gebhart/patrepeval huggingface dataset:
Molecular characterization of H9N2 influenza viruses: Were they the donors of the “internal” genes of H5N1 viruses in Hong Kong? (1999)

The origin of the H5N1 influenza viruses that killed six of eighteen infected humans in 1997 and were highly pathogenic in chickens has not been resolved. These H5N1 viruses transmitted directly to humans from infected poultry. In the poultry markets in Hong Kong, both H5N1 and H9N2 influenza viruses were cocirculating, raising the possibility of genetic reassortment. Here we analyze the antigenic and genetic features of H9N2 influenza viruses with different epidemiological backgrounds. The results suggest that the H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages. Among the chicken H9N2 viruses, six of the gene segments were apparently derived from an earlier chicken H9N2 virus isolated in China, whereas the PB1 and PB2 genes are closely related to those of the H5N1 viruses and a quail H9N2 virus-A/quail/Hong Kong/G1/97 (Qa/HK/G1/97)-suggesting that many of the 1997 chicken H9 isolates in the markets were reassortants. The similarity of the internal genes of Qa/HK/G1/97 virus to those of the H5N1 influenza viruses suggests that the quail virus may have been the internal gene donor. Our findings indicate that the human and poultry H5N1 influenza viruses in Hong Kong in 1997 were reassortants that obtained internal gene segments from Qa/HK/G1/97. However, we cannot be certain whether the replicate complex of H5N1 originated from Qa/HK/G1/97 or whether the reverse transfer occurred; the available evidence supports the former proposal.
Prediction of HIV Peptide Epitopes by a Novel Algorithm (1996)

Identification of promiscuous or multideterminant T cell epitopes is essential for HIV vaccine development, however, current methods for T cell epitope identification are both cost intensive and labor intensive. We have developed a computer-driven algorithm, named EpiMer, which searches protein amino acid sequences for putative MHC class I- and/or class II-restricted T cell epitopes. This algorithm identifies peptides that contain multiple MHC-binding motifs from protein sequences. To evaluate the predictive power of EpiMer, the amino acid sequences of the HIV-1 proteins nef, gp160, gag p55, and tat were searched for regions of MHC-binding motif clustering. We assessed the algorithm's predictive power by comparing the EpiMer-predicted peptide epitopes to T cell epitopes that have been published in the literature. The EpiMer method of T cell epitope identification was compared to the standard method of synthesizing short, overlapping peptides and testing them for immunogenicity (overlapping peptide method), and to an alternate algorithm that has been used to identify putative T cell epitopes from primary structure (AMPHI). For the four HIV-1 proteins analyzed, the in vitro testing of EpiMer peptides for immunogenicity would have required the synthesis of fewer total peptides than either AMPHI or the overlapping peptide method. The EpiMer algorithm proved to be more efficient and more sensitive per amino acid than both the overlapping peptide method and AMPHI. The EpiMer predictions for these four HIV proteins are described. Since EpiMer-predicted peptides have the potential to bind to multiple MHC alleles, they are strong candidates for inclusion in a synthetic HIV vaccine.
Development of an adenovirus vector with tetracycline-regulatable human tumor necrosis factor alpha gene expression. (1997)

Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine with direct antitumor activity. However, clinical trials using TNF-alpha for cancer treatment have been disappointing due in part to its severe side effects, and it has been estimated that TNF-alpha therapy would be effective only at 5-25 times the maximum tolerated dose. We have recently modified a tetracycline (Tc) repressor/operator-based mammalian gene expression system and have generated a Tc-responsive recombinant adenovirus vector, AdVtTA.TNF-alpha. A variety of human tumor cells and T lymphocytes transduced by AdVtTA.TNF-alpha secreted high-titer (5,000-100,000 pg/10(6) cells/24 h) and biologically active TNF-alpha in the absence of Tc. Expression of TNF-alpha in the transduced cells was nondetectable when the culture medium contained as little as 0.1 microg/ml of Tc. At least a fraction of the clonogenic cells from human peripheral blood stem cell concentrates were also transducible by AdVtTA.TNF-alpha. The availability of this type of adenovirus vector opens a door to tumor- or organ-specific delivery of high-dose TNF-alpha and other therapeutic gene products for systemic cancer gene therapy.
Mechanisms of p34cdc2 regulation. (1993)

The kinase activity of human p34cdc2 is negatively regulated by phosphorylation at Thr-14 and Tyr-15. These residues lie within the putative nucleotide binding domain of p34cdc2. It has been proposed that phosphorylation within this motif ablates the binding of ATP to the active site of p34cdc2, thereby inhibiting p34cdc2 kinase activity (K. Gould and P. Nurse, Nature [London] 342:39-44, 1989). To understand the mechanism of this inactivation, various forms of p34cdc2 were tested for the ability to bind nucleotide. The active site of p34cdc2 was specifically modified by the MgATP analog 5'-p-fluorosulfonylbenzoyladenosine (FSBA). The apparent Km for modification of wild-type, monomeric p34cdc2 was 148 microM FSBA and was not significantly affected by association with cyclin B. Tyrosine-phosphorylated p34cdc2 was modified by FSBA with a slightly higher Km (241 microM FSBA). FSBA modification of both tyrosine-phosphorylated and unphosphorylated p34cdc2 was competitively inhibited by ATP, and half-maximal inhibition in each case occurred at approximately 250 microM ATP. In addition to being negatively regulated by phosphorylation, the kinase activity of p34cdc2 was positively regulated by the cyclin-dependent phosphorylation of Thr-161. Mutation of p34cdc2 at Thr-161 resulted in the formation of an enzymatically inactive p34cdc2/cyclin B complex both in vivo and in vitro. However, mutation of Thr-161 did not significantly affect the ability of p34cdc2 to bind nucleotide (FSBA). Taken together, these results indicate that inhibition of p34cdc2 kinase activity by phosphorylation of Tyr-15 (within the putative ATP binding domain) or by mutation of Thr-161 involves a mechanism other than inhibition of nucleotide binding. We propose instead that the defect resides at the level of catalysis.
The search for a potent DNA vaccine against AIDS: the enhancement of immunogenicity by chemical and genetic adjuvants. (1999)

DNA vaccination is a new way to generate antigen specific immune responses by inoculating plasmid DNA encoding microbial genes. We believe that the use of immunologic adjuvants together with DNA vaccines is a promising way to enhance and optimize DNA-derived immunity. Various chemical and genetic adjuvants have been explored in our recent study. Data from these studies suggests that adjuvants exert their immunomodulatory properties through several mechanisms such as lymphoid cells recruitment, cytokine induction, and the facilitation of DNA entry into cells. Furthermore, each adjuvant has unique immunomodulatory effects on cell-mediated and humoral immune responses induced by DNA vaccination to human immunodeficiency virus type 1. To optimize the desirable immune response, the choice of adjuvant and decision of immunization route are important considerations. A similar approach may be useful potentiating anticancer immunotherapy as well.
Identification and Characterization of a Bile Acid 7α-Dehydroxylation Operon in Clostridium sp. Strain TO-931, a Highly Active 7α-Dehydroxylating Strain Isolated from Human Feces (2000)

Clostridium sp. strain TO-931 can rapidly convert the primary bile acid cholic acid to a potentially toxic compound, deoxycholic acid. Mixed oligonucleotide probes were used to isolate a gene fragment encoding a putative bile acid transporter from Clostridium sp. strain TO-931. This DNA fragment had 60% nucleotide sequence identity to a known bile acid transporter gene from Eubacterium sp. strain VPI 12708, another bile acid-7alpha-dehydroxylating intestinal bacterium. The DNA (9.15 kb) surrounding the transporter gene was cloned from Clostridium sp. strain TO-931 and sequenced. Within this larger DNA fragment was a 7.9-kb region, containing six successive open reading frames (ORFs), that was encoded by a single 8.1-kb transcript, as determined by Northern blot analysis. The gene arrangement and DNA sequence of the Clostridium sp. strain TO-931 operon are similar to those of a Eubacterium sp. strain VPI 12708 bile acid-inducible operon containing nine ORFs. Several genes in the Eubacterium sp. strain VPI 12708 operon have been shown to encode products required for bile acid 7alpha-dehydroxylation. In Clostridium sp. strain TO-931, genes potentially encoding bile acid-coenzyme A (CoA) ligase, 3alpha-hydroxysteroid dehydrogenase, bile acid 7alpha-dehydratase, bile acid-CoA hydrolase, and a bile acid transporter were similar in size and exhibited amino acid homology to similar gene products from Eubacterium sp. strain VPI 12708 (encoded by baiB, baiA, baiE, baiF, and baiG, respectively). However, no genes similar to Eubacterium sp. strain VPI 12708 biaH or baiI were found in the Clostridium sp. strain TO-931 bai operon, and the two putative Eubacterium sp. strain VPI 12708 genes, baiC and baiD, were arranged in one continuous ORF in Clostridium sp. strain TO-931. Intergene regions showed no significant DNA sequence similarity, but primer extension analysis identified a region 115 bp upstream from the first ORF that exhibited 58% identity to a bai operator/promoter region identified in Eubacterium sp. strain VPI 12708. These results indicate that the gene organization, gene product amino acid sequences, and promoters of the bile acid-inducible operons of Clostridium sp. strain TO-931 and Eubacterium sp. strain VPI 12708 are highly conserved.
Lipid Rafts Exist as Stable Cholesterol-independent Microdomains in the Brush Border Membrane of Enterocytes (2001)

Glycosphingolipid/cholesterol-rich membranes ("rafts")can be isolated from many types of cells, but their existence as stable microdomains in the cell membrane has been elusive. Addressing this problem, we studied the distribution of galectin-4, a raft marker, and lactase, a protein excluded from rafts, on microvillar vesicles from the enterocyte brush border membrane. Magnetic beads coated with either anti-galectin-4 or anti-lactase antibodies were used for immunoisolation of vesicles followed by double immunogold labeling of the two proteins. A morphometric analysis revealed subpopulations of raft-rich and raft-poor vesicles by the following criteria: 1) the lactase/galectin-4 labeling ratio/vesicle captured by the anti-lactase beads was significantly higher (p < or = 0.01) than that of vesicles captured by anti-galectin-4 beads, 2) subpopulations of vesicles labeled by only one of the two antibodies were preferentially captured by beads coated with the respective antibody (p < or = 0.01), 3) the average diameter of "galectin-4 positive only" vesicles was smaller than that of vesicles labeled for lactase. Surprisingly, pretreatment with methyl-beta-cyclodextrin, which removed >70% of microvillar cholesterol, did not affect the microdomain localization of galectin-4. We conclude that stable, cholesterol-independent raft microdomains exist in the enterocyte brush border.
Singlet molecular oxygen and superoxide dismutase (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSinglet molecular oxygen and superoxide dismutaseA. Paul Schaap, Arthur L. Thayer, Gary R. Faler, Kiyoshi Goda, and Tokuji KimuraCite this: J. Am. Chem. Soc. 1974, 96, 12, 4025–4026Publication Date (Print):June 1, 1974Publication History Published online1 May 2002Published inissue 1 June 1974https://pubs.acs.org/doi/10.1021/ja00819a055https://doi.org/10.1021/ja00819a055research-articleACS PublicationsRequest reuse permissionsArticle Views300Altmetric-Citations64LEARN 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
A self-administered hand symptom diagram for the diagnosis and epidemiologic study of carpal tunnel syndrome. (1990)

Noninvasive tests for carpal tunnel syndrome (CTS) are of limited diagnostic value. A self-administered hand symptom diagram has been developed for use in the diagnosis and epidemiologic study of CTS. Diagrams are rated classic CTS, probable, possible or unlikely. Diagram ratings were compared with nerve conduction diagnoses in 110 patients with upper extremity complaints. A hand diagram rating of classic or probable CTS had sensitivity of 0.64, specificity of 0.73 and positive predictive value of 0.58. The negative predictive value of an unlikely diagram was 0.91. We conclude that the diagram is a useful diagnostic tool and may be valuable for occupational and population screening.
Reconstitution of the Bacterial Core Light-harvesting Complexes of Rhodobacter sphaeroides and Rhodospirillum rubrum with Isolated α- and β-Polypeptides, Bacteriochlorophyll a, and Carotenoid (1995)

Methodology has been developed to reconstitute carotenoids and bacteriochlorophyll alpha with isolated light-harvesting complex I (LHI) polypeptides of both Rhodobacter sphaeroides and Rhodospirillum rubrum. Reconstitution techniques first developed in this laboratory using the LHI polypeptides of R. rubrum, R. sphaeroides, and Rhodobacter capsulatus reproduced bacteriochlorophyll alpha spectral properties characteristic of LHI complexes lacking carotenoids. In this study, carotenoids are supplied either as organic-solvent extracts of chromatophores or as thin-layer chromatography or high performance liquid chromatography-purified species. The resulting LHI complexes exhibit carotenoid and bacteriochlorophyll a spectral properties characteristic of native LHI complexes of carotenoid-containing bacteria. Absorption and circular dichroism spectra support the attainment of a native-like carotenoid environment in the reconstituted LHI complexes. For both R. sphaeroides- and R. rubrum-reconstituted systems, fluorescence excitation spectra reveal appropriate carotenoid to bacteriochlorophyll alpha energy-transfer efficiencies based on comparisons with the in vivo systems. In the case of R. rubrum reconstitutions, carotenoids afford protection from photodynamic degradation. Thus, carotenoids reconstituted into LHI exhibit spectral and functional characteristics associated with native pigments. Heterologous reconstitutions demonstrate the applicability of the developed assay in dissecting the molecular environment of carotenoids in light-harvesting complexes.
New Preparation of Aminoboronic Acids (1988)

Abstract A new preparation of aminoboronic acids, starting from N-trimethylsilyl derivatives of olefinic amines and utilizing the hydroboration reaction, is described as a “one pot” reaction.
Breakeven criteria for the GaInNAs junction in GaInP/GaAs/GaInNAs/Ge four‐junction solar cells (2002)

Abstract The four‐junction GaInP/GaAs/GaInNAs/Ge solar cell structure holds the promise of efficiencies exceeding those of the GaInP/GaAs/Ge three‐junction cell, which at present is the benchmark for high‐efficiency multijunction cell performance. The performance of GaInNAs junctions demonstrated to date has been insufficient for the realization of these projected efficiency gains, owing to poor minority‐carrier properties in the GaInNAs. However, incremental improvements in the GaInNAs junctions have brought this breakeven point within sight. In this paper, we use a semiempirical approach to estimate the efficiency of the GaInP/GaAs/GaInNAs/Ge four‐junction solar cell structure as a function of the performance parameters of the GaInNAs third junction. The results provide guidance on the extent to which the current and voltage of present‐day GaInNAs junctions will need to be improved in order for the resulting four‐junction cell to realize its potential for efficiencies higher than that of GaInP/GaAs/Ge benchmark. Published in 2002 by John Wiley &amp; Sons, Ltd.
Decreased Mutation Rate for Cellular Resistance to Doxorubicin and Suppression of mdrl Gene Activation by the Cyclosporin PSC 833 (1995)

Our results suggest that treatment with multidrug resistance modulators such as PSC 833 together with multidrug resistance-related cytotoxins may suppress the activation of mdr1 and prevent the emergence of resistant cancer cell clones with the multidrug-resistant phenotype.
Ein neuer Zugang zu 2′‐O‐Alkylribonucleosiden und Eigenschaften deren Oligonucleotide (1995)

A New Access to 2′‐ O ‐Alkylated Ribonucleosides and Properties of 2′‐ O ‐Alkylated Oligoribonucleotides A general access to 2′‐ O ‐alkylated ribonucleosides using the key intermediate 5 is presented. The incorporation of 2′‐ O ‐‘ethyleneglycol’‐ and 2′‐ O ‐‘glycerol’‐substituted ( i.e. , 2′‐ O ‐(2‐hydroxyethyl)‐ and 2′‐ O ‐(2,3‐dihydroxypropyl)‐substituted) ribonucleosides into oligonucleotides affords a new generation of oligonucleotides with high affinity for RNA, high specificity, and increased nuclease resistance.
Nanopore Analysis of β-Amyloid Peptide Aggregation Transition Induced by Small Molecules (2011)

β-Amyloid 42 (Aβ42) is the predominant form of the amyloid peptide, which is found in the plaques of the brains of Alzheimer's (AD) patients and is one of the most abundant components in amyloid aggregates. Information of the Aβ42 aggregation states is essential for developing an understanding of the pathologic process of amyloidoses. Here, we used α-hemolysin (α-HL) pores to probe the different aggregation transition of Aβ42 in the presence of β-cyclodextrin (β-CD), a promoter of Aβ42 aggregations, and in the presence of Congo red (CR), an inhibitor of aggregations. Analyzing the characteristic transit duration times and blockade currents showed that β-CD and CR have opposite effects on the aggregation of Aβ42. Translocation events of the monomeric Aβ42 peptide were significantly lower in amplitude currents than protofilaments, and protofilaments were captured in the α-HL nanopore with a longer duration time. CR binds to Aβ42 and its peptide fibrils by reducing the aggregated fibrils formation. In this process it is assumed CR interferes with intermolecular hydrogen bonding present in the aggregates. In contrast to CR, β-CD promotes the aggregation of Aβ42. These differences can readily be analyzed by monitoring the corresponding characteristic blockade events using a biological α-HL nanopore.
Spontaneous Priming of a Downstream Module in 6-Deoxyerythronolide B Synthase Leads to Polyketide Biosynthesis (1998)

Modular polyketide synthases such as 6-deoxyerythronolide B synthase (DEBS) catalyze the biosynthesis of structurally complex natural products by repetitive condensation of simple carboxylic acid monomers. The synthase can be divided into groups of domains, called "modules", each of which is responsible for one cycle of chain extension and processing. The modular nature of these enzymes suggests that the biosynthetic pathway might be rationally reprogrammed by manipulation of synthases at the domain level. Although, several examples of successful engineering of DEBS have been reported, a critical issue which has not been well-studied is the tolerance of "downstream" active sites to nonnatural substrates. Here, we report that the terminal modules of DEBS, which normally process highly functionalized intermediates, are competent to carry out their natural functions on smaller, more simple substrates. Expressed in the absence of other DEBS proteins, the DEBS3 protein, which normally carries out the final two extension cycles in the synthesis of 6-deoxyerythronolide B (6-dEB), is spontaneously primed with a C3 carboxylic acid. This substrate is then extended through two condensation cycles to form a triketide. Tolerance of the "shortened" intermediates in the biosynthesis of this triketide, in combination with results reported elsewhere [Jacobsen, J. R., Hutchinson, C. R., Cane, D. E., and Khosla, C. (1997) Science 277, 367-369], suggests that relaxed substrate specificity may be a common feature of modular polyketide synthases. Interestingly, priming of DEBS3 appears to proceed, not by acyltransfer from propionyl-CoA, but by decarboxylation of an enzyme-bound methylmalonyl extender unit. This is the second example of decarboxylative priming within DEBS [see also Pieper, R., Gokhale, R. S., Luo, G., Cane, D. E., and Khosla, C. (1997) Biochemistry 36, 1846-1851] and suggests that, in the absence of an acceptable primer (or transferred intermediate), decarboxylative priming of ketosynthase domains may be a general property of modular polyketide synthases.
Human erythropoietin gene expression in transgenic mice: multiple transcription initiation sites and cis-acting regulatory elements. (1990)

Erythropoietin (EPO) is the primary humoral regulator of mammalian erythropoiesis. The single-copy EPO gene is normally expressed in liver and kidney, and increased transcription is induced by anemia or cobalt chloride administration. To identify cis-acting DNA sequences responsible for regulated expression, transgenic mice were generated by microinjection of a 4-kilobase-pair (kb) (tgEPO4) or 10-kb (tgEPO10) cloned DNA fragment containing the human EPO gene, 0.7 kb of 3'-flanking sequence, and either 0.4 or 6 kb of 5'-flanking sequence, respectively. tgEPO4 mice expressed the transgene in liver, where expression was inducible by anemia or cobalt chloride, kidney, where expression was not inducible, and other tissues that do not normally express EPO. Human EPO RNA in tgEPO10 mice was detected only in liver of anemic or cobalt-treated mice. Both tgEPO4 and tgEPO10 mice were polycythemic, demonstrating that the human EPO RNA transcribed in liver is functional. These results suggest that (i) a liver inducibility element maps within 4 kb encompassing the gene, 0.4 kb of 5'-flanking sequence, and 0.7 kb of 3'-flanking sequence; (ii) a negative regulatory element is located between 0.4 and 6 kb 5' to the gene; and (iii) sequences required for inducible kidney expression are located greater than 6 kb 5' or 0.7 kb 3' to the gene. RNase protection analysis revealed that human EPO RNA in anemic transgenic mouse liver and hypoxic human hepatoma cells is initiated from several sites, only a subset of which is utilized in nonanemic transgenic liver and human fetal liver.