard antibiotic agents. We investigated whether the human antimicrobial protein granulysin is a potential candidate for the treatment of acne. Granulysin and synthetic granulysin-derived peptides possessing a helix-loop-helix motif killed P. acnes in vitro. Modification of a helix-loop-helix peptide, 31-50, by substitution of a tryptophan for the valine at amino acid 44 (peptide 31-50v44w) to increase its interaction with bacterial surfaces also increased its antimicrobial activity. Moreover, when synthesized with D- rather than L-type amino acids, this peptide (D-31-50v44w) became less susceptible to degradation by proteases and more effective in killing P. acnes. Granulysin peptides were bactericidal, demonstrating an advantage over standard bacteriostatic antibiotics in their control of P. acnes. Moreover, peptide D-31-50v44w killed P. acnes in isolated human microcomedone preparations. Importantly, peptides 31-50, 31-50v44w, and D-31-50v44w also have potential anti-inflammatory effects, as demonstrated by suppression of P. acnes-stimulated cytokine release. Taken together, these data suggest that granulysin peptides may be useful as topical therapeutic agents, providing alternatives to current acne therapies.
Characterization and sequence analysis of the scrA gene encoding enzyme IIScr of the Streptococcus mutans phosphoenolpyruvate-dependent sucrose phosphotransferase system (1989)

The Streptococcus mutans GS-5 scrA gene coding for enzyme IIScr of the phosphoenolpyruvate-dependent sucrose phosphotransferase system (PTS) was localized upstream from the scrB gene coding for sucrose-6-phosphate hydrolase activity after Mu dE transposon mutagenesis of plasmid pMH613. The cloned scrA gene product was identified as a 68-kilodalton protein by minicell analysis after isolation of the gene in plasmid pD4. In addition, the membrane fraction from Escherichia coli cells containing pD4 exhibited sucrose PTS activity upon complementation with enzyme I and HPr from strain GS-5. The nucleotide sequence of the scrA region revealed that this gene was located immediately upstream from the scrB gene and divergently transcribed from the opposite DNA strand. The scrA gene was preceded by potential Shine-Dalgarno and promoterlike sequences and was followed by a transcription terminator-like sequence. The scrA gene coded for an enzyme IIScr protein of 664 amino acid residues with a calculated molecular weight of 69,983. This enzyme IIScr protein was larger than the comparable proteins from Bacillus subtilis and E. coli containing sucrose-metabolizing plasmid pUR400. The 491-amino-acid N-terminal sequence of the S. mutans enzyme IIScr was homologous with the B. subtilis and E. coli sequences, and the 173-amino-acid C-terminal sequence of the S. mutans protein was also homologous with the Salmonella typhimurium enzyme IIIGlc and the 162-amino-acid C terminus of E. coli enzyme IIBgl. These results suggest that the sucrose PTS system of S. mutans is enzyme III independent.
Human papillomavirus DNA in uterine cervix squamous cell carcinoma and adenocarcinoma detected by polymerase chain reaction (1996)

HPV DNA was highly prevalent in both uterine cervix squamous cell carcinoma and adenocarcinoma. HPV16 was detected more often in squamous cell carcinoma and HPV18 was detected more often in adenocarcinoma. Both consensus structural L1 gene-derived primers and type-specific viral E6 oncogene-derived primers were necessary to detect HPV DNA in cervical carcinoma.
Using WordNet to turn a Folksonomy into a Hierarchy of Concepts. (2007)

As the volume of information in the read-write Web increases rapidly, folksonomies are becoming a widely used tool to organize and categorize resources in a bottom up, flat and inclusive way. However, due to their very structure, they show some drawbacks; in particular the lack of hierarchy bears some limitations in the possibilities of searching and browsing. In this paper we investigate a new approach, based on the idea of integrating an ontology in the navigation interface of a folksonomy, and we describe an application that filters del.icio.us keywords through the WordNet hierarchy of concepts, to enrich the possibilities of navigation.
Subthreshold Vicinal Diketone Levels in Lager Brewing Yeast Fermentations by Means of ILV5 Gene Amplification (1990)

Previous work on the haploid yeast Saccharomyces cerevisiae has demonstrated the positive role that ILV5 gene amplification plays in reducing vicinal diketone (VDK) levels in fermentations. The present work followed the same approach toward VDK reduction by amplification of the ILV5 gene product reductoisomerase in the lager brewing yeast Saccharomyces uvarum. The ILV5 gene was cloned into a 2μm-based plasmid using copper resistance as a selectable marker. Transformation and subsequent fermentations using European Brewing Convention tubes showed an increase in reductoisomerase activity and a 70–80% decrease in VDK levels throughout the course of the fermentations. Data collected also showed that fermentation capacity levels, growth rates, and flavor profiles were unaffected by increased ILV5 gene dosage.
High‐resolution analysis of DNA copy number alterations and gene expression in renal clear cell carcinoma (2007)

We analysed chromosomal copy number aberrations (CNAs) in renal cell carcinomas by array-based comparative genomic hybridization, using a genome-wide scanning array with 2304 BAC and PAC clones covering the whole human genome at a resolution of roughly 1.3 Mb. A total of 30 samples of renal cell carcinoma were analysed, including 26 cases of clear cell carcinoma (CCC) and four cases of chromophobe renal cell carcinoma (ChCC). In CCCs, gains of chromosomes 5q33.1-qter (58%), 7q11.22-q35 (35%) and 16p12.3-p13.12 (19%), and losses of chromosomes 3p25.1-p25.3 (77%), 3p21.31-p22.3 (81%), 3p14.1-p14.2 (77%), 8p23.3 (31%), 9q21.13-qter (19%) and 14q32.32-qter (38%) were detected. On the other hand, the patterns of CNAs differed markedly between CCCs and ChCCs. Next, we examined the correlation of CNAs with expression profiles in the same tumour samples in 22/26 cases of CCC, using oligonucleotide microarray. We extracted genes that were differentially expressed between cases with and without CNAs, and found that significantly more up-regulated genes were localized on chromosomes 5 and 7, where recurrent genomic gains have been detected. Conversely, significantly more down-regulated genes were localized on chromosomes 14 and 3, where recurrent genomic losses have been detected. These results revealed that CNAs were correlated with deregulation of gene expression in CCCs. Furthermore, we compared the patterns of genomic imbalance with histopathological features, and found that loss of 14q appeared to be a specific and additional genetic abnormality in high-grade CCC. When we compared the expression profiles of low-grade CCCs with those of high-grade CCCs, differentially down-regulated genes tended to be localized on chromosomes 14 and 9. Thus, it is suggested that copy number loss at 14q in high-grade CCC may be involved in the down-regulation of genes located in this region.
An overview of topoisomerase I-targeting agents. (1998)

The camptothecins are a new class of antitumor agents that target topoisomerase I. Irinotecan and topotecan are the most widely used camptothecin analogs in clinical practice, with documented clinical activity in colorectal and ovarian cancer. Ongoing clinical trials with these agents are further characterizing their spectra of clinical activity and determining their optimal schedule of administration in combination with other anticancer agents. Newer camptothecin analogs in clinical development, such as 9-aminocamptothecin, 9-nitrocamptothecin, GI1147211, and DX-8951f, are also being studied to determine if they have improved toxicity and efficacy profiles compared with existing analogs. The successful development of the camptothecins as antitumor agents demonstrates the importance of topoisomerase 1 as a target for cancer chemotherapy.
Nucteotide sequences of bovine αS1- andx-casein cDNAs (1984)

The nucleotide sequences corresponding to bovine alpha S1- and kappa-casein mRNAs are presented. An unusual alpha S1-casein cDNA has been characterised whose 5' end commences upstream from its putative TATA box. The alpha S1-casein mRNA is compared to rat alpha-casein mRNA and two components of divergence are identified. Firstly, the two sequences have diverged at a high point mutation rate and the rate of amino acid replacement by this mechanism is at least as great as the rate of divergence of any other part of the mRNAs. Secondly, the protein coding sequence has been subjected to several insertion/deletion events, one of which may be an example of exon shuffling . The kappa-casein mRNA sequence verifies the proposition that it has arisen from a different ancestral gene to the other caseins.
Shc products are substrates of erbB-2 kinase. (1993)

The shc genes encodes three widely expressed proteins of 46, 52 and 66 kDa. Overexpression of p46shc and p52shc in NIH3T3 fibroblasts induces a tumorigenic phenotype. Shc products are phosphorylated on tyrosine by the activated epidermal growth factor receptor (EGFR) and become physically associated with EGFR via their SH2 domain. Thus Shc oncoproteins may play a role in mitogenic signal transduction. Here we report that Shc products are substrates also of the erbB-2 kinase and form complexes with the erbB-2 product in intact cells. In vitro, the bacterially expressed Shc SH2 domain is sufficient to reconstitute the high affinity Shc/erbB-2 interaction. The erbB-2 region required for Shc binding was narrowed down to the most COOH-terminal 179 residues of gp185erbB-2; within this region, phosphorylation of one or more of the erbB-2 autophosphorylation sites is required for Shc/gp185erbB-2 complex formation as well as optimal phosphorylation of Shc products by the erbB-2 kinase. Thus, Shc proteins may play a role in signal transduction by gp185erbB-2.
Structural Analysis of Hybrid Titania-Based Mesostructured Composites (2005)

High-optical-quality titania-based mesostructured films with cubic or 2D-hexagonal symmetry were fabricated by combining trifluoroacetate (TFA)-modified titanium precursors with amphiphilic triblock poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) copolymers. The distribution, dynamics, and local environments of the TFA-modified titania, PEO, and PPO components of the hybrid were investigated. IR/Raman spectroscopy, in situ small-angle X-ray scattering, and transmission electron microscopy studies indicate that TFA coordinates the titanium center and forms a stable complex that is subsequently organized by the block copolymer species into ordered mesostructures. Solid-state NMR (19)F-->(1)H cross-polarization, (13)C{(1)H} two-dimensional heteronuclear correlation, and (1)H relaxation techniques were used to determine that PEO is predominantly incorporated within the TFA-modified titania, and that PPO environments encompass both microphase separated regions and interfacial regions composed of mixed PPO and TFA-modified titania. NMR (19)F multiple-quantum spin counting measurements suggest that -CF(3) groups of the trifluoroacetate ligands do not form clusters but instead randomly distribute within the inorganic component of the hybrid.
A New Heterocyclic Multicomponent Reaction For the Combinatorial Synthesis of Fused 3-Aminoimidazoles (1998)

When general and reliable, multicomponent reactions are among the most powerful tools in modern drug discovery. The principle of chemical ligation of reactive partners (see reaction scheme) has been employed to find a new, highly efficient synthesis of fused 3-aminoimidazoles.
Metabolism and disposition of 3-amino-1,5-dihydro-5-methyl-1-beta-D-ribofuranosyl-1,4,5,6, 8-pentaazaacenaphthylene in the rat. (1984)

Tricyclic nucleoside (TCN, NSC 154020) is a 7-deazapurine nucleoside possessing antitumor activity towards certain tumor cell lines in vitro. In vivo, TCN is readily interconvertible with its 5'-monophosphate ester. The present study demonstrates that TCN is metabolized by rat liver microsomes to a ring-opened bicyclic metabolite with loss of cytotoxicity toward Chinese hamster ovary cells in culture. Metabolism is mediated by hydrogen peroxide generated by the rat liver microsomes but is not dependent on cytochrome P-450. Isolated hepatocytes prepared from rat do not form detectable amounts of the ring-opened bicyclic metabolite. Unchanged TCN and the ring-opened bicyclic metabolite are excreted in the bile of rats with a cannulated bile duct, comprising 42 and 12% of an i.v. dose of TCN in 8 hr, respectively. The ring-opened bicyclic metabolite is not formed by red blood cells in vitro and could not be detected in blood in vivo. The fact that the ring-opened bicyclic metabolite appears in bile suggests that liver cells not present or not active in isolated hepatocyte preparations might produce the metabolite. Alternatively, the metabolite might be formed directly from TCN in bile, perhaps by hydrogen peroxide excreted into bile. In vivo, 56% of radiolabel was found in the upper and lower gastrointestinal tract and the feces 24 hr after an i.p. or i.v. dose of 100 mg of [5-methyl-14C]TCN/sq m. Urinary excretion of radiolabel was 21% of the dose of [14C]TCN in 24 hr. Biliary excretion of radiolabel was 65% of the dose of [14C]TCN in 8 hr. The fraction of radioactivity undergoing enterohepatic cycling with reabsorption from the gastrointestinal tract after excretion in bile is 84%.
A Kinetic and Thermodynamic Framework for the Hammerhead Ribozyme Reaction (1994)

A hammerhead ribozyme (HH16) with eight potential base pairs in each of the substrate recognition helices stabilized product binding sufficiently to enable investigation of the ligation of oligonucleotides bound to the ribozyme. All individual rate constants for product association and dissociation were determined. The following conclusions were obtained for HH16 from the analysis performed at 50 mM Tris, pH 7.5, 10 mM MgCl2, and 25 degrees C. (1) HH16 cleaves bound substrate with a rate constant of k2 = 1 min-1, similar to rate constants obtained with other hammerhead ribozymes. (2) k-2, the rate of ligation of the 5' product and 3' product to form substrate, equaled 0.008 min-1, indicating an approximately 100-fold preference for the formation of products on the ribozyme. This internal equilibrium, compared with that for the overall solution reaction, gives an effective concentration (EC) of 10(-2) M for the two products bound to the ribozyme. This low EC suggests that upon cleavage of S the hammerhead complex acquires a "floppiness" which provides an entropic advantage for the formation of products on the ribozyme. (3) Product and substrate association rate constants were in the range of 10(7)-10(8) M-1 min-1, comparable to values determined for short helices. (4) The stabilities of ribozyme/product complexes were similar to affinities predicted from helix-coil transitions of simple RNA duplexes, providing no indication of additional tertiary interactions. The products, P1 and P2, stabilize one another 4-fold on the ribozyme. (5) The dissociation constant for the binding of the substrate to the ribozyme was estimated to be about 10(-17) M. These results allowed the construction of a free energy profile for the reaction of HH16, and provide a basis for future mechanistic studies.
Growth of Keloid‐Producing Fibroblasts in Commercially Available Serum‐Free Media (1999)

The purpose of this study was to update our in vitro serum-free keloid fibroblast (KF) model by use of commercially available media. Prior evaluations of fibroblast characteristics in vitro, especially that of growth factor measurement, have been confounded by the presence of serum-containing media. KFs were obtained from patients undergoing facial keloid removal. The 4 commercially available serum-free media evaluated were AIM-V (Gibco, Grand Island, NY), Fibroblast Growth Medium (FGM; Clonetics, San Diego, CA), HB GRO (Irvine Scientific, Santa Ana, CA), and UltraCULTURE (BioWhittaker Inc, Walkersville, MD). The main outcome measures were sustained KF growth and viability as compared with serum-based models. The KFs in UltraCULTURE had a higher viability but did not grow as well as in FGM. The KFs in HB GRO and AIM-V demonstrated significantly decreased viability. Because of FGM's satisfactory proliferative support and viability comparable with serum-based medium, it is recommended for the in vitro propagation of keloid-producing fibroblasts.
Efficacy and long‐term patency of fenestrated amplatzer devices in children (2007)

Implantation of fenestrated atrial devices is feasible and effective; but the occlusion rate is high. Further research on fenestrated atrial septal devices with better long-term patency, and effective antithrombotic drug treatment is necessary.
Drug carrier systems for anticancer agents: A review (2008)

Poor aqueous solubility and adverse effects in cancer treatment using cytotoxicity or hormone therapy are frequently encountered during formulation and usage of conventional drugs. This paper reviews application of various solubilizers and carriers (polymers, cyclodextrins, dendrimers and proteins and amino acids) being used for improving therapeutic efficacy of these agents. Preparation of microspheres, microcapsules and nanospheres to improve aqueous solubility, and potential of liposomes and nanoparticles as effective drug delivery tools have been discussed.
A tumor suppressor locus within 3p14-p12 mediates rapid cell death of renal cell carcinoma in vivo. (1994)

High frequency loss of alleles and cytogenetic aberrations on the short arm of chromosome 3 have been documented in renal cell carcinoma (RCC). Potentially, three distinct regions on 3p could encode tumor suppressor genes involved in the genesis of this cancer. We report that the introduction of a centric fragment of 3p, encompassing 3p14-q11, into a highly malignant RCC cell line resulted in a dramatic suppression of tumor growth in athymic nude mice. Another defined deletion hybrid contained the region 3p12-q24 of the introduced human chromosome and failed to suppress tumorigenicity. These data functionally define a tumor suppressor locus, nonpapillary renal carcinoma-1 (NRC-1), within 3p14-p12, the most proximal region of high frequency allele loss in sporadic RCC as well as the region containing the translocation breakpoint in familial RCC. Furthermore, we provide functional evidence that NRC-1 controls the growth of RCC cells by inducing rapid cell death in vivo.
Depletion of Plasmacytoid Dendritic Cells Inhibits Tumor Growth and Prevents Bone Metastasis of Breast Cancer Cells (2012)

Elevated levels of plasmacytoid dendritic cells (pDC) have been reported in breast cancer patients, but the significance remains undefined. Using three immunocompetent mouse models of breast cancer bone metastasis, we identified a key role for pDC in facilitating tumor growth through immunosuppression and aggressive osteolysis. Following infiltration of macrophages upon breast cancer dissemination, there was a steady increase in pDC within the bone, which resulted in a sustained Th2 response along with elevated levels of regulatory T cells and myeloid-derived suppressor cells. Subsequently, pDC and CD4(+) T cells, producing osteolytic cytokines, increased with tumor burden, causing severe bone damage. Microcomputed tomography and histology analyses of bone showed destruction of femur and tibia. The therapeutic significance of this finding was confirmed by depletion of pDC, which resulted in decreased tumor burden and bone loss by activating tumor-specific cytolytic CD8(+) T cells and decreasing suppressor cell populations. Thus, pDC depletion may offer a novel adjuvant strategy to therapeutically influence breast cancer bone metastasis.