tbuckley/cabot-search huggingface dataset:
More Genes or More Taxa? The Relative Contribution of Gene Number and Taxon Number to Phylogenetic Accuracy
Authors: Antonis Rokas, Sean B. Carroll
Journal: Molecular Biology and Evolution (2005)

The relative contribution of taxon number and gene number to accuracy in phylogenetic inference is a major issue in phylogenetics and of central importance to the choice of experimental strategies for the successful reconstruction of a broad sketch of the tree of life. Maximization of the number of taxa sampled is the strategy favored by most phylogeneticists, although its necessity remains the subject of debate. Vast increases in gene number are now possible due to advances in genomics, but large numbers of genes will be available for only modest numbers of taxa, raising the question of whether such genome-scale phylogenies will be robust to the addition of taxa. To examine the relative benefit of increasing taxon number or gene number to phylogenetic accuracy, we have developed an assay that utilizes the symmetric difference tree distance as a measure of phylogenetic accuracy. We have applied this assay to a genome-scale data matrix containing 106 genes from 14 yeast species. Our results show that increasing taxon number correlates with a slight decrease in phylogenetic accuracy. In contrast, increasing gene number has a significant positive effect on phylogenetic accuracy. Analyses of an additional taxon-rich data matrix from the same yeast clade show that taxon number does not have a significant effect on phylogenetic accuracy. The positive effect of gene number and the lack of effect of taxon number on phylogenetic accuracy are also corroborated by analyses of two data matrices from mammals and angiosperm plants, respectively. We conclude that, for typical data sets, the number of genes utilized may be a more important determinant of phylogenetic accuracy than taxon number.
Circulating leukocyte integrin expression in Wegener's granulomatosis.
Authors: H Haller, J Eichhorn, K Pieper, U Göbel, F C Luft
Journal: Journal of the American Society of Nephrology (1996)

Leukocyte adhesion and infiltration are important in the pathogenesis of Wegener's granulomatosis (WG). We tested the hypothesis that the expression of the beta 1-chain integrin VLA-4 (CD49d/CD29) and the beta 2-chain integrins LFA-1 (CD11a/CD18), Mac-1 (CD11a/CD18), and gp150,95 (CD11c/CD18) is increased on leukocytes in patients with active WG. Fifteen patients with active WG as defined by positive antineutrophil cytoplasmic autoantibody (cANCA) titers and biopsy, 30 patients with WG in remission as defined by negative cANCA titers and/or immunosuppressive therapy, 25 normal control subjects, and 12 patients with other inflammatory renal and systemic diseases were studied. Surface expression of LFA-1, Mac-1, p150, 95, and VLA-4 on neutrophils, lymphocytes, and monocytes was measured by fluorescent antibody cell sorting with monoclonal antibodies against CD11a, CD11b, CD11c, CD18, CD49d, and CD29 respectively. Immunocytochemistry and confocal microscopy were also utilized. beta 1 (CD29) and beta 2 (CD18) integrin subunit expression on neutrophils, monocytes, and lymphocytes from patients with acute WG was significantly increased compared with healthy persons and compared with patients with treated vasculitis. Furthermore, the alpha-integrin subunit CD11b expression was increased on granulocytes and monocytes, but not on lymphocytes. Finally, the alpha-integrin subunit CD11a expression was increased on monocytes. Immunocytochemistry showed that the increased immunoreactivity on neutrophils was evenly distributed on the plasma membrane and in the cytosol. Immunosuppression resulted in decreased expression of the beta 1 and beta 2-integrin subunits. It was concluded that the integrin adhesion molecules, particularly Mac-1 (CD11b/CD18), are upregulated on leukocytes in active WG. This finding suggests a role for integrin expression in the pathogenesis of WG and a possible clue for treatment.
Athermal Division and Selective Suture Ligation of the Dorsal Vein Complex During Robot-Assisted Laparoscopic Radical Prostatectomy: Description of Technique and Outcomes
Authors: Yin Lei, Mehrdad Alemozaffar, Stephen B. Williams, Nathanael Hevelone, Stuart R. Lipsitz, Blakely A. Plaster, Channa A. Amarasekera, William D. Ulmer, Andy C. Huang, Keith J. Kowalczyk, Jim C. Hu
Journal: European Urology (2010)
Loss of Rho GDIα and Resistance to Tamoxifen via Effects on Estrogen Receptor α
Authors: Ines Barone, Lauren Brusco, Guowei Gu, Jennifer Selever, Amanda Beyer, Kyle R. Covington, Anna Tsimelzon, Tao Wang, Susan G. Hilsenbeck, Gary C. Chamness, Sebastiano Andò, Suzanne A.W. Fuqua
Journal: JNCI Journal of the National Cancer Institute (2011)

Estrogen receptor (ER) α is a successful therapeutic target in breast cancer, but patients eventually develop resistance to antiestrogens such as tamoxifen.
Adenosine Receptor–Mediated Adhesion of Endothelial Progenitors to Cardiac Microvascular Endothelial Cells
Authors: Sergey Ryzhov, Nataliya V. Solenkova, Anna E. Goldstein, Mathias Lamparter, Todd Fleenor, Pampee P. Young, James P. Greelish, John G. Byrne, Douglas E. Vaughan, Italo Biaggioni, Antonis K. Hatzopoulos, Igor Feoktistov
Journal: Circulation Research (2007)

Intracoronary delivery of endothelial progenitor cells (EPCs) is an emerging concept for the treatment of cardiovascular disease. Enhancement of EPC adhesion to vascular endothelium could improve cell retention within targeted organs. Because extracellular adenosine is elevated at sites of ischemia and stimulates neovascularization, we examined the potential role of adenosine in augmenting EPC retention to cardiac microvascular endothelium. Stimulation of adenosine receptors in murine embryonic EPCs (eEPCs) and cardiac endothelial cells (cECs) rapidly, within minutes, increased eEPC adhesion to cECs under static and flow conditions. Similarly, adhesion of human adult culture-expanded EPCs to human cECs was increased by stimulation of adenosine receptors. Furthermore, adenosine increased eEPC retention in isolated mouse hearts perfused with eEPCs. We determined that eEPCs and cECs preferentially express functional A 1 and A 2B adenosine receptor subtypes, respectively, and that both subtypes are involved in the regulation of eEPC adhesion to cECs. We documented that the interaction between P-selectin and its ligand (P-selectin glycoprotein ligand-1) plays a role in adenosine-dependent eEPC adhesion to cECs and that stimulation of adenosine receptors in cECs induces rapid cell surface expression of P-selectin. Our results suggest a role for adenosine in vasculogenesis and its potential use to stimulate engraftment in cell-based therapies.
Treatment of Hepatitis B e Antigen–Positive Chronic Hepatitis with Telbivudine or Adefovir
Authors: Henry L.Y. Chan
Journal: Annals of Internal Medicine (2007)

Background: The efficacy of nucleoside and nucleotide analogues for hepatitis B has been linked to the magnitude and durability of hepatitis B virus (HBV) suppression. Objective: To compare the antiviral efficacy of telbivudine and adefovir dipivoxil, and the effects of switching from adefovir to telbivudine, in hepatitis B e antigen (HBeAg)–positive patients with chronic hepatitis B. Design: Randomized, controlled, open-label trial. Setting: 16 outpatient clinics. Patients: 135 treatment-naive, HBeAg-positive adults with chronic hepatitis B. Intervention: Patients were randomly assigned in a 1:1:1 ratio to 52 weeks of telbivudine (group A) or adefovir (group B), or 24 weeks of adefovir and then telbivudine for the remaining 28 weeks (group C). One hundred thirty-one patients completed 52 weeks of treatment. Measurements: The primary efficacy comparison was serum HBV DNA reduction at week 24, with a secondary comparison at week 52. Results: At week 24, mean HBV DNA reduction was greater in group A than in pooled groups B and C (−6.30 vs. −4.97 log10 copies/mL; difference, −1.33 log10 copies/mL [95% CI, −1.99 to −0.66 log10 copies/mL]; P < 0.001), and more patients in group A were polymerase chain reaction–negative (39% vs. 12%; odds ratio, 4.46 [CI, 1.86 to 10.72]; P = 0.001). At week 52, the mean residual HBV DNA level was lower in group A and group C than in group B (3.01 log10 copies/mL [group A] and 3.02 log10 copies/mL [group C] vs. 4.00 log10 copies/mL [group B]; difference, −0.99 log10 copies/mL [CI, −1.67 to −0.32 log10 copies/mL] and −0.98 log10 copies/mL [CI, −1.64 to −0.32 log10 copies/mL]; P = 0.004). Adverse events were similar across groups; the most common were upper respiratory symptoms, headache, back pain, and diarrhea. Limitations: The trial was open-label and was not of sufficient size or duration to compare clinical outcomes and long-term efficacy. Conclusion: Telbivudine demonstrated greater and more consistent HBV DNA suppression than adefovir after 24 weeks of treatment. After 52 weeks, HBV DNA suppression was greater in patients who had received continuous telbivudine or were switched to telbivudine after 24 weeks than in those who received continuous adefovir.
Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity.
Authors: C M Celluzzi, J I Mayordomo, W J Storkus, M T Lotze, L D Falo
Journal: The Journal of Experimental Medicine (1996)

Cytotoxic T lymphocytes (CTLs) are a critical component of the immune response to tumors. Tumor-derived peptide antigens targeted by CTLs are being defined for several human tumors and are potential immunogens for the induction of specific antitumor immunity. Dendritic cells (DC) are potent antigen-presenting cells (APCs) capable of priming CTL responses in vivo. Here we show that major histocompatibility complex class I-presented peptide antigen pulsed onto dendritic APCs induces protective immunity to lethal challenge by a tumor transfected with the antigen gene. The immunity is antigen specific, requiring expression of the antigen gene by the tumor target, and is eliminated by in vivo depletion of CD8+ T cells. Furthermore, mice that have rejected the transfected tumor are protected from subsequent challenge with the untransfected parent tumor. These results suggest that immunization strategies using antigen-pulsed DC may be useful for inducing tumor-specific immune responses.
European Community Respiratory Health Survey calibration project of dosimeter driving pressures
Authors: R.J. Ward, C. Ward, D.P. Johns, B. Skoric, M. Abramson, E.H. Walters
Journal: European Respiratory Journal (2002)

Two potential sources of systematic variation in output from Mefar dosimeters, the system used in the European Community Respiratory Health Survey (ECRHS) study have been evaluated: individual nebulizer characteristics and dosimeter driving pressure. Output variation from 366 new nebulizers produced in two batches for the second ECRHS were evaluated, using a solute tracer method, at a fixed driving pressure. The relationship between dosimeter driving pressure was then characterized and between-centre variation in dosimeter driving pressure was evaluated in an Internet-based survey. A systematic difference between nebulizers manufactured in the two batches was identified. Batch one had a mean±sd output of 7.0±0.8 mg·s<sup>−1</sup> and batch two, 6.3±0.7 mg·s<sup>−1</sup> (p&lt;0.005). There was a wide range of driving pressures generated by Mefar dosimeters as set, ranging between 70–245 kPa, with most outside the quoted manufacturer9s specification of 180±5%. Nebulizer output was confirmed as linearly related to dosimeter driving pressure (coefficient of determination (R<sup>2</sup>)=0.99, output=0.0377×driving pressure–0.4151). The range in driving pressures observed was estimated as consistent with a variation of about one doubling in the provocative dose causing a 20% fall in forced expiratory volume in one second. Systematic variation has been identified that constitutes potentially significant confounders for between-centre comparisons of airway responsiveness in the European Community Respiratory Health Survey, with the dosimeter driving pressure representing the most serious issue. This work confirms the need for appropriate quality control of both nebulizer output and dosimeter driving pressure, in laboratories undertaking field measurements of airway responsiveness. In particular, appropriate data on driving pressures need to be collected and factored into between-centre comparisons. Comprehensive collection of such data to optimize quality control is practicable and has been instigated by the organizing committee for the European Community Respiratory Health Survey II.
Heterogeneous Patterns of <i>CEBPα</i> Mutation Status in the Progression of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia to Acute Myelogenous Leukemia
Authors: Lee-Yung Shih, Chein-Fuang Huang, Tung-Liang Lin, Jin-Hou Wu, Po-Nan Wang, Po Dunn, Ming-Chung Kuo, Tzung-Chih Tang
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We aimed to assess the role of CEBPα mutations in the progression of myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML) and their cooperating mutations. Experimental Design: Mutational analysis of CEBPα with direct sequencing for each PCR product was done on matched bone marrow samples obtained from 50 adult patients with MDS at diagnosis and at AML transformation. Cloning analysis was used to determine the allelic distribution. Results: CEBPα mutations were identified in four patients at diagnosis of MDS, including one with refractory anemia with excess blasts and three with chronic myelomonocytic leukemia. At AML transformation, three patients retained the identical mutant clones as their initial diagnosis, three acquired the mutations, and one lost CEBPα mutation when she gained FLT3/ITD mutation. Together, seven patients had CEBPα mutations throughout the disease course; four patients had NH2-terminal mutations resulting in a frameshift and truncation of the protein, three of them had two different mutations either on the same alleles or on different alleles, two had missense mutations, and one had a deletion in the basic region leucine zipper domain. Except for one with coexistence of N-ras mutation, no sample harbored cooperating mutations with FLT3 or N-ras genes. CEBPα mutations had no influence on the time to AML progression or overall survival. Conclusions: Our results show that CEBPα mutations play a role in a subset of patients with MDS, especially in chronic myelomonocytic leukemia. The mutation status was heterogeneous, exhibiting identical clone, clonal change, or clonal evolution during the progression to AML.
A Quick and Simple Method for Blood-sugar Estimation
Authors: J. Lee
Journal: BMJ (1954)

Without blood-sugar estimations the recognition and proper treatment of hyperglycaemia and hypoglycaemia may be difficult.Emergencies may arise in domiciliary practice or in hospital at a time when no routine labora- tory facilities are available.A simple method of blood- sugar estimation which can be carried out in a few minutes would therefore be useful: such a method is described here.The method presented is that originally described by Sumner (1921, 1924-5, 1925), who utilized the change in colour from yellow to red when the sugar in a de- proteinized blood filtrate is heated with dinitrosalicylic acid in alkaline solution.The modifications effected are essentially that the scale is reduced to the micro level and that dinitrosalicylic acid itself is used as a protein preci- pitant, in which capacity it is very efficient.The excess of the acid in the filtrate is adequate for the subsequent development of colour.Finally, a set of permanent artificial colour standards has been devised.*Experimental Proportion of Reagents.-0.2 ml. of blood was added to
Endothelial Cells of the Human Microvasculature Express Epidermal Fatty Acid–Binding Protein
Authors: Isabelle Masouyé, Gerry Hagens, Toin H. Van Kuppevelt, Peder Madsen, Jean-Hilaire Saurat, Jacques H. Veerkamp, Michael S. Pepper, Georges Siegenthaler
Journal: Circulation Research (1997)

Abstract Epidermal fatty acid–binding protein (E-FABP), previously characterized in human keratinocytes, is a cytoplasmic protein of 15 kD that specifically binds fatty acids (FAs). Previous PAGE-immunoblotting studies indicated that several human tissues display an immunoreactive band with an electrophoretic mobility identical to that of E-FABP. The aim of this study was to determine in which cells, other than keratinocytes, E-FABP might be expressed. By immunohistochemistry, we show that E-FABP is expressed in endothelial cells of the microvasculature of the placenta, heart, skeletal muscle, small intestine, lung, and renal medulla. Interestingly, in lung, a tissue of endodermal origin, E-FABP staining was also localized to secretory cells, ie, Clara cells, goblet cells, and probably a subpopulation of pneumocytes. RNA isolated from cultured human umbilical vein and normal human dermal microvascular endothelial cells was analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR). Southern blotting and sequencing of the cloned RT-PCR products demonstrate that endothelial E-FABP is identical to keratinocyte E-FABP. These data suggest that E-FABP–mediated FA transport occurs at the level of the microvasculature in several FA target organs.
Effect of calcium, magnesium and sodium ions on in vitro nucleation of human gall bladder bile.
Authors: W D Neithercut
Journal: Gut (1989)

The effect of increasing the calcium, magnesium and sodium concentration in gall bladder bile samples from 21 patients with gall stones and nine controls on the in vitro rate of formation of cholesterol microcrystals and numbers of cholesterol microcrystals formed was examined. Addition of these cations to raise the mean maximum concentration of calcium ions to 19.8 mmol/l, of magnesium ions to 20 mmol/l and sodium ions to 998 mmol/l did not trigger nucleation in control bile samples or samples from patients with gall stones. Increasing the mean concentration of calcium ions to 8.6 mmol/l and of sodium to 320 mmol/l increased the numbers of cholesterol monohydrate crystals/0.1 mm3 counted by light polarisation phase contrast microscopy at the time of nucleation in samples from patients with gall stones from a median of 2 (range 1-10) in control portions to 18 (range 2-128) for calcium ions and 10 (range 2-141) for sodium ions (p less than 0.001). Calcium and magnesium ions were more effective than sodium ions, and calcium ions could increase crystal numbers at concentrations found in samples from patients with gall stones, median 4.6 mmol/l (range 2.7-16.9 mmol/l). The concentrations of calcium and magnesium present in bile may therefore influence the rate of development of gall stones.
Sexual Orientation in a U.S. National Sample of Twin and Nontwin Sibling Pairs
Authors: Kenneth S. Kendler, Laura M. Thornton, Stephen E. Gilman, Ronald C. Kessler
Journal: American Journal of Psychiatry (2000)

Although previous studies have suggested that sexual orientation is influenced by familial factors, which may be partly genetic, these studies have relied on unrepresentative and potentially biased samples. The authors attempted to estimate the role of genetic and environmental factors in the determination of sexual orientation in a more representative sample.Sexual orientation was assessed by a single item on a self-report questionnaire in a U.S. national sample of twin and nontwin sibling pairs. Sexual orientation was classified as heterosexual or nonheterosexual (bisexual or homosexual). The authors compared the similarity of sexual orientation in the monozygotic twins to the similarity in the same-sex dizygotic twins, all dizygotic twins, the same-sex dizygotic twins and sibling pairs, and all dizygotic twins and sibling pairs. Biometrical twin analyses were performed.All analyses demonstrated familial resemblance for sexual orientation. Resemblance was greater in the monozygotic twins than in the dizygotic twins or in the dizygotic twins plus nontwin siblings. Biometrical twin modeling suggested that sexual orientation was substantially influenced by genetic factors, but family environment may also play a role. No evidence was found for a violation of the equal-environment assumption regarding monozygotic and dizygotic twin pairs.Familial factors, which are at least partly genetic, influence sexual orientation. The results of these analyses should be interpreted in the context of low statistical power and the use of a single item to assess the complex phenotype of sexual orientation.
M2 Kupffer cells promote M1 Kupffer cell apoptosis: A protective mechanism against alcoholic and nonalcoholic fatty liver disease
Authors: Jinghong Wan, Merieme Benkdane, Fatima Teixeira-Clerc, Stéphanie Bonnafous, Alexandre Louvet, Fouad Lafdil, Françoise Pecker, Albert Tran, Philippe Gual, Ariane Mallat, Sophie Lotersztajn, Catherine Pavoine
Journal: Hepatology (2013)

Alcoholic and nonalcoholic fatty liver disease (ALD and NAFLD) are the predominant causes of liver-related mortality in Western countries. We have shown that limiting classical (M1) Kupffer cell (KC) polarization reduces alcohol-induced liver injury. Herein, we investigated whether favoring alternatively activated M2 KCs may protect against ALD and NAFLD. Ongoing alcohol drinkers and morbidly obese patients, with minimal hepatic injury and steatosis, displayed higher hepatic expression of M2 genes, as compared to patients with more severe liver lesions; individuals with limited liver lesions showed negligible hepatocyte apoptosis but significant macrophage apoptosis. Experiments in mouse models of ALD or NAFLD further showed that BALB/c or resveratrol-treated mice fed alcohol or a high-fat diet displayed preponderant M2 KC polarization, M1 KC apoptosis, and resistance to hepatocyte steatosis and apoptosis, as compared to control C57BL6/J mice. In vitro experiments in isolated KC, peritoneal, and Raw264.7 macrophages demonstrated that M1 macrophage apoptosis was promoted by conditioned medium from macrophages polarized into an M2 phenotype by either interleukin (IL)4, resveratrol, or adiponectin. Mechanistically, IL10 released from M2 cells promoted M1 death, and anti-IL10 antibodies blunted the proapoptic effects of M2-conditioned media. IL10 secreted by M2 KCs promoted selective M1 death by a mechanism involving activation of arginase in high inducible nitric oxide synthase-expressing M1 KCs. In alcohol-exposed mice, neutralization of IL10 impaired M1 apoptosis.These data uncover a novel mechanism regulating the M1/M2 balance that relies on apoptotic effects of M2 KCs towards their M1 counterparts. They suggest that promoting M2-induced M1 KC apoptosis might prove a relevant strategy to limit alcohol- and high fat-induced inflammation and hepatocyte injury.