tbuckley/cabot-search huggingface dataset:
Impact of the Excision of an Ancient Repeat Insertion on Rickettsia conorii Guanylate Kinase Activity
Authors: Chantal Abergel, Guillaume Blanc, Vincent Monchois, Patricia Renesto, Cécile Sigoillot, Hiroyuki Ogata, Didier Raoult, Jean-Michel Claverie
Journal: Molecular Biology and Evolution (2006)

The genomic sequencing of Rickettsia conorii revealed a new family of Rickettsia-specific palindromic elements (RPEs) capable of in-frame insertion in preexisting open reading frames (ORFs). Many of these altered ORFs correspond to proteins with well-characterized or essential functions in other microorganisms. Previous experiments indicated that RPE-containing genes are normally transcribed and that no excision of the repeat occurs at the mRNA level. Using mass spectrometry, we now confirmed the retention of the RPE-derived amino acid residues in 4 proteins successfully expressed in Escherichia coli, raising the general question of the consequences of this common insertion event on the fitness of Rickettsia enzymes. The predicted guanylate kinase activity of the R. conorii gmk gene product was measured both on the RPE-containing and RPE-excised recombinant proteins. We show that the 2 proteins are active but exhibit substantial differences in their affinity for adenosine triphosphate, guanosine monophosphate, and catalytic constants. The distribution of the RPEgmk insert among Rickettsia species indicates that the insertion event is ancient and occurred after the divergence of Rickettsia felis and R. conorii but before that of Rickettsia helvetica and R. conorii. We found no evidence that the gmk gene fixed adaptive changes to compensate the RPE peptide insertion. Furthermore, the analysis of the rates of divergence in 23 RPE-containing genes indicates that coding RPE repeats tend to evolve under weak selective constraint, at a rate similar to intergenic noncoding RPE sequences. Altogether, these results suggest that the insertion of RPE-encoded “selfish peptides,” although respecting the original fold and activity of the host proteins, might be slightly detrimental to the enzyme efficiency within limits tolerable for slow-growing intracellular parasites such as Rickettsia.
Neural Basis of the Perception and Estimation of Time
Authors: Hugo Merchant, Deborah L. Harrington, Warren H. Meck
Journal: Annual Review of Neuroscience (2013)

Understanding how sensory and motor processes are temporally integrated to control behavior in the hundredths of milliseconds-to-minutes range is a fascinating problem given that the basic electrophysiological properties of neurons operate on a millisecond timescale. Single-unit recording studies in monkeys have identified localized timing circuits, whereas neuropsychological studies of humans who have damage to the basal ganglia have indicated that core structures, such as the cortico-thalamic-basal ganglia circuit, play an important role in timing and time perception. Taken together, these data suggest that a core timing mechanism interacts with context-dependent areas. This idea of a temporal hub with a distributed network is used to investigate the abstract properties of interval tuning as well as temporal illusions and intersensory timing. We conclude by proposing that the interconnections built into this core timing mechanism are designed to provide a form of degeneracy as protection against injury, disease, or age-related decline.
Longitudinal Tracking of Left Ventricular Mass Over the Adult Life Course
Authors: Wolfgang Lieb, Vanessa Xanthakis, Lisa M. Sullivan, Jayashri Aragam, Michael J. Pencina, Martin G. Larson, Emelia J. Benjamin, Ramachandran S. Vasan
Journal: Circulation (2009)

Information is limited on the longitudinal tracking of left ventricular (LV) mass over the adult life course and the determinants of such change.We used multilevel modeling to evaluate the correlates of LV mass prospectively over a 16-year period in 4217 Framingham study participants (mean age 45 years, 53% women) using up to 4 serial routine echocardiographic observations on each individual (11 762 observations). Age, sex, body mass index, systolic blood pressure, antihypertensive treatment, smoking, and diabetes mellitus were related to longitudinal measures of LV mass. Women and participants with diabetes mellitus experienced a steeper increase in LV mass with advancing age (compared with men and those without diabetes mellitus; P for interactions <0.0001 and 0.0003, respectively). Women also displayed greater increments in LV mass with increasing body mass index (compared with men, P=0.04 for interaction). Participants with optimal values of these risk factors experienced lesser increases in LV mass over time. Analyses evaluating short-term (4-year) changes in LV mass (2605 unique individuals providing 4494 observations) identified the same key determinants that influenced its long-term trajectory (ie, body mass index, sex, systolic blood pressure, antihypertensive treatment, and smoking).Our longitudinal observations on a large community-based sample identified higher blood pressure, excess adiposity, smoking, and diabetes mellitus as fundamental determinants of LV mass tracking over the adult life course. These observations are consistent with the notion that maintenance of optimal levels of these risk factors in midlife will reduce the burden of LV hypertrophy, and possibly heart failure, in older age.
Serum transferrin receptor in hereditary hemochromatosis and African siderosis
Authors: Roy D. Baynes, James D. Cook, Thomas H. Bothwell, Brian M. Friedman, Theo E. Meyer
Journal: American Journal of Hematology (1994)

Abstract The present investigation evaluated the serum transferrin receptor concentration in subjects with nontransfusional iron overload who were identified in two separate studies on the basis of a serum ferritin level above 400 μg/L. Subjects with preciinical hereditary hemochromatosis were evaluated in the first study and those with the African form of iron overload in the second. in the first study, hereditary hemochromatosis was identified in 14 white men on the basis of a persistent elevation in transferrin saturation above 55%. The serum receptor concentration was elevated above the upper cut‐off of 8.5 mg/L in two of the subjects, but the mean receptor of 6.1 ± 1.4 mg/L (mean ± 2 SE) did not differ significantly from the normal mean for this assay of 5.6 ± 0.3 mg/L. In the same study, 60 control subjects with secondary iron overload were identified on the basis of a serum ferritin persistently above 400 μg/L, with a normal serum C‐reactive protein concentration but with a transferrin saturation &lt;55%. Three of these subjects had an elevated serum receptor concentration but the mean value of 5.5 ± 0.4 mg/L did not differ from normals nor from subjects with hemochromatosis. In the second study, 49 black Africans with iron overload were divided into those with or without an elevated transferrin saturation. The mean serum receptor concentration of 5.0 ± 0.8 mg/L and 4.5 ± 0.4 mg/L, respectively, did not differ statistically. It was concluded that there is no evidence of generalized dysreguiation of the transferrin receptor in hemochromatosis or African siderosis. © 1994 Wiley‐Liss, Inc.
The Processing of Single Words Studied with Positron Emission Tomography
Authors: S E Petersen, J A Fiez
Journal: Annual Review of Neuroscience (1993)

Language, the most profoundly human of all abilities, has been a focus of study in many disciplines. Cognitive psychological studies of normals have been used to describe language-related information processing. The correlation of language-related behavioral deficits with the site of nervous system injury has been used to relate language processing to brain function. Over the past decade, there has been an explosion in the use of imaging technology, including positron emission tomography (PET), to study the structure and function of the human brain. This article explores how functional imaging with PET has been applied to the study of language, particularly the study of the processing of single words (lexical processing). To understand how PET is used in the study of lexical processing, one has to have some understanding of the technology of PET, a framework in which to explore the processing of words, and knowledge of the ques­ tions that can be addressed by the specific application of PET studies to issues in lexical processing. This paper follows that path with a brief general introduction to PET, an outline of some aspects of lexical processing, and a presentation of selected PET studies that have addressed issues in lexical processing.
Epstein-Barr virus transformation of human pre-B cells.
Authors: M Hansson, K Falk, I Ernberg
Journal: The Journal of Experimental Medicine (1983)

In vitro infection of human B lymphocytes with Epstein-Barr virus (EBV) results in establishment of B lymphoblastoid cell lines that reflect normal B cell phenotypes. In this study we have investigated whether immature B cells from fetal bone marrow and liver can serve as targets for EBV. The fetal bone marrow cells were readily transformed by EBV. Among the resulting cell lines, five were surface Ig (sIg)-negative. Three B cell-associated antigens defined by monoclonal antibodies were expressed to the same extent on the fetal cell lines, whether they belonged to the sIg- or sIg+ group. The various differentiation stages that these cell lines may represent are discussed.
<scp>l</scp> -Arginine and <i>S</i> -Nitrosoglutathione Reduce Embolization in Humans
Authors: Zoltan Kaposzta, Paul A. Baskerville, David Madge, Simon Fraser, John F. Martin, Hugh S. Markus
Journal: Circulation (2001)

Background — l -Arginine reduces platelet aggregation and adhesion in ex vivo studies, but there is no evidence as yet that it has a therapeutic effect on clinical end points. Doppler ultrasound can detect cerebral emboli noninvasively. Such embolic signals are common after carotid endarterectomy, and their frequency predicts risk of stroke recurrence. We used this situation to determine the antiplatelet efficacy of l -arginine and S -nitrosoglutathione (GSNO), a physiological nitric oxide donor with possible platelet specificity. Methods and Results —Patients undergoing carotid endarterectomy were randomized in a double-blind manner between l -arginine (n=14), GSNO (n=14), or placebo (n=14) administered intravenously for 90 minutes, starting 30 minutes after skin closure. All patients were pretreated with aspirin and given heparin during surgery. Transcranial Doppler recordings were made from the ipsilateral middle cerebral artery for 4 hours after surgery, beginning 30 minutes after skin closure, and also at 6 and 24 hours. There were highly significant reductions in the number of Doppler embolic signals in the l -arginine and GSNO groups; first 4 hours, median (range) number of embolic signals, placebo 44.7 (6 to 778), l -arginine 9.5 (0 to 225), and GSNO 0.8 (0 to 8), both P &lt;0.001 versus control values. The reduction in the signals persisted at the 24-hour recording. Conclusions —Intravenous l -arginine and GSNO attenuate Doppler embolic signals in humans. Modulation of the NO system with these agents may have applications in the treatment of thromboembolic disease. This study demonstrates the potential application of ultrasonic embolic signal detection to examine the efficacy of new antiplatelet agents in relatively small numbers of patients.
662 OUTCOME OF PATIENTS WITH HEPATOCELLULAR CARCINOMA LISTED FOR LIVER TRANSPLANTATION BEFORE AND AFTER THE MELD-BASED ALLOCATION SYSTEM WITHIN EUROTRANSPLANT A BELGIAN MULTICENTRE RETROSPECTIVE STUDY
Authors: B. Vos, S. Rogge, F. Nevens, J. Pirenne, J. Lerut, O. Ciccarelli, H. Van Vlierberghe, R. Troisi, C. Moreno, V. Lucidi, V. Donckier, J. Delwaide, O. Detry, P. Michielsen, T. Chapelle, M. Adler
Journal: Journal of Hepatology (2011)
Transplantation of Multiple Abdominal Viscera
Authors: Thomas E. Starzl
Journal: JAMA (1989)

Two children with the short-gut syndrome and secondary liver failure were treated with evisceration and transplantation en bloc of the stomach, small intestine, colon, pancreas, and liver. The first patient died perioperatively, but the second lived for more than 6 months before dying of an Epstein-Barr virus—associated lymphoproliferative disorder that caused biliary obstruction and lethal sepsis. There was never evidence of graft rejection or of graft-vs-host disease in the long-surviving child. The constituent organs of the homograft functioned and maintained their morphological integrity throughout the 193 days of survival. (<i>JAMA</i>. 1989;261:1449-1457)
Serendipitous discovery of Wolbachia genomes in multiple Drosophila species.
Authors: Steven L Salzberg, Julie C Dunning Hotopp, Arthur L Delcher, Mihai Pop, Douglas R Smith, Michael B Eisen, William C Nelson
Journal: Genome biology (2005)

The Trace Archive is a repository for the raw, unanalyzed data generated by large-scale genome sequencing projects. The existence of this data offers scientists the possibility of discovering additional genomic sequences beyond those originally sequenced. In particular, if the source DNA for a sequencing project came from a species that was colonized by another organism, then the project may yield substantial amounts of genomic DNA, including near-complete genomes, from the symbiotic or parasitic organism.
Stimulation of muscarinic receptors raises free intracellular Ca2+ concentration in rat ventricular myocytes.
Authors: M Korth, V K Sharma, S S Sheu
Journal: Circulation Research (1988)

The effect of carbachol on free intracellular calcium concentration, ([Ca2+]i) and on intracellular hydrogen concentration (pHi) was determined from fluorescence signals obtained from rat ventricular myocytes. Application of carbachol (300 mumol/l) to quin2-loaded myocytes bathed in 2 mmol/l Ca2+-containing solution caused [Ca2+]i to increase within 7-10 minutes from 182 +/- 9 to 212 +/- 11 nmol/l (n = 4). Carbachol acted via stimulation of muscarinic receptors because atropine (1 mumol/l) either prevented or abolished the increase in [Ca2+]i. Carbachol also produced a positive inotropic effect in rat papillary muscles contracting isometrically at a frequency of 0.5 Hz and enhanced contracture in resting preparations in the presence of high extracellular Ca2+ concentration ([Ca2+]o) (20 mmol/l). The effect of carbachol on [Ca2+]i was dependent on [Ca2+]o. In the presence of 10 mmol/l [Ca2+]o, the increase in [Ca2+]i was about two times that elicited by carbachol when bath [Ca2+]o was 2 mmol/l. Reduction of [Ca2+]o to 50 mumol/l abolished the carbachol effect but did not prevent caffeine-induced Ca2+ release. The carbachol-induced rise in [Ca2+]i remained unchanged in the presence of either 10 mmol/l caffeine or 1 mumol/l ryanodine. In the absence of extracellular Na+ concentration [( Na+]o), carbachol no longer produced an increase in [Ca2+]i of cardiomyocytes and failed to enhance Na+-withdrawal contracture of the rat papillary muscle. In contrast to the effect on [Ca2+]i, carbachol did not produce any change in pHi as determined from fluorescence signals obtained from rat ventricular myocytes loaded with 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein.(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphocyte Activation Gene-3 Fusion Protein Increases the Potency of a Granulocyte Macrophage Colony-Stimulating Factor–Secreting Tumor Cell Immunotherapy
Authors: Betty Li, Melinda VanRoey, Frederic Triebel, Karin Jooss
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The purpose of the present study was to evaluate granulocyte macrophage colony-stimulating factor (GM-CSF)-secreting tumor cell immunotherapy, which is known to stimulate a potent and long-lasting antigen-specific immune response in combination with lymphocyte activation gene-3 fusion protein (LAG-3Ig), which has been shown to act as an adjuvant for priming T helper type 1 and cytotoxic T-cell responses. Experimental Design: Survival and immune monitoring studies were done in the B16 melanoma model. GM-CSF–secreting tumor cell immunotherapy was administered as a single s.c. injection and LAG-3Ig was administered s.c. at the immunotherapy site. Results: The studies reported here show that combining LAG-3Ig with GM-CSF–secreting tumor cell immunotherapy prolonged the survival of tumor-bearing animals compared with animals treated with either therapy alone. Prolonged survival correlated with increased numbers of systemic IFNγ-secreting CD8+ T cells and a significantly increased infiltration of activated effector CD8+ T cells into the tumor. Moreover, an increase in antigen-specific IgG1 humoral responses was detected in serum of animals injected with the combination therapy compared with animals injected with either therapy alone. Conclusion: LAG-3Ig combined with a GM-CSF–secreting tumor cell immunotherapy stimulated both cellular and humoral antitumor immune responses that correlated with prolonged survival in tumor-bearing animals.
Transient reversal of bone marrow aplasia associated with lymphocyte depleted hodgkin's disease after combination chemotherapy
Authors: P. G. Johnston, F. J. Sullivan, F. W. Ruscetti, D. L. Longo, D. G. Connaghan
Journal: American Journal of Hematology (1991)

Abstract This report describes a patient with lymphocyte depleted Hodgkin's disease who presented with bone marrow aplasia. The aplastic marrow reverted to normal after initiation of MOPP chemotherapy; however, 4 months after completion of therapy, bone marrow aplasia recurred in the absence of recurrent Hodgkin's disease. The patient remains free of Hodgkin's disease 34 months after completion of chemotherapy. Bone marrow abnormalities in Hodgkin's disease are reviewed and the current understanding of the pathological mechanisms leading to aplastic anemia is discussed.
Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent (COMPARE II): a randomised, controlled, non-inferiority trial
Authors: Pieter Cornelis Smits, Sjoerd Hofma, Mario Togni, Nicolás Vázquez, Mariano Valdés, Vassilis Voudris, Ton Slagboom, Jean-Jaques Goy, Andre Vuillomenet, Antoni Serra, Ramiro Trillo Nouche, Peter den Heijer, Martin van der Ent
Journal: The Lancet (2013)
Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis
Authors: Steffen Koschmieder, Berthold Göttgens, Pu Zhang, Junko Iwasaki-Arai, Koichi Akashi, Jeffery L. Kutok, Tajhal Dayaram, Kristin Geary, Anthony R. Green, Daniel G. Tenen, Claudia S. Huettner
Journal: Blood (2004)
Enforced Granulocyte/Macrophage Colony-stimulating Factor Signals Do Not Support Lymphopoiesis, but Instruct Lymphoid to Myelomonocytic Lineage Conversion
Authors: Junko Iwasaki-Arai, Hiromi Iwasaki, Toshihiro Miyamoto, Sumiko Watanabe, Koichi Akashi
Journal: The Journal of Experimental Medicine (2003)

We evaluated the effects of ectopic granulocyte/macrophage colony-stimulating factor (GM-CSF) signals on hematopoietic commitment and differentiation. Lineage-restricted progenitors purified from mice with the ubiquitous transgenic human GM-CSF receptor (hGM-CSFR) were used for the analysis. In cultures with hGM-CSF alone, hGM-CSFR-expressing (hGM-CSFR+) granulocyte/monocyte progenitors (GMPs) and megakaryocyte/erythrocyte progenitors (MEPs) exclusively gave rise to granulocyte/monocyte (GM) and megakaryocyte/erythroid (MegE) colonies, respectively, providing formal proof that GM-CSF signals support the GM and MegE lineage differentiation without affecting the physiological myeloid fate. hGM-CSFR transgenic mice were crossed with mice deficient in interleukin (IL)-7, an essential cytokine for T and B cell development. Administration of hGM-CSF in these mice could not restore T or B lymphopoiesis, indicating that enforced GM-CSF signals cannot substitute for IL-7 to promote lymphopoiesis. Strikingly, >50% hGM-CSFR+ common lymphoid progenitors (CLPs) and >20% hGM-CSFR+ pro-T cells gave rise to granulocyte, monocyte, and/or myeloid dendritic cells, but not MegE lineage cells in the presence of hGM-CSF. Injection of hGM-CSF into mice transplanted with hGM-CSFR+ CLPs blocked their lymphoid differentiation, but induced development of GM cells in vivo. Thus, hGM-CSF transduces permissive signals for myeloerythroid differentiation, whereas it transmits potent instructive signals for the GM differentiation to CLPs and early T cell progenitors. These data suggest that a majority of CLPs and a fraction of pro-T cells possess plasticity for myelomonocytic differentiation that can be activated by ectopic GM-CSF signals, supporting the hypothesis that the down-regulation of GM-CSFR is a critical event in producing cells with a lymphoid-restricted lineage potential.
Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice.
Authors: S Izui, G Fernandes, I Hara, P J McConahey, F C Jensen, F J Dixon, R A Good
Journal: The Journal of Experimental Medicine (1981)

The effect of dietary restriction on the expression of retroviral envelope glycoprotein, gp70, and the formation of gp70-anti gp70 immune complexes was investigated in lupus-prone NZB x NZW F1 hybrid mice. Restricting total calorie intake from the usual 20 to only 10 calories per day after weaning markedly reduced serum levels of both free and antibody-complexed gp70, prevented renal disease, and increased the life spans of these mice. The reduction in serum gp70 was evident after only 2 wk of feeding these animals the low-calorie diet, and the concentration remained virtually unchanged throughout the course of 10 mon experimentation. However, serum concentrations of the major structural protein, p30, of endogenous retroviruses were not altered by restricting calories. Amounts of the serum glycoprotein, haptoglobin, decreased parallel to those of gp70 but amounts of albumin did not. These results suggest that the expression of gp70 in serum is controlled independently of the production of complete viral particles, and regulated by a mechanism similar to that for other serum glycoproteins, such as haptoglobin.
Fas ligand mediates activation-induced cell death in human T lymphocytes.
Authors: M R Alderson, T W Tough, T Davis-Smith, S Braddy, B Falk, K A Schooley, R G Goodwin, C A Smith, F Ramsdell, D H Lynch
Journal: The Journal of Experimental Medicine (1995)

A significant proportion of previously activated human T cells undergo apoptosis when triggered through the CD3/T cell receptor complex, a process termed activation-induced cell death (AICD). Ligation of Fas on activated T cells by either Fas antibodies or recombinant human Fas-ligand (Fas-L) also results in cytolysis. We demonstrate that these two pathways of apoptosis are causally related. Stimulation of previously activated T cells resulted in the expression of Fas-L mRNA and lysis of Fas-positive target cells. Fas-L antagonists inhibited AICD of T cell clones and staphylococcus enterotoxin B (SEB)-specific T cell lines. The data indicate AICD in previously stimulated T cells is mediated by Fas/Fas-L interactions.