gebhart/patrepeval huggingface dataset:
Succession of methanogenic archaea in rice straw incorporated into a Japanese rice field: estimation by PCR‐DGGE and sequence analyses (2005)

The succession and phylogenetic profiles of methanogenic archaeal communities associated with rice straw decomposition in rice-field soil were studied by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis followed by 16S rDNA sequencing. Nylon bags containing either leaf sheaths or blades were buried in the plowed layer of a Japanese rice field under drained conditions during the off-crop season and under flooded conditions after transplanting. In addition, rice straw samples that had been buried in the rice field under drained conditions during the off-crop season were temporarily removed during spring plowing and then re-buried in the same rice field under flooded conditions at transplanting. Populations of methanogenic archaea were examined by amplification of the 16S rRNA genes in the DNA extracted from the rice straw samples. No PCR product was produced for samples of leaf sheath or blade prior to burial or after burial under drained conditions, indicating that the methanogen population was very small during decomposition of rice straw under oxic conditions. Many common bands were observed in rice straw samples of leaf sheath and blade during decomposition of rice straw under flooded conditions. Cluster analysis based on DGGE patterns divided methanogenic archaeal communities into two groups before and after the mid-season drainage. Sequence analysis of DGGE bands that were commonly present were closely related to Methanomicrobiales and Rice cluster I. Methanomicrobiales, Rice cluster I and Methanosarcinales were major members before the mid-season drainage, whereas the DGGE bands that characterized methanogenic archaeal communities after the mid-season drainage were closely related to Methanomicrobiales. These results indicate that mid-season drainage affected the methanogenic archaeal communities irrespective of their location on rice straw (sheath and blade) and the previous history of decomposition during the off-crop season.
Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development (1997)

We have isolated and sequenced a novel 11-kDa virucidal protein, named cyanovirin-N (CV-N), from cultures of the cyanobacterium (blue-green alga) Nostoc ellipsosporum. We also have produced CV-N recombinantly by expression of a corresponding DNA sequence in Escherichia coli. Low nanomolar concentrations of either natural or recombinant CV-N irreversibly inactivate diverse laboratory strains and primary isolates of human immunodeficiency virus (HIV) type 1 as well as strains of HIV type 2 and simian immunodeficiency virus. In addition, CV-N aborts cell-to-cell fusion and transmission of HIV-1 infection. Continuous, 2-day exposures of uninfected CEM-SS cells or peripheral blood lymphocytes to high concentrations (e.g., 9,000 nM) of CV-N were not lethal to these representative host cell types. The antiviral activity of CV-N is due, at least in part, to unique, high-affinity interactions of CV-N with the viral surface envelope glycoprotein gp120. The biological activity of CV-N is highly resistant to physicochemical denaturation, further enhancing its potential as an anti-HIV microbicide.
Pharmacokinetic and ADME study of nanoparticle albumin-bound 17AAG (nab-17AAG) in mice (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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Background: Nab technology enhances tumor penetration of insoluble drugs by a novel mechanism of albumin receptor-mediated (gp60) endothelial trancytosis and improves drug accumulation in tumors via albumin-mediated binding to SPARC. The Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17AAG), is a better tolerated anti-cancer agent than its natural-product predecessor, geldanamycin. Rodent IV administration of nab-17AAG was performed to investigate: (i) the pharmacokinetic (PK) properties of 17AAG and its major metabolite, 17-amino geldanamycin (17AG) and, (ii) the absorption, distribution, metabolism, and excretion (ADME) profile of nab-17AAG. Methods: For PK evaluation, bolus tail-vein injections of nab-17AAG were administered in CD1 mice, at dose levels of 50, 100, and, 150 mg/kg. Blood samples (up to 0.6 mL) for PK analysis were obtained at the following target times: predose and at 0.0167, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 4, 8, 24, 36 and 48 hrs postdose. Mouse sera were analyzed for 17AAG and 17AG using a LC/MS analytical method. Noncompartmental PK parameters were estimated using WinNonlin software. For ADME studies, ICR mice received a single IV administration of nab-3H-17AAG at 150 mg/kg. Urine and fecal specimens were collected across 5 days at 4, 12, or 24 hr postdose intervals for analysis of nab-3H-17AAG-derived radioactivity. Results: Tmax for the parent, 17AAG, occurred at the first blood collection at all 3 dose levels, without dose-dependent trends. The max serum concentration of 17AAG increased with increasing dose but at a less than dose-proportional ratio for the different dose levels. Systemic exposure to 17AAG increased with increasing dosage and was dose proportional at the mid and high doses. Terminal elimination half-lives (HL) were similar for 17AAG & 17AG, ranging from 0.357 to 0.652 hrs with no consistent dose-dependent trends. Vz and Vss values for 17AAG were variable, but slightly greater in the high-dose group. Metabolic conversion of 17AAG to 17AG reached max concentration within 1 hr postdose and was greater at the higher dose levels. 17AG had a slightly longer HL (30 to 60 mins), a later Tmax (30 to 60 mins), a 3-fold lower exposure, and at least a 10-fold lower Cmax than 17AAG. ADME studies showed that nab-3H-17AAG was primarily excreted in feces (≥ 64%) and urine (≥ 17%) with no preferential tissue site for accumulation. Of three 3H-17AAG urine metabolites detected, less than 6% were related to17AAG. Conclusions: Application of nab technology to 17AAG resulted in a formulation of 17AAG with the expected characteristics of albumin-bound nanoparticles, inclusive of a linear PK profile with respect to dose and large volume of distribution. ADME studies showed that nab-3H-17AAG was primarily excreted in feces and urine with no preferential site for tissue accumulation.
Distinct Recognition Modes of FXXLF and LXXLL Motifs by the Androgen Receptor (2004)

Among nuclear receptors, the androgen receptor (AR) is unique in that its ligand-binding domain (LBD) interacts with the FXXLF motif in the N-terminal domain, resembling coactivator LXXLL motifs. We compared AR- and estrogen receptor alpha-LBD interactions of the wild-type AR FXXLF motif and coactivator transcriptional intermediary factor 2 LXXLL motifs and variants of these motifs. Random mutagenesis revealed a key role for the F residues in FXXLF motifs in high-affinity and selective AR LBD interaction. The FXXLF motif in full-length AR and transcriptional intermediary factor 2 LXXLL motifs competed for an overlapping binding site. A computer model of the AR LBD/AR FXXLF complex showed that the bulky F residues are buried in a deep coactivator-binding groove. The corresponding groove in estrogen receptor alpha LBD is considerably shallower, explaining lack of binding of any of the FXXLF motifs tested. FXXLF and LXXLL motif interaction depended on different charged amino acid residues in the AR LBD present at opposite ends of the coactivator groove. In conclusion, our data demonstrate the importance of a deep hydrophobic groove and alternative usage of charged amino acids in specifying peptide binding to the AR LBD.
Hydrogen bonding of sulfur ligands in blue copper and iron-sulfur proteins: detection by resonance Raman spectroscopy (1987)

The resonance Raman spectrum of the blue copper protein azurin from Alcaligenes denitrificans exhibits nine vibrational modes between 330 and 460 cm-1, seven of which shift 0.4-3.0 cm-1 to lower energy after incubation of the protein in D2O. These deuterium-dependent shifts have been previously ascribed to exchangeable protons on imidazole ligands [Nestor, L., Larrabee, J. A., Woolery, G., Reinhammar, B., & Spiro, T. G. (1984) Biochemistry 23, 1084] or to exchangeable protons on amide groups which are hydrogen bonded to the cysteine thiolate ligands (a feature common to all blue copper proteins of known structure). In order to distinguish between these two possibilities, a systematic investigation of Fe2S2(Cys)4-containing proteins was undertaken. Extensive hydrogen bonding between sulfur ligands and the polypeptide backbone had been observed in the crystal structure of ferredoxin from Spirulina platensis. The resonance Raman spectrum of this protein is typical of a chloroplast-type ferredoxin and exhibits deuterium-dependent shifts of -0.3 to -0.5 cm-1 in the Fe-S modes at 283, 367, and 394 cm-1 (assigned to the bridging sulfurs) and -0.6 to -0.8 cm-1 in the Fe-S modes at 328 and 341 cm-1 (assigned to the terminal cysteine thiolates). Considerably greater deuterium sensitivity is observed in the Raman spectra of spinach ferredoxin and bovine adrenodoxin, particularly for the symmetric stretching vibration of the Fe2S2 moiety at approximately 390 cm-1. This feature decreases by 0.8 and 1.1 cm-1, respectively, for the two oxidized proteins in D2O and by 1.8 cm-1 for reduced adrenodoxin in D2O.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular Pathogenesis ofSalmonella entericaSerotype Typhimurium-Induced Diarrhea (2002)

Recent studies on the molecular pathogenesis of Salmonella enterica serotype Typhimurium-induced enterocolitis using tissue culture models and the neonatal calf model have led to an improved understanding of key events occurring during the complex series of host-pathogen interactions leading to diarrhea.In vitro studies show that Salmonella serovar Typhimurium translocates a number of type III secreted effector proteins, including SipA, SopA, SopB, SopD, and SopE2 into host cells.SipA, SopA, SopB, SopD, and SopE2 are required for eliciting infiltration of neutrophils in the calf model of enterocolitis, presumably by inducing the production of chemoattractant chemokines in bovine ileal tissue during Salmonella serovar Typhimurium infection.The resulting acute inflammatory response is associated with an increase in vascular permeability resulting in mucosal edema.Furthermore, the influx of neutrophils is associated with necrosis of the uppermost ileal mucosa.The injury to the intestinal epithelium leads to leakage of extravascular fluids and massive transmigration of neutrophils into the intestinal lumen, a process normally prevented by the epithelial permeability barrier.These data suggest that the severe fluid loss observed during Salmonella serovar Typhimurium-induced enterocolitis is at least in part due to an inflammatory mechanism which causes liquid to flow from the blood to the intestinal lumen.
Cancer-associated mutations at the INK4a locus cancel cell cycle arrest by p16 INK4a but not by the alternative reading frame protein p19 ARF (1997)

The INK4a gene, one of the most frequently disrupted tumor suppressor loci in human cancer, encodes two unrelated proteins, p16INK4a and p19ARF, each of which is capable of inducing cell cycle arrest. Splicing of alternative first exons (1 alpha vs. 1 beta) to a common second exon within INK4a generates mRNAs in which exon 2 sequences are translated in two different reading frames. One of the products, the cyclin D-dependent kinase inhibitor p16INK4a, is functionally inactivated by mutations or deletions in a wide variety of cancers. However, because many such mutations reside in exon 2, they also affect the alternative reading frame (ARF) protein. To determine whether such mutations disrupt p19ARF function, we introduced naturally occurring missense mutations into mouse INK4a exon 2 sequences and tested mutant p16INK4a and p19ARF proteins for their ability to inhibit cell cycle progression. Six p19ARF point mutants remained fully active in mediating cell cycle arrest in NIH 3T3 fibroblasts, whereas two of the corresponding mutations within p16INK4a resulted in complete loss of activity. Analysis of p19ARF deletion mutants indicated that the unique aminoterminal domain encoded by exon 1 beta was both necessary and sufficient for inducing G1 arrest. Therefore, cancer-associated mutations within exon 2 of the INK4a gene specifically target p16INK4a, and not p19ARF, for inactivation.
Increase in Tear Film Lipid Layer Thickness Following Treatment with Warm Compresses in Patients with Meibomian Gland Dysfunction (2003)

Warm, moist compress therapy applied to the skin of the closed eyelids increases TFLLT for subjects with MGD by more than 80%, 5 minutes after initiating treatment and an additional 20% after 15 minutes of treatment. This study supports clinical experience and previous reports on warm, moist compress therapy as an effective treatment for meibomian gland dysfunction.
Analysis of the plasma elimination kinetics and conformational stabilities of native, proteinase-complexed and reactive site cleaved serpins: comparison of .alpha.1-proteinase inhibitor, .alpha.1-antichymotrypsin, antithrombin III, .alpha.2-antiplasmin, angiotensinogen, and ovalbumin (1991)

Proteinase inhibitors of the serpin superfamily may exist in one of three distinct conformations: the native form, a fully active protein with the reactive site loop intact; the proteolytically modified form in which inhibitory capacity is abolished; and the proteinase-complexed form, a stable equimolar complex between the inhibitor and a target proteinase. Here, the specificity and kinetics of the plasma elimination of different serpin conformations are compared. Proteinase-complexed serpins were rapidly cleared from the circulation. However, the native and modified forms were not cleared rapidly, indicating that the receptor-mediated pathways which recognize the complexes fail to recognize the native and modified forms. This result suggests that significant structural differences exist between modified and proteinase-complexed serpins. The structural differences were probed by using transverse urea gradient gel electrophoresis, a technique that allows comparisons of the conformational stabilities of proteins. With the exception of the noninhibitory serpins ovalbumin and angiotensinogen, the modified and proteinase-complexed serpins were both stabilized thermodynamically compared to the native forms. In addition, the proteinase component of the serpin-proteinase complex was usually thermodynamically stabilized. These data are used to compare the conformations of serpin-proteinase complexes with those of native and modified serpins; they are discussed in terms of a model whereby serpins inhibit proteinases in a manner similar to that described for other types of protein inhibitors of serine proteinases.
Plasma Epstein-Barr Virus DNA and Residual Disease After Radiotherapy for Undifferentiated Nasopharyngeal Carcinoma (2002)

Levels of post-treatment plasma EBV DNA in patients with NPC appear to strongly predict progression-free and overall survival and to accurately reflect the post-treatment residual tumor load.
Vitamin K-Dependent Formation of γ-Carboxyglutamic Acid (1977)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Propagation of human parvovirus B19 in primary culture of erythroid lineage cells derived from fetal liver (1989)

Erythroid lineage cells derived from fetal liver were demonstrated to be target cells for human parvovirus B19 infection. B19 virus antigen-positive serum was inoculated into primary cultures containing erythroid lineage cells enriched from fetal liver. The B19 virus antigen was detected on about 5% of cells in the culture by immunofluorescence staining, and the stained cells were identified as erythroid lineage cells by double staining with anti-B19 virus-positive serum and anti-erythroid lineage monoclonal antibody. The immunofluorescence staining study also revealed that the B19 virus antigen localized in the nucleus and the periphery of cytoplasm. We also detected B19 virus DNA, which was generated by replication in the infected cells, not only in the cells but also in the culture supernatants, in which the amount of B19 DNA increased depending on the period of culture, indicating that the cells infected with B19 virus produced B19 virus and released it into the medium. The ability of B19 virus released into the medium to infect fetal erythroid lineage cells was demonstrated quantitatively. Because of the absence of any cytopathic effect of B19 virus during culture periods of at least 15 days, this culture system should be useful in the study of B19 virus replication and in vitro generation of B19 virus. In addition, the present study may contribute to a better understanding of the pathogenesis of hydrops fetalis, which is probably associated with B19 virus infection during pregnancy.
Development of a compact proton scanning system in Uppsala with a moveable second magnet (2000)

A scanned proton beam yields dose distributions that in most cases are superior to passively scattered proton beams and to other external radiation treatment modalities. The present paper gives a description of the scanning system that has been developed at the Svedberg Laboratory (TSL) in Uppsala. The scanning technique and the technical design are described. The solution with a small pole gap of the magnets and a moveable second magnet results in a very compact scanning head, which can therefore be incorporated in a gantry of relatively limited size. A prototype was constructed that has been used to realize various dose distributions with a scanned beam of 180 MeV protons at TSL.
A Methylated Phosphate Group and Four Amide-linked Acyl Chains in Leptospira interrogans Lipid A (2004)

Leptospira interrogans differs from other spirochetes in that it contains homologs of all the Escherichia coli lpx genes required for the biosynthesis of the lipid A anchor of lipopolysaccharide (LPS). LPS from L. interrogans cells is unusual in that it activates TLR2 rather than TLR4. The structure of L. interrogans lipid A has now been determined by a combination of matrix-assisted laser desorption ionization time-of-flight mass spectrometry, NMR spectroscopy, and biochemical studies. Lipid A was released from LPS of L. interrogans serovar Pomona by 100 degrees C hydrolysis at pH 4.5 in the presence of SDS. Following purification by anion exchange and thin layer chromatography, the major component was shown to have a molecular weight of 1727. Mild hydrolysis with dilute NaOH reduced this to 1338, consistent with the presence of four N-linked and two O-linked acyl chains. The lipid A molecules of both the virulent and nonvirulent forms of L. interrogans serovar Icterohaemorrhagiae (strain Verdun) were identical to those of L. interrogans Pomona by the above criteria. Given the selectivity of L. interrogans LpxA for 3-hydroxylaurate, we propose that L. interrogans lipid A is acylated with R-3-hydroxylaurate at positions 3 and 3' and with R-3-hydroxypalmitate at positions 2 and 2'. The hydroxyacyl chain composition was validated by gas chromatography and mass spectrometry of fatty acid methyl esters. Intact hexa-acylated lipid A of L. interrogans Pomona was also analyzed by NMR, confirming the presence a beta-1',6-linked disaccharide of 2,3-diamino-2,3-dideoxy-d-glucopyranose units. Two secondary unsaturated acyl chains are attached to the distal residue. The 1-position of the disaccharide is derivatized with an axial phosphate moiety, but the 4'-OH is unsubstituted. (1)H and (31)P NMR analyses revealed that the 1-phosphate group is methylated. Purified L. interrogans lipid A is inactive against human THP-1 cells but does stimulate tumor necrosis factor production by mouse RAW264.7 cells.
Risk of progression of advanced adenomas to colorectal cancer by age and sex: estimates based on 840 149 screening colonoscopies (2007)

Advanced adenoma transition rates are similar in both sexes, but there is a strong age gradient for both sexes. Our estimates of transition rates in older age groups are in line with previous estimates derived from small case series in the pre-colonoscopy era independent of age. However, our projections for younger age groups are considerably lower. These findings may have important implications for the design of CRC screening programmes.
Functional dissection of the promoter of the pollen‐specific gene NTP303 reveals a novel pollen‐specific, and conserved cis‐regulatory element (1995)

Regulatory elements within the promoter of the pollen-specific NTP303 gene from tobacco were analysed by transient and stable expression analyses. Analysis of precisely targeted mutations showed that the NTP303 promoter is not regulated by any of the previously described pollen-specific cis-regulatory elements. However, two adjacent regions from -103 to -86 bp and from -86 to -59 bp were shown to contain sequences which positively regulated the NTP303 promoter. Both of these regions were capable of driving pollen-specific expression from a heterologous promoter, independent of orientation and in an additive manner. The boundaries of the minimal, functional NTP303 promoter were determined to lie within the region -86 to -51 bp. The sequence AAATGA localized from -94 to -89 bp was identified as a novel cis-acting element, of which the TGA triplet was shown to comprise an active part. This element was shown to be completely conserved in the similarly regulated promoter of the Bp 10 gene from Brassica napus encoding a homologue of the NTP303 gene.
Stromal Cell-derived Factor-1α Associates with Heparan Sulfates through the First β-Strand of the Chemokine (1999)

Biological properties of chemokines are believed to be influenced by their association with glycosaminoglycans. Surface plasmon resonance kinetic analysis shows that the CXC chemokine stromal cell-derived factor-1alpha (SDF-1alpha), which binds the CXCR4 receptor, associates with heparin with an affinity constant of 38.4 nM (k(on) = 2.16 x 10(6) M(-1) s(-1) and k(off) = 0.083 x s(-1)). A modified SDF-1alpha (SDF-1 3/6) was generated by combined substitution of the basic cluster of residues Lys(24), His(25), and Lys(27) by Ser. SDF-1 3/6 conserves the global native structure and functional properties of SDF-1alpha, but it is unable to interact with sensor chip-immobilized heparin. The biological relevance of these in vitro findings was investigated. SDF-1alpha was unable to bind in a CXCR4-independent manner on epithelial cells that were treated with heparan sulfate (HS)-degrading enzymes or constitutively lack HS expression. The inability of SDF-1 3/6 to bind to cells underlines the importance of the identified basic cluster for the physiological interactions of SDF-1alpha with HS. Importantly, the amino-terminal domain of SDF-1alpha which is required for binding to, and activation of, CXCR4 remains exposed after binding to HS and is recognized by a neutralizing monoclonal antibody directed against the first residues of the chemokine. Overall, these findings indicate that the Lys(24), His(25), and Lys(27) cluster of residues forms, or is an essential part of, the HS-binding site which is distinct from that required for binding to, and signaling through, CXCR4.