tbuckley/cabot-search huggingface dataset:
Interspecific Divergence of Transcription Networks along Lines of Genetic Variance in Drosophila: Dimensionality, Evolvability, and Constraint
Authors: Paolo Innocenti, Stephen F. Chenoweth
Journal: Molecular Biology and Evolution (2013)

Change in gene expression is a major facilitator of phenotypic evolution. Understanding the evolutionary potential of gene expression requires taking into account complex systems of regulatory networks, the structure of which could potentially bias evolutionary trajectories. We analyzed the evolutionary potential and divergence of multigene expression in three well-characterized signaling pathways in Drosophila, the mitogen-activated protein kinase (MapK), the Toll, and the insulin receptor/Foxo (InR/Foxo or InR/TOR) pathways in a multivariate quantitative genetic framework. Gene expression data from a natural population of D. melanogaster were used to estimate the genetic variance–covariance matrices (G) for each network. Although most genes within each pathway exhibited significant genetic variance, the number of independent dimensions of multivariate genetic variance was fewer than the number of genes analyzed. However, for expression, the reduction in dimensionality was not as large as seen for other trait types such as morphology. We then tested whether gene expression divergence between D. melanogaster and an additional six species of the Drosophila genus was biased along the major axes of standing variation observed in D. melanogaster. In many cases, divergence was restricted to directions of phenotypic space harboring above average levels of genetic variance in D. melanogaster, indicating that genetic covariances between genes within pathways have biased interspecific divergence. We tested whether co-expression of genes in both sexes has also biased the pattern of divergence. Including cross-sex genetic covariances increased the degree to which divergence was biased along major axes of genetic variance, suggesting that the co-expression of genes in males and females can generate further constraints on divergence across the Drosophila phylogeny. In contrast to patterns seen for morphological traits in vertebrates, transcriptional constraints do not appear to break down as divergence time between species increases, instead they persist over tens of millions of years of divergence.
L-Asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature
Authors: A. Jaccard, B. Petit, S. Girault, F. Suarez, R. Gressin, J.-M. Zini, V. Coiteux, C. Larroche, A. Devidas, C. Thiéblemont, P. Gaulard, B. Marin, N. Gachard, D. Bordessoule, O. Hermine
Journal: Annals of Oncology (2008)
Accumulation of natural killer and cytotoxic T large granular lymphocytes in the liver during virus infection.
Authors: K W McIntyre, R M Welsh
Journal: The Journal of Experimental Medicine (1986)

The immunologic mechanisms involved in virus-induced hepatitis were examined by measuring the cytotoxic capabilities and the morphologic and antigenic phenotypes of leukocytes isolated from livers of virus-infected mice. Large granular lymphocytes (LGL) of both natural killer (NK) cell and cytotoxic T lymphocyte (CTL) phenotypes were found to accumulate in livers of mice infected with either the nonhepatotropic Armstrong strain of lymphocytic choriomeningitis virus (LCMV-ARM) or the hepatotropic WE strain (LCMV-WE). Between days 1 and 5 postinfection (p.i.), both viruses induced a three- to fourfold increase in NK cell lytic activity in the livers of C3H/St mice and a three- to fourfold increase in the number of LGL in the organ. These LGL were characterized as NK cells on the basis of cell surface antigens, kinetics of appearance, target cell range, and morphology. By day 7 p.i., virus-specific, H-2-restricted, Thy-1+, Lyt-2+, CTL activity was present in the liver, and its appearance correlated with a second wave of LGL accumulation. CTL activity, total leukocyte number, and CTL/LGL number were at least fivefold higher in the livers of mice infected with LCMV-WE than with LCMV-ARM. The dramatic LCMV-WE-induced day 7 increases in total leukocytes and LGL were absent in athymic nude (nu/nu) mice, suggesting that the increases were T cell-dependent. LCMV-ARM infection of C57BL/6 mice induced significant spleen CTL activity but little liver CTL activity, whereas LCMV-WE infection resulted in significant liver CTL activity but minimal spleen CTL activity. Mice infected with the cytopathic hepatotropic viruses, mouse hepatitis virus (MHV) and murine cytomegalovirus (MCMV), experienced much greater increases in liver NK/LGL by day 3 p.i. than did mice infected with LCMV or injected with the interferon-inducer poly(I-C). MHV-infected mice homozygous for the beige (bg/bg) mutation also exhibited significant increases in liver NK/LGL cell number and activity, although the activity was less than heterozygote controls, and the morphology of the LGL granules was aberrant. These data show that the LGL accumulate in virus-infected organs, in this case, the liver. An early NK/LGL influx is most pronounced during infection with cytopathic hepatotropic viruses. This initial influx of NK/LGL is followed later by an influx of CTL also possessing LGL morphology. The CTL/LGL response in the liver is significantly greater during hepatotropic virus infections, even when a strong CTL response in the spleen is lacking.
Phase I Trial of Adoptive Cell Transfer with Mixed-Profile Type-I/Type-II Allogeneic T Cells for Metastatic Breast Cancer
Authors: Nancy M. Hardy, Miriam E. Mossoba, Seth M. Steinberg, Vicki Fellowes, Xiao-Yi Yan, Frances T. Hakim, Rebecca R. Babb, Daniele Avila, Juan Gea-Banacloche, Claude Sportès, Bruce L. Levine, Carl H. June, Hahn M. Khuu, Ashley E. Carpenter, Michael C. Krumlauf, Andrew J. Dwyer, Ronald E. Gress, Daniel H. Fowler, Michael R. Bishop
Journal: Clinical Cancer Research (2011)

Metastatic breast cancer (MBC) response to allogeneic lymphocytes requires donor T-cell engraftment and is limited by graft-versus-host disease (GVHD). In mice, type-II-polarized T cells promote engraftment and modulate GVHD, whereas type-I-polarized T cells mediate more potent graft-versus-tumor (GVT) effects. This phase I translational study evaluated adoptive transfer of ex vivo costimulated type-I/type-II (T1/T2) donor T cells with T-cell-depleted (TCD) allogeneic stem cell transplantation (AlloSCT) for MBC.
Spontaneous heart rate, propranolol, and ischaemia-induced ventricular fibrillation in the dog
Authors: R. D. REYNOLDS, S. V. CALZADILLA, R. J. LEE
Journal: Cardiovascular Research (1978)

Abrupt coronary occlusion was performed in anaesthetised, open-chest dogs with pre-occlusion arterial blood PO2 ranging from 8.0 to 10.7 kPa (60 to mmHg). Ventricular fibrillation occurred in 15/19 dogs with high spontaneous heart rate (less than 155 beats.min-1) and in 0/8 dogs with low spontaneous heart rate (less than 155 beats.min-1). Dogs with low spontaneous heart rate fibrillated when paced at a fast rate (200.min-1) (4/5). In dogs with high spontaneous heart rate fibrillation occurred in 0/5 dogs when propranolol reduced spontaneous heart rate, but in 3/5 dogs when reduction in spontaneous heart rate in response to propranolol was prevented by pacing.
Conformational templating of α-synuclein aggregates in neuronal-glial cultures
Authors: Amanda N Sacino, Michael A Thomas, Carolina Ceballos-Diaz, Pedro E Cruz, Awilda M Rosario, Jada Lewis, Benoit I Giasson, Todd E Golde
Journal: Molecular Neurodegeneration (2013)

Genetic studies have established a causative role for α-synuclein (αS) in Parkinson's disease (PD), and the presence of αS aggregates in the form of Lewy body (LB) and Lewy neurite (LN) protein inclusions are defining pathological features of PD. Recent data has established that extracellular αS aggregates can induce intracellular αS pathologies supporting the hypothesis that αS pathology can spread via a "prion-like" self-templating mechanism.Here we investigated the potential for conformational templating of αS intracellular aggregates by seeding using recombinant wild-type and PD-linked mutant (A53T and E46K) αS in primary mixed neuronal-glial cultures. We find that wild-type and A53T αS fibrils predominantly seed flame-like inclusions in both neurons and astrocytes of mixed primary cultures; whereas the structurally distinct E46K fibrils seed punctate, rounded inclusions. Notably, these differences in seeded inclusion formation in these cultures reflect differences in inclusion pathology seen in transgenic mice expressing the A53T or E46K αS mutants. We further show that the inclusion morphology is dictated primarily by the seed applied rather than the form of αS expressed. We also provide initial evidence that αS inclusion pathology can be passaged in primary astrocyte cultures.These studies establish for the first time that αS aggregation in cultured cells can occur by a morphological self-templating mechanism.
A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33
Authors: Gloria M Petersen, Laufey Amundadottir, Charles S Fuchs, Peter Kraft, Rachael Z Stolzenberg-Solomon, Kevin B Jacobs, Alan A Arslan, H Bas Bueno-de-Mesquita, Steven Gallinger, Myron Gross, Kathy Helzlsouer, Elizabeth A Holly, Eric J Jacobs, Alison P Klein, Andrea LaCroix, Donghui Li, Margaret T Mandelson, Sara H Olson, Harvey A Risch, Wei Zheng, Demetrius Albanes, William R Bamlet, Christine D Berg, Marie-Christine Boutron-Ruault, Julie E Buring, Paige M Bracci, Federico Canzian, Sandra Clipp, Michelle Cotterchio, Mariza de Andrade, Eric J Duell, J Michael Gaziano, Edward L Giovannucci, Michael Goggins, Göran Hallmans, Susan E Hankinson, Manal Hassan, Barbara Howard, David J Hunter, Amy Hutchinson, Mazda Jenab, Rudolf Kaaks, Charles Kooperberg, Vittorio Krogh, Robert C Kurtz, Shannon M Lynch, Robert R McWilliams, Julie B Mendelsohn, Dominique S Michaud, Hemang Parikh, Alpa V Patel, Petra H M Peeters, Aleksandar Rajkovic, Elio Riboli, Laudina Rodriguez, Daniela Seminara, Xiao-Ou Shu, Gilles Thomas, Anne Tjønneland, Geoffrey S Tobias, Dimitrios Trichopoulos, Stephen K Van Den Eeden, Jarmo Virtamo, Jean Wactawski-Wende, Zhaoming Wang, Brian M Wolpin, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Joseph F Fraumeni, Robert N Hoover, Patricia Hartge, Stephen J Chanock
Journal: Nature Genetics (2010)
Recommended Guidelines for Uniform Reporting of Data From Drowning
Authors: A.H. Idris, R.A. Berg, J. Bierens, L. Bossaert, C.M. Branche, A. Gabrielli, S.A. Graves, A.J. Handley, R. Hoelle, P.T. Morley, L. Papa, P.E. Pepe, L. Quan, D. Szpilman, J.G. Wigginton, J.H. Modell, D. Atkins, M. Gay, W. Kloeck, S. Timerman
Journal: Circulation (2003)

HomeCirculationVol. 108, No. 20Recommended Guidelines for Uniform Reporting of Data From Drowning
Combined use of positron emission tomography and volume doubling time in lung cancer screening with low-dose CT scanning
Authors: H. Ashraf, A. Dirksen, A. Loft, A. K. Bertelsen, K. S. Bach, H. Hansen, J. H. Pedersen, J. Mortensen
Journal: Thorax (2010)

<h3>BACKGROUND:</h3> Patients receiving in-centre hemodialysis are at high risk of exposure to SARS-CoV-2 and death if infected. One dose of the BNT162b2 SARS-CoV-2 vaccine is efficacious in the general population, but responses in patients receiving hemodialysis are uncertain. <h3>METHODS:</h3> We obtained serial plasma from patients receiving hemodialysis and health care worker controls before and after vaccination with 1 dose of the BNT162b2 mRNA vaccine, as well as convalescent plasma from patients receiving hemodialysis who survived COVID-19. We measured anti–receptor binding domain (RBD) immunoglobulin G (IgG) levels and stratified groups by evidence of previous SARS-CoV-2 infection. <h3>RESULTS:</h3> Our study included 154 patients receiving hemodialysis (135 without and 19 with previous SARS-CoV-2 infection), 40 controls (20 without and 20 with previous SARS-CoV-2 infection) and convalescent plasma from 16 patients. Among those without previous SARS-CoV-2 infection, anti-RBD IgG was undetectable at 4 weeks in 75 of 131 (57%, 95% confidence interval [CI] 47% to 65%) patients receiving hemodialysis, compared with 1 of 20 (5%, 95% CI 1% to 23%) controls (<i>p</i> &lt; 0.001). No patient with nondetectable levels at 4 weeks developed anti-RBD IgG by 8 weeks. Results were similar in non-immunosuppressed and younger individuals. Three patients receiving hemodialysis developed severe COVID-19 after vaccination. Among those with previous SARS-CoV-2 infection, median anti-RBD IgG levels at 8 weeks in patients receiving hemodialysis were similar to controls at 3 weeks (<i>p</i> = 0.3) and to convalescent plasma (<i>p</i> = 0.8). <h3>INTERPRETATION:</h3> A single dose of BNT162b2 vaccine failed to elicit a humoral immune response in most patients receiving hemodialysis without previous SARS-CoV-2 infection, even after prolonged observation. In those with previous SARS-CoV-2 infection, the antibody response was delayed. We advise that patients receiving hemodialysis be prioritized for a second BNT162b2 dose at the recommended 3-week interval.
A Randomized, Controlled Trial of Combination Therapy for Chronic Hepatitis B: Comparing Pegylated Interferon-α2b and Lamivudine with Lamivudine Alone
Authors: Henry Lik-Yuen Chan, Nancy Wai-Yee Leung, Alex Yui Hui, Vincent Wai-Sun Wong, Choong-Tsek Liew, Angel Mei-Ling Chim, Francis Ka-Leung Chan, Lawrence Cheung-Tsui Hung, Yuk-Tong Lee, John Siu-Lun Tam, Christopher Wai-Kei Lam, Joseph Jao-Yiu Sung
Journal: Annals of Internal Medicine (2005)

Background: Conventional interferon and lamivudine monotherapy are unsatisfactory in treating hepatitis B virus (HBV) infection. Objective: To evaluate the efficacy and safety of pegylatedinterferon-α2b and lamivudine combination therapy for chronic hepatitis B. Design: Randomized, controlled, open-label trial. Setting: Outpatient clinic in a referral center. Participants: 100 treatment-naive patients with hepatitis B e antigen (HBeAg)–positive chronic hepatitis B and moderately elevated alanine aminotransferase levels. Measurement: The primary end point was sustained virologic response (HBeAg seroconversion and HBV DNA level < 500 000 copies/mL) at 24 weeks after cessation of treatment. Intervention: A staggered regimen of combination therapy with pegylated interferon-α2b (1.5 µg/kg of body weight per week; maximum, 100 µg) given for 32 weeks plus lamivudine (100 mg daily) given for 52 weeks versus lamivudine (100 mg daily) monotherapy given for 52 weeks. Of the 100 participants, 96% completed treatment and 80% completed post-treatment follow-up. Results: The rate of sustained virologic response was 36% for the combination treatment group and 14% for the lamivudine monotherapy group (absolute difference, 22 percentage points [95% CI, 6 to 38 percentage points]). End-of-treatment outcomes showed that, compared with monotherapy, patients receiving combination therapy more often had virologic response (60% vs. 28% [absolute difference, 32 percentage points (CI, 14 to 50 percentage points)]); had more substantial reductions of HBV DNA (3.91 log10 copies/mL vs. 2.83 log10 copies/mL); and less often had lamivudine-resistant mutants (21% vs. 40%). The percentages of patients with normalization of alanine aminotransferase levels and histologic improvement did not differ. Adverse effects, such as transient influenza-like symptoms, alopecia, and local erythematous reactions, were more common with combination therapy. Limitations: This study lacked a double-blind design and was conducted at 1 institution. Because of the staggered pegylated interferon–lamivudine regimen, patients assigned to combination therapy received treatment for 8 weeks longer than those assigned to monotherapy. Conclusions: In patients with HBeAg-positive chronic hepatitis B, staggered combination treatment with pegylated interferon-α2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy.
Covariance between Testes Size and Substitution Rates in Primates
Authors: Alex Wong
Journal: Molecular Biology and Evolution (2014)

Understanding the causes of substitution rate variation is an important goal in the study of molecular evolution. It has been proposed that sperm competition intensity may affect genome-wide rates of substitution as a by-product of selection on sperm numbers. Here, I test this hypothesis by applying recently developed Bayesian methods to a data set consisting of approximately 35 kb of sequence data from 55 primate species. I find evidence for positive covariance between testes mass and the rate of substitution, independently of the potentially confounding effects of body mass and longevity.
Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma☆☆☆
Authors: Makoto Hoshino, Miki Takahashi, Yujiro Takai, JaeJoon Sim
Journal: Journal of Allergy and Clinical Immunology (1999)
The role of semantic association and emotional contagion for the induction of emotion with music
Authors: Thomas Fritz, Stefan Koelsch
Journal: Behavioral and Brain Sciences (2008)

Abstract We suggest that semantic association may be a further mechanism by which music may elicit emotion. Furthermore, we note that emotional contagion is not always an immediate process requiring little prior information processing; rather, emotional contagion contributing to music processing may constitute a more complex decoding mechanism for information inherent in the music, which may be subject to a time course of activation.
Heterogeneity of hemoglobin gamma chains in normal newborns and in cases of alpha and beta thalassemia
Authors: Luan Eng Lie‐Injo, Z. I. Randhawa, J. P. Kane, J. Ganesan, R. George
Journal: American Journal of Hematology (1979)

Abstract The ratio of Gγ to Aγ chains was studied in 13 normal healthy newborns and in eight neonates with hydrops fetalis due to homozygous α‐thalassemia. The findings in the normal healthy newborns agreed with those of earlier reports. In homozygous α‐thalassemia the Gγ and Aγ ratio appeared generally lower than in healthy control newborns, but one of the hydrops fetalis cases had a very high Gγ value. In all 13 normal healthy newborns, in 8 patients with homozygous α‐thalassemia, and in 4 patients with homozygous β‐thalassemia, Tγ chains with threonine at position 75 were detected in addition to Iγ chains with isoleucine at position 75. In homozygous α‐thalassemia, the Tγ‐to‐Iγ ratio seemed lower and in homozygous β‐thalassemia higher than in normal newborns.
Molecular and Biochemical Analyses of Platelet-Derived Growth Factor Receptor (PDGFR) B, PDGFRA, and KIT Receptors in Chordomas
Authors: Elena Tamborini, Francesca Miselli, Tiziana Negri, M. Stefania Lagonigro, Samantha Staurengo, Gian Paolo Dagrada, Silvia Stacchiotti, Elisa Pastore, Alessandro Gronchi, Federica Perrone, Antonino Carbone, Marco A. Pierotti, Paolo G. Casali, Silvana Pilotti
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We have previously shown the presence of an activated platelet-derived growth factor (PDGF) receptor (PDGFR) B and its ligand PDGFB in a limited number of patients with clinical and radiological responses to imatinib mesylate treatment. This article describes the results of comprehensive molecular/biochemical analyses of the three receptors targeted by the drug (PDGFRB, PDGFRA, and KIT) in a series of 31 chordoma patients. Experimental Design: The presence and activation status of PDGFRB, PDGFRA, and KIT receptors were investigated by means of immunoprecipitation and Western blot analyses complemented by immunohistochemistry, their expression level was analyzed by means of real-time PCR, and the occurrence of activating point mutations was investigated by means of cDNA sequencing. The PDGFB, PDGFA, and stem cell factor cognate ligands were investigated by reverse transcription-PCR, and gene status was assessed by fluorescence in situ hybridization. Results: The results show that PDGFRB was highly expressed and phosphorylated, whereas PDGFRA and KIT were less expressed but phosphorylated and thus activated. These findings, together with the absence of gain-of-function mutations and the presence of the cognate ligands, strongly support the hypothesis that the activation mechanism is the autocrine/paracrine loop. No role seems to be played by gene amplification. Conclusions: In the light of our findings, the clinical benefit observed in chordoma patients treated with imatinib seems to be attributable to the switching off of all three receptors.
Role of the sarcolemma in triggered propagated contractions in rat cardiac trabeculae.
Authors: M C Daniels, D Fedida, C Lamont, H E ter Keurs
Journal: Circulation Research (1991)

We have recently described that after contractions propagate through multicellular cardiac muscle preparations. These propagating contractions are triggered in damaged regions of rat right ventricular trabeculae during relaxation of electrically stimulated twitches. Propagation of triggered contractions has been attributed to calcium ions that diffuse along the preparation, causing calcium-induced calcium release from the sarcoplasmic reticulum in adjacent cells. In the present study we have investigated a possible role of the sarcolemma and delayed afterdepolarizations (DADs) in the initiation and propagation of triggered propagated contractions (TPCs) in multicellular preparations. We studied whether 1) TPCs are accompanied by delayed sarcolemmal depolarizations, 2) such depolarizations mediate local contraction, and 3) an intact sarcolemma is required for propagation of contractions. TPCs that remained stable for prolonged periods of time could be induced by trains of 15 stimuli (2 Hz, 15-second intervals) at lowered temperature (19-21 degrees C) of the superfusing Krebs-Henseleit medium and a [Ca(2+)]o of 1.0-1.5 mM. Although TPCs could be induced at 38 degrees C and a [Ca2+]o of 3.0-4.0 mM, they disappeared within 10 minutes. Force was measured with a silicon strain gauge; length and shortening of sarcomeres were measured at two sites of the muscle using laser diffraction techniques. Membrane potential was measured with flexible microelectrodes. Saponin was used to selectively render the sarcolemma permeable to small ions and molecules. Propagation velocity of TPCs in intact trabeculae varied from 1.7 to 13.4 mm/sec at 19-21 degrees C. TPCs were accompanied by DADs that could reach threshold and induce triggered arrhythmias. Changes in latency, duration, and force of TPCs, induced by changing [Ca(2+)]o or the number of conditioning stimuli, were closely matched by changes in latency, duration, and amplitude of DADs; DADs consistently preceded TPCs, on average by 60 msec. Local heating of the muscle, by applying a current through an insulated platinum wire (diameter 100 microns) that touched the muscle, interrupted propagation of TPCs reversibly. DADs were, in the absence of a local contraction, still recorded distal to the heated site. In muscles that were treated with saponin and exposed to solutions approximating the intracellular milieu, spontaneously occurring local contractions that propagated in both directions (at velocities of 70-200 microns/sec) were elicited at a bathing calcium concentration of approximately 0.6 microM. Below this threshold, propagated contractions could be triggered by pressure ejection of a calcium-containing solution from a microelectrode positioned close to the trabecula.(ABSTRACT TRUNCATED AT 400 WORDS)
TCT-59 Effect of Intracoronary Abciximab and Aspiration Thrombectomy on Microvascular Obstruction in Large Anterior Myocardial Infarction: The INFUSE-AMI MRI Substudy
Authors: Akiko Maehara, Gary Mintz, Sorin Brener, Jan-Henk Dambrink, Magdi El-Omar, Anthony Gershlick, Martin Fahy, Roxana Mehran, C. Michael Gibson, Gregg Stone
Journal: Journal of the American College of Cardiology (2012)