gebhart/patrepeval huggingface dataset:
Cell-Free DNA and CXCL10 Derived from Bronchoalveolar Lavage Predict Lung Transplant Survival (2019)

Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid. A total of 60 BAL samples (20 with bronchiolitis obliterans (BOS), 20 with restrictive allograft syndrome (RAS), and 20 with stable allografts (STA)) were collected from 60 unique lung transplant patients; cfDNA and CXCL10 were measured by the ELISA-based KIT assay. Median cfDNA was significantly higher in BOS patients (6739 genomic equivalents (GE)/mL) versus STA (2920 GE/mL) and RAS (4174 GE/mL) (<i>p</i> < 0.01 all comparisons). Likelihood ratio tests revealed a significant association of overall survival with cfDNA (<i>p</i> = 0.0083), CXCL10 (<i>p</i> = 0.0146), and the interaction of cfDNA and CXCL10 (<i>p</i> = 0.023) based on multivariate Cox proportional hazards regression. Dichotomizing patients based on the median cfDNA level controlled for the mean level of CXCL10 revealed an over two-fold longer median overall survival time in patients with low levels of cfDNA. The KIT assay could predict allograft survival with superior performance compared with traditional biomarkers. These data support the pursuit of larger prospective studies to evaluate the predictive performance of cfDNA and CXCL10 prior to lung allograft failure.
Claudin-6 and Claudin-9 Function as Additional Coreceptors for Hepatitis C Virus (2007)

Hepatitis C virus (HCV) is a global challenge to public health. Several factors have been proven to be critical for HCV entry, including the newly identified claudin-1 (CLDN1). However, the mechanism of HCV entry is still obscure. Presently, among the 20 members of the claudin family identified in humans so far, CLDN1 has been the only member shown to be necessary for HCV entry. Recently, we discovered that Bel7402, an HCV-permissive cell line, does not express CLDN1 but expresses other members of claudin family. Among these claudins, CLDN9 was able to mediate HCV entry just as efficiently as CLDN1. We then examined if other members of the claudin family could mediate entry. We show that CLDN6 and CLDN9, but not CLDN2, CLDN3, CLDN4, CLDN7, CLDN11, CLDN12, CLDN15, CLDN17, and CLDN23, were able to mediate the entry of HCV into target cells. We found that CLDN6 and CLDN9 are expressed in the liver, the primary site of HCV replication. We also showed that CLDN6 and CLDN9, but not CLDN1, are expressed in peripheral blood mononuclear cells, an additional site of HCV replication. Through sequence comparison and mutagenesis studies, we show that residues N38 and V45 in the first extracellular loop (EL1) of CLDN9 are necessary for HCV entry.
Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection (2006)

The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n = 40) were older (44.7 +/- 16.3 vs. 36.0 +/- 14.3 years, P < .0017), less predominantly male (43% vs. 71%, P = .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P < .0001), less infected with subgenotype Ae (0% vs. 13%, P < .05), and more frequently with Bj (30% vs. 4%, P < .0001) than those with acute self-limited hepatitis (n = 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%, P < .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%, P = .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion, persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection.
Fidelity of replication of phage phi X174 DNA by DNA polymerase III holoenzyme: spontaneous mutation by misincorporation. (1979)

DNA from phi X174 is replicated in vitro with a fidelity similar to that found genetically. A mutation of TAG leads to TGG may be induced, however, by varying the concentrations of deoxynucleoside triphosphates, with a frequency proportional to [dGTP]2/[dATP]. This complex concentration dependence is consistent with the active participation of a proofreading mechanism that hydrolytically excises mismatched base pairs as they are formed. A simple kinetic analysis predicts that the frequency of misincorporation depends on the ratio of incorrect to correct deoxynucleoside triphosphates times the concentration of the next triphosphate in the sequence to be added. This suggests that spontaneous mutation by misincorporation depends crucially on the composition of the deoxynucleoside triphosphate pool.
Design and Synthesis of Hydrolytically Stable Multivalent Ligands Bearing Thiodigalactoside Analogues for Peanut Lectin and Human Galectin-3 Binding (2014)

Herein, we describe the design and synthesis of a novel family of hydrolytically stable glycoclusters bearing thiodigalactoside (TDG) analogues as recognition elements of β-galactoside binding lectins. The TDG analogue was synthesized by thioglycosylation of a 6-S-acetyl-α-D-glucosyl bromide with the isothiouronium salt of 2,3,4,6-tetra-O-acetyl-β-D-galactose. Further propargylation of the TDG analogue allowed the coupling to azido-functionalized oligosaccharide scaffolds through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) under microwave activation. The final mono-, di-, and tetravalent ligands were resistant to enzymatic hydrolisis by Escherichia coli β-galactosidase. Binding affinities to peanut agglutinin and human galectin-3 were measured by isothermal titration calorimetry which showed K(a) constants in the micromolar range as well as a multivalent effect. Monovalent ligand exhibited a binding affinity higher than that of thiodigalactoside. Docking studies performed with a model ligand on both β-galactoside binding lectins showed additional interactions between the triazole ring and lectin amino acid residues, suggesting a positive effect of this aromatic residue on the biological activity.
Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria (2006)

The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. Selective expression of FcRn in the epithelium is shown here to be associated with secretion of IgG into the lumen that allows for defense against an epithelium-associated pathogen (Citrobacter rodentium). This pathway of host resistance to a bacterial pathogen as mediated by FcRn involves retrieval of bacterial antigens from the lumen and initiation of adaptive immune responses in regional lymphoid structures. Epithelial-associated FcRn, through its ability to secrete and absorb IgG, may thus integrate luminal antigen encounters with systemic immune compartments and as such provide essential host defense and immunoregulatory functions at the mucosal surfaces.
Genetic, Structural, and Antigenic Analyses of Glycan Diversity in the O-Linked Protein Glycosylation Systems of HumanNeisseriaSpecies (2010)

Bacterial capsular polysaccharides and lipopolysaccharides are well-established ligands of innate and adaptive immune effectors and often exhibit structural and antigenic variability. Although many surface-localized glycoproteins have been identified in bacterial pathogens and symbionts, it not clear if and how selection impacts associated glycoform structure. Here, a systematic approach was devised to correlate gene repertoire with protein-associated glycoform structure in Neisseria species important to human health and disease. By manipulating the protein glycosylation (pgl) gene content and assessing the glycan structure by mass spectrometry and reactivity with monoclonal antibodies, it was established that protein-associated glycans are antigenically variable and that at least nine distinct glycoforms can be expressed in vitro. These studies also revealed that in addition to Neisseria gonorrhoeae strain N400, one other gonococcal strain and isolates of Neisseria meningitidis and Neisseria lactamica exhibit broad-spectrum O-linked protein glycosylation. Although a strong correlation between pgl gene content, glycoform expression, and serological profile was observed, there were significant exceptions, particularly with regard to levels of microheterogeneity. This work provides a technological platform for molecular serotyping of neisserial protein glycans and for elucidating pgl gene evolution.
Biodegradation of Viticulture Wastes byPleurotus:  A Source of Microbial and Human Food and Its Potential Use in Animal Feeding (2002)

The bioconversion of vineyard pruning and grape pomace by Pleurotus spp. using a solid state fermentation (SSF) was evaluated. Fruiting body production and chemical changes in the substrates after harvesting were measured. Biological efficiency and bioconversion ranged from 37.2 to 78.7% and from 16.7 to 38.8%, respectively. The best substrates for mycelial growth and mushroom yield were the mixtures with higher vineyard pruning content. Inclusion of pruning content had higher phenolic components and total sugars, better C/N ratio, and lower crude fat and total nitrogen than pomace. On the contrary, mycelium grew more slowly and scarcely in all treatments with 100% grape pomace. Moisture, protein, fat, and lignin contents were generally higher in mixtures with higher pomace proportion, whereas neutral detergent fiber, hemicellulose, and cellulose contents were higher with pruning content. Pleurotus strains may act depending on the availability of fiber fractions of substrate, and dynamic changes in digestion might occur as these fractions change during fungal growth. The recycling of viticulture residues through SSF by Pleurotus has great potential to produce human food and yields an available high-fiber feed for limited use in ruminants.
Expression of cytokine genes in human cardiac allografts: correlation of IL-6 and transforming growth factor-beta (TGF-β) with histological rejection (1993)

Cytokines may play critical roles in allograft rejection. Currently, a clear pattern of cytokine production that correlates with rejection has not emerged. Our preliminary studies suggested a trend toward increased IL-6 and TGF-beta gene expression in cardiac allografts during rejection. We have extended these studies using reverse transcriptase/polymerase chain reaction (RT/PCR) to detect the expression of IL-6, TGF-beta, and T cell receptor beta chain constant region (TCR-beta) genes in 21 additional consecutive myocardial biopsies obtained from six heart transplant patients and from five pre-transplant donor hearts. Cytokine gene expression was compared with histological diagnosis of rejection. There was strong correlation between IL-6 as well as TGF-beta gene expression, and histological rejection (6/8 biopsies with versus 0/7 without rejection (P = 0.006) and 7/9 biopsies with versus 0/7 without rejection (P = 0.003) respectively). Neither IL-6 nor TGF-beta transcripts were detected in any pre-transplant donor heart. TCR-beta chain mRNA was found in all allograft biopsies regardless of the presence of rejection, but was absent in pre-transplant donor hearts. Our results indicate that expression of IL-6 and TGF-beta is highly correlated with allograft rejection and thus may play an important role in regulation of cardiac allograft rejection. T cell infiltration of allografted myocardium is invariably detected by PCR regardless of histological rejection. The long-term functional significance of these cells in transplanted hearts needs further investigation.
Electroorganic chemistry. 39. Electroreductive elimination of phenolic hydroxyl groups and a new synthesis of olivetol (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectroorganic chemistry. 39. Electroreductive elimination of phenolic hydroxyl groups and a new synthesis of olivetolTatsuya Shono, Yoshihiro Matsumura, Kenji Tsubata, and Yoshihiro SugiharaCite this: J. Org. Chem. 1979, 44, 25, 4508–4511Publication Date (Print):December 1, 1979Publication History Published online1 May 2002Published inissue 1 December 1979https://pubs.acs.org/doi/10.1021/jo00393a010https://doi.org/10.1021/jo00393a010research-articleACS PublicationsRequest reuse permissionsArticle Views448Altmetric-Citations27LEARN 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
Effects of Aging on Crystallization, Dissolution and Absorption Characteristics of Amorphous Tolbutamide-2-Hydroxypropyl-.BETA.-cyclodextrin Complex. (2000)

The effects of storage on the crystallization, dissolution and absorption of tolbutamide from amorphous tolbutamide-2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) complex were investigated, in comparison with those of polyvinylpyrrolidone (PVP) solid dispersion. The amorphous solid complex of tolbutamide with HP-beta-CyD and the solid dispersion of tolbutamide with PVP were prepared by a spray-drying method. During storage, a stable form of tolbutamide (form I) was crystallized from the amorphous PVP dispersion, whereas a metastable form of tolbutamide (form II) was crystallized from the HP-beta-CyD complex. The dissolution rate of tolbutamide from both HP-beta-CyD complex and PVP dispersion was significantly faster than that of tolbutamide alone. However, the dissolution rate from the PVP dispersion markedly decreased with storage, because of the formation of slow dissolving form I crystals. On the other hand, the dissolution rate from the HP-beta-CyD complex was only slightly decreased due to the formation of fast dissolving formII crystals. These in vitro dissolution characteristics were clearly reflected in the in vivo absorption of tolbutamide and the glucose plasma level after oral administration in dogs. The results suggested that HP-beta-CyD is useful not only for converting crystalline tolbutamide to an amorphous substance, but also for maintaining the fast dissolution rate of the drug over a long period. Furthermore, the crystallization of drugs from CyD complexes, with storage, seemed to be different from that involving polymer excipients such as PVP.
Biomechanical Evaluation of Posterior and Anterior Lumbar Interbody Fusion Techniques (1998)

This study determined the biomechanical differences between anterior and posterior lumbar interbody fusion (ALIF and PLIF). Ten cadaveric spines were tested. Five specimens had ALIF and five had PLIF at L4-L5. Stabilization was performed with pedicle screws and rods (Cotrel-Dubboset, Sofamor-Danek, Memphis, TN, U.S.A.). Angular motion was measured in flexion, extension, bending, and torsion on the intact, instrumented, and "fused" specimens. Instrumentation alone caused a significant decrease in segmental motion in all loading modes (p < 0.01). After the simulated fusion procedures, all specimens were most stable in flexion, and significantly less stable in extension (p = 0.04). Comparing directly, ALIF was significant more stable in left torsion (p = 0.03) with trends in left bending (p = 0.08) and right torsion (p = 0.07). Thus, from a purely biomechanical perspective, ALIF appears to be slightly superior to PLIF.
Tissue Engineering with Chondrogenically Differentiated Human Embryonic Stem Cells (2007)

This study describes the development and application of a novel strategy to tissue engineer musculoskeletal cartilages with human embryonic stem cells (hESCs). This work expands the presently limited understanding of how to chondrogenically differentiate hESCs through the use of chondrogenic medium alone (CM) or CM with two growth factor regimens: transforming growth factor (TGF)-beta3 followed by TGF-beta1 plus insulin-like growth factor (IGF)-I or TGF-beta3 followed by bone morphogenic protein (BMP)-2. It also extends the use of the resulting chondrogenically differentiated cells for cartilage tissue engineering through a scaffoldless approach called self-assembly, which was conducted in two modes: with (a) embryoid bodies (EBs) or (b) a suspension of cells enzymatically dissociated from the EBs. Cells from two of the differentiation conditions (CM alone and TGF-beta3 followed by BMP-2) produced fibrocartilage-like constructs with high collagen I content, low collagen II content, relatively high total collagen content (up to 24% by dry weight), low sulfated glycosaminoglycan content (approximately 4% by dry weight), and tensile properties on the order of megapascals. In contrast, hESCs treated with TGF-beta3 followed by TGF-beta1 + IGF-I produced constructs with no collagen I. Results demonstrated significant differences among the differentiation conditions in terms of other biochemical and biomechanical properties of the self-assembled constructs, suggesting that distinct growth factor regimens differentially modulate the potential of the cells to produce cartilage. Furthermore, this work shows that self-assembly of cells obtained by enzymatic dissociation of EBs is superior to self-assembly of EBs. Overall, the results of this study raise the possibility of manipulating the characteristics of hESC-generated tissue toward specific musculoskeletal cartilage applications.
Restriction landmark genomic scanning method and its various applications (1993)

We have developed a new genome scanning method (restriction landmark genomic scanning (RLGS), based on the new concept of using restriction enzyme sites as landmarks. RLGS employs direct end labeling of the genomic DNA digested with a restriction enzyme and two-dimensional electrophoresis with high-resolution. Its advantages are: (i) high-speed scanning ability, allowing simultaneous scanning of thousands of restriction landmarks; (ii) extension of the scanning field using different kinds of landmarks in an additional series of electrophoresis; (iii) application to any type of organism because of direct-labeling of restriction enzyme sites and no hybridization procedure; and (iv) reflection of the copy number of the restriction landmark by the spot intensity which enables distinction of haploid and diploid genomic DNAs. The RLGS method has various applications because it can be used to scan for physical genomic DNA states, such as amplification, deletion and methylation. The copy number of the locus of a restriction landmark can be estimated by the spot intensity to find either an amplified or deleted region. The methylation state of genomic DNA can also be discovered by use of a methylation-sensitive restriction enzyme sites as a restriction landmark (restriction landmark genomic scanning for screening methylated sites, RLGS-M). This article introduces the basic principle of RLGS and its applications to the analysis of cancer, mouse mutant DNAs and tissue-specific methylation, showing the usefulness of RLGS for a variety of biological fields.
The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations (2005)

Mitochondria are cellular energy factories that generate ATP via the reaction of hydrocarbons with oxygen. Every human cell contains hundreds of mitochondria, and each mitochondrion contains multiple copies of mitochondrial DNA (mtDNA). The ancestry of the mitochondrial genome can be traced to early eubacteria, and it is therefore unexpected that this organelle may have a major role in governing the pace of human aging. Three recent papers (1–3) plus a work published in a recent issue of PNAS (4) have demonstrated that accelerating the mtDNA mutation rate can result in some features suggestive of premature aging, consistent with the view that loss of mitochondrial function is a major causal factor in aging.

mtDNA polymerase (Pol-γ) is the only DNA polymerase that is known to be targeted to and that resides in mitochondria (5). In the absence of other known mtDNA polymerases, it is assumed that Pol-γ is responsible for all aspects of mtDNA synthesis, including replication of the mitochondrial genome and repair of DNA damage. As is the case for many other DNA polymerases, the high fidelity of Pol-γ derives from both selection for the correct incoming nucleotide and excision of misincorporated nucleotides by a 3′ → 5′ exonucleolytic proofreading activity (6). Elimination of proofreading by replacement of critical aspartic acid residues in the exonuclease domain with alanine increases misincorporation; in vitro , this misincorporation is manifested predominantly as single base substitutions (7). Both the Larsson (1) and Prolla (2) groups replaced in embryonic stem cells POLG, the …