gebhart/patrepeval huggingface dataset:
Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer (2013)

Genome-wide DNA hypomethylation and gene hypermethylation play important roles in instability and carcino-genesis. Methylation in long interspersed nucleotide element 1 (LINE-1) is a good indicator of the global DNA methylation level within a cell. Slit homolog 2 (SLIT2), myelin and lymphocyte protein gene (MAL) and insulin-like growth factor binding protein 7 (IGFBP7) are known to be hypermethylated in various malignancies. The aim of the present study was to assess the precise methylation levels of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer (NSCLC) using a pyrosequencing assay. Methylation of all regions was examined in 56 primary NSCLCs using a pyrosequencing assay. Changes in mRNA expression levels of SLIT2, MAL and IGFBP7 were measured before and after treatment with a demethylating agent. Methylation of these genes was also examined in 9 lung cancer cell lines using RT-PCR and a pyrosequencing assay. Frequencies of hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7, defined by predetermined cut off values, were 55, 64, 46 and 54% in NSCLCs, respectively and exhibited tumor-specific features. The hypermethylation of all genes was well correlated with changes in expression. The methylation level and frequency of MAL were significantly higher in smokers and in patients without EGFR mutations. Through accurate measurement of methylation levels using pyrosequencing, hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7 were frequently detected in NSCLCs and associated with various clinical features. Analysis of the methylation profiles of these genes may, therefore, provide novel opportunities for the therapy of NSCLCs.
Synthesis of Kojidextrins and Their Protein Conjugates. Incidence of Steric Mismatch in Oligosaccharide Synthesis (1997)

Kojidextrins are biologically important oligosaccharides that are involved in many physiological processes including protein glycosylation and bacterial growth. As part of our project to explore the role kojidextrins may play in bacterial pathogenesis, here we report synthetic routes to kojibiose (54), -triose (58), -tetraose (64), and -pentaose (69) equipped with alpha-linked (hydrazinocarbonyl)pentyl aglycon, using linear and convergent strategies. In the search for a rapid convergent strategy for the construction of extended kojidextrins, four kojibiose donors (1-4) were synthesized that contain acyl- and ether-type protecting groups in various ratios. These were tested to probe the influence of diverse protecting group assemblies on their glycosyl donor ability. Attempted condensation of these donors with kojitriose and -tetraose acceptors failed to give the desired products apparently because of steric mismatch between the donor and the acceptor moieties. A one-pot procedure was developed for the covalent attachment of the synthetic saccharides through their hydrazido group to human serum albumin (HSA) using Tietze's squarate method to give neoglycoproteins containing up to 28 saccharide units per HSA.
Targeting RNA with Small Molecules (2008)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTTargeting RNA with Small MoleculesJason R. Thomas and Paul J. HergenrotherView Author Information Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, Illinois 61822 Cite this: Chem. Rev. 2008, 108, 4, 1171–1224Publication Date (Web):March 25, 2008Publication History Received7 September 2007Published online25 March 2008Published inissue 1 April 2008https://pubs.acs.org/doi/10.1021/cr0681546https://doi.org/10.1021/cr0681546research-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views10233Altmetric-Citations546LEARN 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 SUBJECTS:Carbohydrates,Genetics,Ligands,Screening assays,Small molecules Get e-Alerts
Identification and Association of Polymorphisms in the Interleukin-13 Gene with Asthma and Atopy in a Dutch Population (2001)

Asthma and atopy are related conditions that may share similar genetic susceptibility. Linkage studies have identified a region on chromosome 5q that contains biologic candidates for both asthma and atopy phenotypes, including several proinflammatory cytokines. Interleukin (IL)-13, one of the candidate genes in the region, is directly involved in the regulation of immunoglobulin E and has been associated with both asthma and atopy. We sought to identify new polymorphisms in the IL-13 gene, and evaluated the involvement of a subset of these variants in asthma and atopy in a case-control study using probands and spouses from a Dutch asthma family study. IL-13 was sequenced in 20 probands and 20 unaffected spouses, and 10 polymorphisms were identified, four novel and six previously reported. Three single nucleotide (nt) polymorphisms (SNPs) were detected in the 5'-promoter region, two in intron 1, and five in exon 4. Only one of the exon 4 SNPs resulted in an amino-acid change (Arg130Gln). We analyzed three SNPs in IL-13 in an extended group of 184 probands and their spouses: one in the promoter region (-1111), the Arg130Gln (nt position 4257), and a 3' untranslated region SNP (nt position 4738). The most significant associations were observed to asthma (P = 0.005), bronchial hyperresponsiveness (P = 0.003), and skin-test responsiveness (P = 0.03) with the -1111 promoter. These results provide evidence that variation in the IL-13 gene is involved in the pathogenesis of asthma and atopy. Further investigation is required to determine which specific alleles or combination of alleles contribute to these phenotypes, and the possible downstream effects of the resulting change in IL-13 levels or activity.
Application of Real-time Polymerase Chain Reaction (RT-PCR) (2006)

The real-time polymerase chain reaction (RT-PCR), also called quantitative real-time polymerase chain reaction (QRT-PCR) or kinetic polymerase chain reaction (kPCR), is a technique used to simultaneously quantify and amplify a DNA molecule. It is used to determine whether a specific DNA sequence is present in the sample; and if it is present, the number of copies in the sample. It is the real-time version of quantitative polymerase chain reaction (qPCR), itself a modification of polymerase chain reaction (PCR). The procedure of RT-PCR follows the regular PCR procedure, but the DNA is quantified after each round of amplification. Two common methods of quantification are the use of fluorescent dyes that intercalate with double-strand DNA, and modified DNA oligonucleotide probes that fluoresce when hybridized with a complementary DNA. RT-PCR could be combined with reverse transcription polymerase chain reaction to quantify messenger RNA (mRNA) at a particular time for in a particular cell or tissue type. (The Journal of American Science. 2006;2(3):1-15).
An Insulin-like Signaling Pathway Affects Both Longevity and Reproduction in Caenorhabditis elegans (1998)

Mutations in daf-2 and age-1 cause a dramatic increase in longevity as well as developmental arrest at the dauer diapause stage in Caenorhabditis elegans. daf-2 and age-1 encode components of an insulin-like signaling pathway. Both daf-2 and age-1 act at a similar point in the genetic epistasis pathway for dauer arrest and longevity and regulate the activity of the daf-16 gene. Mutations in daf-16 cause a dauer-defective phenotype and are epistatic to the diapause arrest and life span extension phenotypes of daf-2 and age-1 mutants. Here we show that mutations in this pathway also affect fertility and embryonic development. Weak daf-2 alleles, and maternally rescued age-1 alleles that cause life span extension but do not arrest at the dauer stage, also reduce fertility and viability. We find that age-1(hx546) has reduced both maternal and zygotic age-1 activity. daf-16 mutations suppress all of the daf-2 and age-1 phenotypes, including dauer arrest, life span extension, reduced fertility, and viability defects. These data show that insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that DAF-16 transduces these signals. The regulation of fertility, life span, and metabolism by an insulin-like signaling pathway is similar to the endocrine regulation of metabolism and fertility by mammalian insulin signaling.
Detecting Mechanoluminescence From ZnS:Mn Powder Using a High Speed Camera (2013)

There are a number of techniques currently being used for damage detection and monitoring of civil, aerospace, and military structures and aircraft. However, the major drawbacks of the current techniques are that they do not provide in-situ and distributed sensing. In addition, the associated cost resulting from the downtime required for periodic non-destructive inspections can be very high for aerospace structures and nearly impossible for remote Lunar habitats. Mechanoluminescent-based sensor systems may be able to overcome these challenges as they have the potential for wireless, in-situ, and distributed sensing that can enable real-time continuous monitoring of both the magnitude and location of damage with respect to the host structure. They can also be used as stress, fracture, and damage sensors. However, if these sensors are to become a reality, the sensing of these impacts must move out of the lab setting using expensive light detectors and oscilloscopes. Instead, inexpensive robust cameras must be utilized to reduce the cost of sensors and make them more portable. This research explores the use of replacing the typical light detector and oscilloscope with a high speed camera. The results indicate that a high-speed camera can be used to replace the typical lab setup and yield the same results. Thus, indicating that it is possible to migrate from light detectors to inexpensive cameras in the future.
Effect of portal hypertension on splenic blood flow, intrasplenic extravasation and systemic blood pressure (2003)

We have previously shown that intrasplenic fluid extravasation is important in controlling blood volume. We proposed that, because the splenic vein flows in the portal vein, portal hypertension would increase splenic venous pressure and thus increase intrasplenic microvascular pressure and fluid extravasation. Given that the rat spleen has no capacity to store/release blood, intrasplenic fluid extravasation can be estimated by measuring the difference between splenic arterial inflow and venous outflow. In anesthetized rats, partial ligation of the portal vein rostral to the junction with the splenic vein caused portal venous pressure to rise from 4.5 +/- 0.5 to 12.0 +/- 0.9 mmHg (n = 6); there was no change in portal venous pressure downstream of the ligation, although blood flow in the liver fell. Splenic arterial flow did not change, but the arteriovenous flow differential increased from 0.8 +/- 0.3 to 1.2 +/- 0.1 ml/min (n = 6), and splenic venous hematocrit rose. Mean arterial pressure fell (101 +/- 5.5 to 95 +/- 4 mmHg). Splenic afferent nerve activity increased (5.6 +/- 0.9 to 16.2 +/- 0.7 spikes/s, n = 5). Contrary to our hypothesis, partial ligation of the portal vein caudal to the junction with the splenic vein (same increase in portal venous pressure but no increase in splenic venous pressure) also caused the splenic arteriovenous flow differential to increase (0.6 +/- 0.1 to 1.0 +/- 0.2 ml/min; n = 8). The increase in intrasplenic fluid efflux and the fall in mean arterial pressure after rostral portal vein ligation were abolished by splenic denervation. We propose there to be an intestinal/hepatic/splenic reflex pathway, through which is mediated the changes in intrasplenic extravasation and systemic blood pressure observed during portal hypertension.
External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria (1999)

Recent work in our research consortium has raised internal validity concerns regarding the current IASP criteria for Complex Regional Pain Syndrome (CRPS), suggesting problems with inadequate sensitivity and specificity. The current study explored the external validity of these IASP criteria for CRPS. A standardized evaluation of signs and symptoms of CRPS was conducted by study physicians in 117 patients meeting IASP criteria for CRPS, and 43 patients experiencing neuropathic pain with established non-CRPS etiology (e.g. diabetic neuropathy, post-herpetic neuralgia). Multiple discriminant function analyses were used to test the ability of the IASP diagnostic criteria and decision rules, as well as proposed research modifications of these criteria, to discriminate between CRPS patients and those experiencing non-CRPS neuropathic pain. Current IASP criteria and decision rules (e.g. signs or symptoms of edema, or color changes or sweating changes satisfy criterion 3) discriminated significantly between groups (P < 0.001). However, although sensitivity was quite high (0.98), specificity was poor (0.36), and a positive diagnosis of CRPS was likely to be correct in as few as 40% of cases. Empirically-based research modifications to the criteria, which are more comprehensive and require presence of signs and symptoms, were also tested. These modified criteria were also able to discriminate significantly, between the CRPS and non-CRPS groups (P < 0.001). A decision rule, requiring at least two sign categories and four symptom categories to be positive optimized diagnostic efficiency, with a diagnosis of CRPS likely to be accurate in up to 84% of cases, and a diagnosis of non-CRPS neuropathic pain likely to be accurate in up to 88% of cases. These results indicate that the current IASP criteria for CRPS have inadequate specificity and are likely to lead to overdiagnosis. Proposed modifications to these criteria substantially improve their external validity and merit further evaluation.
Alterations of Hippocampal Glucose Metabolism by Even versus Uneven Medium Chain Triglycerides (2013)

Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain.
Core fucosylation of E‐cadherin enhances cell–cell adhesion in human colon carcinoma WiDr cells (2009)

Alpha1,6-fucosyltransferase (Fut8), an enzyme that catalyzes the introduction of alpha1,6 core fucose to the innermost N-acetylglucosamine residue of the N-glycan, has been implicated in the development, immune system, and tumorigenesis. We found that alpha1,6-fucosyltransferase and E-cadherin expression levels are significantly elevated in primary colorectal cancer samples. Interestingly, low molecular weight population of E-cadherin appeared as well as normal sized E-cadherin in cancer samples. To investigate the correlation between alpha1,6-fucosyltransferase and E-cadherin expression, we introduced alpha1,6-fucosyltransferase in WiDr human colon carcinoma cells. It was revealed that the low molecular weight population of E-cadherin was significantly increased in alpha1,6-fucosyltransferase-transfected WiDr cells in dense culture, which resulted in an enhancement in cell-cell adhesion. The transfection of mutated alpha1,6-fucosyltransferase with no enzymatic activity had no effect on E-cadherin expression, indicating that core fucosylation is involved in the phenomena. In alpha1,6-fucosyltransferase knock down mouse pancreatic acinar cell carcinoma TGP49 cells, the expression of E-cadherin and E-cadherin dependent cell-cell adhesion was decreased. The introduction of alpha1,6-fucosyltransferase into kidney epithelial cells from alpha1,6-fucosyltransferase(-/-) mice restored the expression of E-cadherin and E-cadherin-dependent cell-cell adhesion. Based on the results of lectin blotting, peptide N-glycosidase F treatment, and pulse-chase studies, it was demonstrated that the low molecular weight population of E-cadherin contains peptide N-glycosidase F insensitive sugar chains, and the turnover rate of E-cadherin was reduced in alpha1,6-Fucosyltransferase transfectants. Thus, it was suggested that core fucosylation regulates the processing of oligosaccharides and turnover of E-cadherin. These results suggest a possible role of core fucosylation in the regulation of cell-cell adhesion in cancer.
NMR Observation of Selected Segments in a Larger Protein:  Central-Segment Isotope Labeling through Intein-Mediated Ligation (1999)

Peptide segments in a protein, which can include an active site of interest or be a series of parts constituting the entire structure, are now selectively observed by nuclear magnetic resonance (NMR) spectroscopy using samples prepared by the intein-mediated ligation method. Two separate inteins were used to ligate NMR-transparent segments to both the ends of an NMR-visible segment, producing a partly visible intact protein molecule. The (15)N-(1)H correlation spectrum of a 370-residue maltose binding protein labeled with (15)N at a continuous segment comprising residues Gly(101)-Ser(238) showed the essential elimination of signal overlapping, the signals being at the same positions as for the uniformly labeled sample. This method will allow structural analysis by NMR of over 50-kDa proteins in combination with contemporary NMR techniques suppressing the signal decays of larger proteins.
R Factor Transfer in Rhizobium leguminosarum (1974)

SUMMARY: R factors of the compatibility class P were transferred between strains of Escherichia coli k12 and Rhizobium leguminosarum. These R factors were stable in R. leguminosarum and conferred similar levels of antibiotic resistance to those in the corresponding R+ E. coli k12 hosts, with the exception of carbenicillin resistance which was greatly reduced. Transfer between R. leguminosarum strains was by conjugation and was stimulated by conditions favouring spheroplast formation. R factor mediated recombination could not be demonstrated.
Tissue engineering of urinary organs (2000)

Tissue engineering can serve as an alternative treatment for a malfunctioning or lost organ. Isolated and expanded cells adhere to a temporary scaffold, proliferate, and secrete their own extracellular matrices (ECM) replacing the biodegrading scaffold. The genitourinary system, composed of the kidney, ureter, bladder, urethra, and genital organs, is exposed to a variety of possible injury sites from the time of fetal development. All the urinary organs are mainly composed of smooth muscle and uroepithelial cells and which may be approached by tissue engineering techniques. A large number of materials, including naturally-derived and synthetic polymers have been utilized to fabricate prostheses for the genitourinary system. Usually, whenever there is a lack of native urologic tissue, reconstruction is considered with native non-urologic tissue, such as, gastrointestinal segments, or skin or mucosa from multiple body sites. Engineering tissues using selective cell transplantation may provide a means to create functional new genitourinary tissues. This review concerns urinary tissues reconstructed with bladder uroepithelial cells and smooth muscle cells (SMCs) implanted on biodegradable polymer matrices.
Clearance and binding of two electrophoretic “fast” forms of human alpha 2-macroglobulin. (1981)

These studies explore the role of conformational change and exposed carbohydrate residues in the clearance of alpha 2-macroglobulin-trypsin (alpha 2M-T) complexes in the mouse. Human alpha 2-macroglobulin (alpha 2M) was purified and demonstrated to be homogeneous in the electrophoretic "slow" form. Two conformationally altered derivatives, alpha 2M-T and alpha 2-macroglobulin-methylamine (alpha 2M-MeNH2), were prepared and demonstrated to exist in the electrophoretic "fast" form. Radiolabeled alpha 2M-T and alpha 2M-MeNH2 were cleared rapidly with a half-life of 2-4 min following injection into mice. Radiolabeled native alpha 2M, however, remained in the circulation with a half-life of several hours. Both alpha 2M-T and alpha 2M-MeNH2 bound specifically to mouse peritoneal macrophages at 4 degrees C and occupancy of receptor sites increased with increasing time and radioligand concentration. Excess amounts of unlabeled alpha 2M-T or alpha 2M-MeNH2 cross-completed with trace amounts of the other in both clearance studies and binding assays, indicating that both derivatives were removed by the same receptor pathway. The clearance and binding of alpha 2M-T and alpha 2M-MeNH2 were not inhibited by excess amounts of unlabeled asialoorosomucoid, fucosyl-bovine serum albumin, mannosyl-BSA, or N-acetylglucosaminyl-BSA. Our results indicate that the clearance pathway removing alpha 2M-T complexes from the circulation recognizes a fundamental conformational change in alpha 2M secondary to protease binding, which can also be induced by exposure to methylamine. Therefore, other chemical or physical alterations that occur in alpha 2M upon binding trypsin, apart from the conformational change also present in alpha 2M-MeNH2, do not seem necessary for the recognition of alpha 2M-T by cells in the clearance pathway. In addition, this pathway appears distinct from several systems already described mediating clearance of glycoproteins through recognition of terminal galactose, fucose, N-acetylglucosamine, or mannose on oligosaccharide side chains.