tbuckley/cabot-search huggingface dataset:
Evolution of Elongation Factor G and the Origins of Mitochondrial and Chloroplast Forms
Authors: G. C. Atkinson, S. L. Baldauf
Journal: Molecular Biology and Evolution (2010)

Protein synthesis elongation factor G (EF-G) is an essential protein with central roles in both the elongation and ribosome recycling phases of protein synthesis. Although EF-G evolution is predicted to be conservative, recent reports suggest otherwise. We have characterized EF-G in terms of its molecular phylogeny, genomic context, and patterns of amino acid substitution. We find that most bacteria carry a single "canonical" EF-G, which is phylogenetically conservative and encoded in an str operon. However, we also find a number of EF-G paralogs. These include a pair of EF-Gs that are mostly found together and in an eclectic subset of bacteria, specifically δ-proteobacteria, spirochaetes, and planctomycetes (the "spd" bacteria). These spdEFGs have also given rise to the mitochondrial factors mtEFG1 and mtEFG2, which probably arrived in eukaryotes before the eukaryotic last common ancestor. Meanwhile, chloroplasts apparently use an α-proteobacterial–derived EF-G rather than the expected cyanobacterial form. The long-term comaintenance of the spd/mtEFGs may be related to their subfunctionalization for translocation and ribosome recycling. Consistent with this, patterns of sequence conservation and site-specific evolutionary rate shifts suggest that the faster evolving spd/mtEFG2 has lost translocation function, but surprisingly, the protein also shows little conservation of sites related to recycling activity. On the other hand, spd/mtEFG1, although more slowly evolving, shows signs of substantial remodeling. This is particularly extensive in the GTPase domain, including a highly conserved three amino acid insertion in switch I. We suggest that subfunctionalization of the spd/mtEFGs is not a simple case of specialization for subsets of original activities. Rather, the duplication allows the release of one paralog from the selective constraints imposed by dual functionality, thus allowing it to become more highly specialized. Thus, the potential for fine tuning afforded by subfunctionalization may explain the maintenance of EF-G paralogs.
Estrogen Inhibits Vascular Calcification via Vascular RANKL System
Authors: Mariana Kiomy Osako, Hironori Nakagami, Nobutaka Koibuchi, Hideo Shimizu, Futoshi Nakagami, Hiroshi Koriyama, Munehisa Shimamura, Takashi Miyake, Hiromi Rakugi, Ryuichi Morishita
Journal: Circulation Research (2010)

Arterial calcification and osteoporosis are associated in postmenopausal women. RANK (the receptor activator of nuclear factor kappaB), RANKL (RANK ligand), and osteoprotegerin are key proteins in bone metabolism and have been found at the site of aortic calcification. The role of these proteins in vasculature, as well as the contribution of estrogen to vascular calcification, is poorly understood.To clarify the mechanism of RANKL system to vascular calcification in the context of estrogen deficiency.RANKL induced the calcification inducer bone morphogenetic protein-2 by human aortic endothelial cells (HAECs) and decreased the calcification inhibitor matrix Gla protein (MGP) in human aortic smooth muscle cells (HASMCs), as quantified by real-time PCR and Western blot analysis. RANKL also induced bone-related gene mRNA expression and calcium deposition (Alizarin red staining) followed by the osteogenic differentiation of HASMCs. Estrogen inhibited RANKL signaling in HAECs and HASMCs mainly through estrogen receptor alpha. Apolipoprotein E-deficient mice fed with Western high-fat diet for 3 months presented atherosclerotic calcification (Oil red and Alizarin red staining) and osteoporosis (microcomputed tomographic analysis) after ovariectomy and increased expression of RANKL, RANK, and osteopontin in atherosclerotic lesion, as detected by in situ hybridization. Estrogen replacement inhibited osteoporosis and the bone morphogenetic protein osteogenic pathway in aorta by decreasing phosphorylation of smad-1/5/8 and increasing MGP mRNA expression.RANKL contributes to vascular calcification by regulating bone morphogenetic protein-2 and MGP expression, as well as bone-related proteins, and is counteracted by estrogen in a receptor-dependent manner.
Short-term effects of air pollution on daily asthma emergency room admissions
Authors: I. Galán, A. Tobías, J.R. Banegas, E. Aránguez
Journal: European Respiratory Journal (2003)

Many time-series studies have shown positive associations between air pollutants and asthma morbidity. However, few studies have included pollen as a potential confounder when examining this relationship. This study analysed the short-term association between air pollutants (sulphur dioxide (SO2), particles measured with a median aerodynamic diameter of <10 microm (PM10), nitrogen dioxide (NO2) and ozone (O3)) and asthma emergency room admissions in Madrid, Spain, in 1995-1998, adjusting for four types of pollen with allergenic potential (Olea europaea, Plantago sp., Poaceae and Urticaceae). Data were analysed using autoregressive Poisson regression and generalised additive models (GAM). The strongest associations were observed at 1 day lag for O3, and 3 days lag for the remaining pollutants. Using Poisson regression, a single-pollutant model showed that a 10-microg x m(-3) rise in pollutant level led to relative risks of: 1.039 for PM10; 1.029 for SO2; 1.033 for NO2; and 1.045 for O3. Adjustment for the different types of pollen led to no substantial variation in these associations. In the multipollutant models for cold-season pollutants (including PM10, SO2 and the four types of pollen) and photochemical pollutants (including NO2, O3 and the four types of pollen) the associations for PM10, NO2 and O3 held, but no relationship with SO2 was evident. GAM analysis yielded the same results, both in terms of lags and of quantification of the effect for all pollutants. In conclusion, the usual air pollution levels in Madrid were associated with an increase in asthma emergency room admissions, and this association remained controlling for the presence of ambient pollen.
The effects of antiarrhythmic drugs, stimulation frequency, and potassium-induced resting membrane potential changes on conduction velocity and dV/dtmax in guinea pig myocardium.
Authors: J W Buchanan, T Saito, L S Gettes
Journal: Circulation Research (1985)

For one-dimensional propagation, a nonlinear relationship between Vmax and conduction velocity is predicted by cable theory, and, under experimental conditions, Vmax and conduction velocity may change in opposite directions. Using standard microelectrode techniques, we have measured Vmax and conduction velocity in guinea pig papillary muscles exposed to tetrodotoxin and low sodium (agents expected primarily to decrease, directly, the rapid inward current), increased extracellular potassium (an agent which decreases the rapid inward current at least partially by inactivation mediated by depolarization of the resting membrane potential), and, over a wide range of stimulation frequencies, the antiarrhythmic drugs, quinidine, lidocaine, and procainamide. In all cases, except for the region of potassium-induced "supernormal conduction" between 5.4 and 9 mM, Vmax and conduction velocity varied as predicted by one-dimensional cable theory; that is, changes in Vmax were always proportional to changes in the square of conduction velocity. We conclude that the relationship between Vmax and conduction velocity predicted by cable theory occurs experimentally in guinea pig papillary muscle subjected to commonly used antiarrhythmic drugs and other interventions expected to reduce the sodium inward current. This relationship may be useful in applying known effects of drugs on Vmax to action potential propagation.
Systems Biologists Seek Fuller Integration of Systems Biology Approaches in New Cancer Research Programs
Authors: Olaf Wolkenhauer, Charles Auffray, Simone Baltrusch, Nils Blüthgen, Helen Byrne, Marta Cascante, Andrea Ciliberto, Trevor Dale, Dirk Drasdo, David Fell, James E. Ferrell, Daniel Gallahan, Robert Gatenby, Ulrich Günther, Brian D. Harms, Hanspeter Herzel, Christian Junghanss, Manfred Kunz, Ingeborg van Leeuwen, Philippe Lenormand, Francis Levi, Michael Linnebacher, John Lowengrub, Philip K. Maini, Arif Malik, Katja Rateitschak, Owen Sansom, Reinhold Schäfer, Karsten Schürrle, Christine Sers, Santiago Schnell, Darryl Shibata, John Tyson, Julio Vera, Michael White, Boris Zhivotovsky, Robert Jaster
Journal: Cancer Research (2009)

Abstract Systems biology takes an interdisciplinary approach to the systematic study of complex interactions in biological systems. This approach seeks to decipher the emergent behaviors of complex systems rather than focusing only on their constituent properties. As an increasing number of examples illustrate the value of systems biology approaches to understand the initiation, progression, and treatment of cancer, systems biologists from across Europe and the United States hope for changes in the way their field is currently perceived among cancer researchers. In a recent EU-US workshop, supported by the European Commission, the German Federal Ministry for Education and Research, and the National Cancer Institute of the NIH, the participants discussed the strengths, weaknesses, hurdles, and opportunities in cancer systems biology. Cancer Res; 70(1); 12–3
Measurement of gluten using a monoclonal antibody to a coeliac toxic peptide of A gliadin
Authors: H J Ellis, S Rosen-Bronson, N O’Reilly, P J Ciclitira
Journal: Gut (1998)

Background —Future European Community regulations will require a sensitive and specific assay for measurement of coeliac toxic gluten proteins in foods marketed as gluten-free. To avoid spurious cross reactions with non-toxic proteins, specific antibodies and target antigens are required. A synthetic 19 amino acid peptide of A gliadin has been shown to cause deterioration in the morphology of small intestinal biopsy specimens of coeliac patients in remission. Aims —To develop an assay for detection of gluten in foods, based on measurement of a known toxic peptide. Methods —A monoclonal antibody raised against the toxic A gliadin peptide, with a polyclonal anti-unfractionated gliadin capture antibody, was used to develop a double sandwich enzyme linked immunosorbent assay (ELISA) for the measurement of gluten in foods. Results —Standard curves for gliadin and for rye, barley, and oat prolamins were produced. The sensitivity of the assay was 4 ng/ml of gliadin, 500 ng/ml for rye prolamins, and 1000 ng/ml for oat and barley prolamins. The assay could detect gluten in cooked foods, although at reduced sensitivity. Prolamins from coeliac non-toxic rice, maize, millet, and sorghum did not cross react in the assay. A variety of commercially available gluten- free foods were analysed; small quantities of gluten were detected in some products. Conclusion —The assay may form the basis of a sensitive method for measurement of gluten in foods for consumption by patients with coeliac disease.
Availability of Consumer Prices From US Hospitals for a Common Surgical Procedure
Authors: Jaime A. Rosenthal, Xin Lu, Peter Cram
Journal: JAMA Internal Medicine (2013)

Importance: Many proposals for health care reform incentivize patients to play a more active role in selecting health care providers on the basis of quality and price.While data on quality are increasingly available, availability of pricing data is uncertain.Objective: To examine whether we could obtain pricing data for a common elective surgical procedure, total hip arthroplasty (THA).Design: We randomly selected 2 hospitals from each state (plus Washington, DC) that perform THA, as well as the 20 top-ranked orthopedic hospitals according to US News and World Report rankings.We contacted each hospital by telephone between May 2011 and July 2012.Using a standardized script, we requested from each hospital the lowest complete "bundled price" (hospital plus physician fees) for an elective THA that was required by one of the author's 62-year-old grandmother.In our scenario, the grandmother did not have insurance but had the means to pay out of pocket.We explained that we were seeking the lowest complete price for the procedure.When we encountered hospitals that could provide the hospital fee only, we contacted a random hospital affiliated orthopedic surgery practice to obtain the physician fee.Each hospital was contacted up to 5 times in efforts to obtain pricing information.Setting/Participants: All top-ranked and a sample of non-top-ranked US hospitals performing THA.Main Outcome Measures: Percentage of hospitals able to provide a complete price estimate for THA (physician and hospital fee) for top-ranked and non-topranked hospitals and range of prices quoted by each group.Results: Nine top-ranked hospitals (45%) and 10 nontop-ranked hospitals (10%) were able to provide a complete bundled price (PϽ .001).We were able to obtain a complete price estimate from an additional 3 topranked hospitals (15%) and 54 non-top-ranked hospitals (53%) (P=.002) by contacting the hospital and physician separately.The range of complete prices was wide for both top-ranked ($12 500-$105 000) and non-topranked hospitals ($11 100-$125 798). Conclusions and Relevance:We found it difficult to obtain price information for THA and observed wide variation in the prices that were quoted.Many health care providers cannot provide reasonable price estimates.Patients seeking elective THA may find considerable price savings through comparison shopping.
Building of the global movement for health equity: from Santiago to Rio and beyond
Authors: Michael Marmot, Jessica Allen, Ruth Bell, Peter Goldblatt
Journal: The Lancet (2011)

Health inequalities are present throughout the world, both within and between countries. The Commission on Social Determinants of Health drew attention to dramatic social gradients in health within most countries and made proposals for action. These inequalities are not inevitable. The purpose of this article is to report on activity that has taken place worldwide after the report by the Commission on Social Determinants of Health. First, we summarise the global situation. Second, we summarise an interim report of the emerging findings from an independent review of social determinants and the health divide, which was commissioned by the WHO European region. The world conference on social determinants of health will be held in Rio de Janeiro, Brazil, in October, 2011. This summit provides an opportunity to galvanise support, prioritise action, and respond to the call by the Commission on Social Determinants of Health for social justice as a route to a fair distribution of health.
CARDIAC LESIONS PRODUCED IN RABBITS BY MASSIVE INJECTIONS OF BOVINE SERUM GAMMA GLOBULIN
Authors: Robert H. More, Douglas Waugh, Sidney D. Kobernick
Journal: The Journal of Experimental Medicine (1949)

Granulomatous lesions of the valves and valve rings have been produced in 52 per cent of rabbits treated by massive intravenous administrations of bovine gamma globulin in such a way as to establish a state of anaphylactic hypersensitivity in the animals. The incidence of the lesions is greater than has heretofore been reported as produced by the use of any type of foreign protein injection in rabbits. The use of a purified protein antigen has resulted in the production of several different types of lesions; namely, a granulomatous inflammation of heart valves and valve rings, a glomerulonephritis, and an arteritis. The lesions of the heart cannot be regarded as being identical with the lesions of human rheumatic fever, but they are considered to be sufficiently similar to warrant a continuation of this approach to the study of the etiology and pathogenesis of rheumatic fever in man.
Validating non-invasive markers of fibrosis: the need for a new histological reference standard
Authors: E. A. Tsochatzis, P. Manousou, G. Fede, A. P. Dhillon, A. K. Burroughs
Journal: Gut (2010)

We read with interest the article by Parkes et al in Gut 1 and fully agree with the authors' aims in evaluating the performance of a non-invasive marker of fibrosis, the enhanced liver fibrosis (ELF) test, with respect to clinically meaningful end points of liver-related complications and mortality. However, we believe that the methodology used is inappropriate and has led to potentially misleading conclusions.

The authors have previously shown that ‘severe fibrosis’, i.e. stage 3 (‘bridging fibrosis’) and 4 (cirrhosis) in patients with non-alcoholic steatohepatitis is better predicted by an ELF panel score of 9.9–10.35.2 They also showed that ELF scores are not significantly different between different liver disease aetiologies. In this paper,1 they …
Spanish abortion law comes under threat as opposition groups win judicial review
Authors: M. de Lago
Journal: BMJ (2010)

A new law that legalises abortion on demand in Spain for the first time and came into force on July 5 could be suspended and delayed for months or years as opposition groups demand a judicial review.

Two appeals have been lodged with the Spanish Constitutional Court, which has the power to abolish laws it finds unconstitutional. The appeals are from the conservative Popular Party—the strongest group in opposition—and the regional government of Navarre. The court has agreed to review the law and has set a two week deadline …
Selective Inhibition of Ras, Phosphoinositide 3 Kinase, and Akt Isoforms Increases the Radiosensitivity of Human Carcinoma Cell Lines
Authors: In-Ah Kim, Sun-Sik Bae, Annemarie Fernandes, JunMin Wu, Ruth J. Muschel, W. Gillies McKenna, Morris J. Birnbaum, Eric J. Bernhard
Journal: Cancer Research (2005)

Abstract Ras activation promotes the survival of tumor cells after DNA damage. To reverse this survival advantage, Ras signaling has been targeted for inhibition. Other contributors to Ras-mediated DNA damage survival have been identified using pharmacologic inhibition of signaling, but this approach is limited by the specificity of the inhibitors used and their toxicity. To better define components of Ras signaling that could be inhibited in a clinical setting, RNA interference was used to selectively block expression of specific isoforms of Ras, phosphoinositide 3 (PI3) kinase, and Akt. Inhibition of oncogenic Ras expression decreased both phospho-Akt and phospho-p42/44 mitogen-activated protein (MAP) kinase levels and reduced clonogenic survival. Because pharmacologic inhibition of PI3 kinases and Akt radiosensitized cell lines with active Ras signaling, whereas inhibition of the MAP/extracellular signal–regulated kinase (ERK) kinase/ERK pathway did not, we examined the contribution of PI3 kinases and Akts to radiation survival. Selective inhibition the PI3 kinase P110α + p85β isoforms reduced Akt phosphorylation and radiation survival. Similarly, inhibition of Akt-1 reduced tumor cell radiation survival. Inhibition of Akt-2 or Akt-3 had less effect. Retroviral transduction and overexpression of mouse Akt-1 was shown to rescue cells from inhibition of endogenous human Akt-1 expression. This study shows that Ras signaling to the PI3 kinase–Akt pathway is an important contributor to survival, whether Ras activation results from mutation of ras or overexpression of epidermal growth factor receptor. This study further shows that selective inhibition of the PI3 kinase P110α + p85β isoforms or Akt-1 could be a viable approach to sensitizing many tumor cells to cytotoxic therapies.
White Matter Differences Among Adolescents Reporting Psychotic Experiences
Authors: Erik O’Hanlon, Alexander Leemans, Ian Kelleher, Mary C. Clarke, Sarah Roddy, Helen Coughlan, Michelle Harley, Francesco Amico, Matthew J. Hoscheit, Lauren Tiedt, Javeria Tabish, Anna McGettigan, Thomas Frodl, Mary Cannon
Journal: JAMA Psychiatry (2015)

Abnormal brain connectivity is thought to have a key role in the pathophysiology of schizophrenia and other psychotic disorders. White matter (WM) abnormalities have been reported in patients with schizophrenia and patients with prodromal syndromes. To our knowledge, no studies have yet reported on WM differences among adolescents who report psychotic experiences, a known vulnerability group for later severe psychopathology, including psychotic illness.To study WM differences using diffusion-weighted imaging (whole-brain and tractography analyses) in adolescents who report psychotic experiences.A population-based case-control study of 28 adolescents 13 to 16 years old who reported psychotic experiences and a matched sample of 28 adolescents who did not report psychotic experiences drawn from a sample of 212 young people recruited from primary schools in North Dublin and Kildare, Ireland. The study dates were 2008 to 2011.High-angular resolution diffusion-weighted imaging data were used to conduct whole-brain WM analysis using tract-based spatial statistics. Based on this exploratory analysis, a tractography-based approach with constrained spherical deconvolution was performed.Compared with control group participants, adolescents who reported psychotic experiences showed WM differences bilaterally in striatal regions in proximity to the putamen (increased fractional anisotropy, P = .01, false discovery rate corrected), and tractography identified significant WM differences bilaterally in the uncinate fasciculus (increased fractional anisotropy in the right [P = .001] and axial diffusivity in the left [P = .01] uncinate fasciculus, respectively). Similar patterns of WM differences between groups survived adjustment for other psychopathology, indicating some specificity for psychotic experiences. Exploratory along-tract analyses showed WM differences between groups in the frontal projections of the right inferior fronto-occipital fasciculus (reduced radial diffusivity in approximately 32% of the tract segment [P ≤ .0001] and increased fractional anisotropy in approximately 16% of the tract segment [P ≤ .0009]).In a population-based study of adolescents reporting psychotic experiences, we found a number of WM differences in the region of the putamen located between the inferior fronto-occipital fasciculus and the uncinate fasciculus and in the left parietal regions that include the fiber bundle of the superior longitudinal fasciculus. These findings suggest that subtle structural changes to WM microstructure are not merely a consequence of disorder but may index vulnerability to psychosis even at a very early age.
Techniques for Studying Biliary Secretion: Electrolytes in Bile
Authors: Christine E. Bear, Steven M. Strasberg
Journal: Hepatology (1984)

A major limitation in understanding bile formation has been technical. The liver and ductular epithelium are relatively inaccessible, necessitating indirect techniques of uncertain validity. This is well seen in attempts to define the role of electrolyte secretion in bile. It is widely agreed that bile salts stimulate a component of canalicular flow and that inorganic electrolyte secretion is stimulated by bile salts. The choleretic efficiency of a bile salt is directly related to the magnitude of the electrolyte effect. But there is no consensus regarding how and where bile salts stimulate electrolyte secretion. Some evidence points to a paracellular route by processes of solvent drag and diffusion. Other studies suggest stimulation of specific transcellular electrolyte pathways. It has been believed that canalicular bile salt-independent bile flow is generated by active blood-to-bile electrolyte transport. Actually, available methods do not permit us to conclude with absolute certainty that there is canalicular bile salt-independent flow, although there is considerable evidence for it. New studies suggest that electrolyte transport in this type of flow is passive and that flow is due to transport of organic anions. Ductular flow does seem to be due to active transport of electrolytes, particularly bicarbonate. Better and more direct techniques are required to settle the controversies in this area.