tbuckley/cabot-search huggingface dataset:
Symbiotic Origin of a Novel Actin Gene in the Cryptophyte Pyrenomonas helgolandii
Authors: Thomas B. Stibitz, Patrick J. Keeling, Debashish Bhattacharya
Journal: Molecular Biology and Evolution (2000)

Cryptophytes are photosynthetic protists that have acquired their plastids through the secondary symbiotic uptake of a red alga. A remarkable feature of cryptophytes is that they maintain a reduced form of the red algal nucleus, the nucleomorph, between the second and third plastid membranes (periplastidial compartment; PC). The nucleomorph is thought to be a transition state in the evolution of secondary plastids, with this genome ultimately being lost when photosynthesis comes under full control of the “host” nucleus (e.g., as in heterokonts, haptophytes, and euglenophytes). Genes presently found in the nucleomorph seem to be restricted to those involved in its own maintenance and to that of the plastid; other genes were lost as the endosymbiont was progressively reduced to its present state. Surprisingly, we found that the cryptophyte Pyrenomonas helgolandii possesses a novel type of actin gene that originated from the nucleomorph genome of the symbiont. Our results demonstrate for the first time that secondary symbionts can contribute genes to the host lineage which are unrelated to plastid function. These genes are akin to the products of gene duplication or lateral transfer and provide a source of evolutionary novelty that can significantly increase the genetic diversity of the host lineage. We postulate that this may be a common phenomenon in algae containing secondary plastids that has yet to be fully appreciated due to a dearth of evolutionary studies of nuclear genes in these taxa.
Late (two-year) follow-up from the First-In-Man (FIM) experience after implantation of sirolimus-eluting stents
Authors: Jose Eduardo Sousaau, Alexandre Abizaid, Andrea Abizaid, Jeffrey Popma, Pim de Feyter, Fausto Feres, Marco Costa, Judith Jaeger, Luiz F. Tanajura, Ana C. Seixas, Ibraim Pinto, Luiz A. Mattos, Robert Falotico, Martin Leon, Patrick Serruys, Amanda Sousa
Journal: Journal of the American College of Cardiology (2002)
Ether à go-go Potassium Channels as Human Cervical Cancer Markers
Authors: Luz María Barajas Farias, Deysi Bermúdez Ocaña, Lorenza Díaz, Fernando Larrea, Euclides Avila-Chávez, Adriana Cadena, Luz María Hinojosa, Gerardo Lara, Luis Alberto Villanueva, Carlos Vargas, Elizabeth Hernández-Gallegos, Ignacio Camacho-Arroyo, Alfonso Dueñas-González, Enrique Pérez-Cárdenas, Luis A. Pardo, Angélica Morales, Lucía Taja-Chayeb, Juan Escamilla, Carmen Sánchez-Peña, Javier Camacho
Journal: Cancer Research (2004)

Abstract Ether à go-go (EAG) potassium channels display oncogenic properties. In normal tissues, EAG mRNA is almost exclusively expressed in brain, but it is expressed in several somatic cancer cell lines, including HeLa, from cervix. Antisense experiments against eag reduce cell proliferation in some cancer cell lines, and inhibition of EAG-mediated currents has been suggested to decrease cell proliferation in a melanoma cell line. Because of the potential clinical relevance of EAG, we investigated EAG mRNA expression in the following fresh samples from human uterine cervix: 5 primary cultures obtained from cancerous biopsies, 1 cancerous fresh tissue, and 12 biopsies of control normal tissue. All of the control cervical samples came from patients with negative pap smears. Reverse transcription-PCR and Southern-blot experiments revealed eag expression in 100% of the cancerous samples and in 33% of the normal biopsies. Immunochemistry experiments showed the presence of EAG channel protein in cells from the primary cultures and in cervical cancer biopsies sections from the same patients. In addition, we looked for EAG-mediated currents in the cultures from cervical cancer cells. Here we show for the first time EAG channel activity in human tumors. Patch-clamp recordings showed typical EAG-mediated currents modulated by magnesium and displaying a pronounced Cole-Moore shift. Because EAG expression and channel activity have been suggested to be important in cell proliferation, our findings strongly support the idea of considering EAG as a tumor marker as well as a potential membrane therapeutic target for cervical cancer.
CTGF Inhibits BMP-7 Signaling in Diabetic Nephropathy
Authors: Tri Q. Nguyen, Peggy Roestenberg, Frans A. van Nieuwenhoven, Niels Bovenschen, Zeke Li, Leon Xu, Noelynn Oliver, Jan Aten, Jaap A. Joles, Cecilia Vial, Enrique Brandan, Karen M. Lyons, Roel Goldschmeding
Journal: Journal of the American Society of Nephrology (2008)

In diabetic nephropathy, connective tissue growth factor (CTGF) is upregulated and bone morphogenetic protein 7 (BMP-7) is downregulated. CTGF is known to inhibit BMP-4, but similar cross-talk between BMP-7 and CTGF has not been studied. In this study, it was hypothesized that CTGF acts as an inhibitor of BMP-7 signaling activity in diabetic nephropathy. Compared with diabetic wild-type CTGF(+/+) mice, diabetic CTGF(+/-) mice had approximately 50% lower CTGF mRNA and protein, less severe albuminuria, no thickening of the glomerular basement membrane, and preserved matrix metalloproteinase (MMP) activity. Although the amount of BMP-7 mRNA was similar in the kidneys of diabetic CTGF(+/+) and CTGF(+/-) mice, phosphorylation of the BMP signal transduction protein Smad1/5 and expression of the BMP target gene Id1 were lower in diabetic CTGF(+/+) mice. Moreover, renal Id1 mRNA expression correlated with albuminuria (R = -0.86) and MMP activity (R = 0.76). In normoglycemic mice, intraperitoneal injection of CTGF led to a decrease of pSmad1/5 in the renal cortex. In cultured renal glomerular and tubulointerstitial cells, CTGF diminished BMP-7 signaling activity, evidenced by lower levels of pSmad1/5, Id1 mRNA, and BMP-responsive element-luciferase activity. Co-immunoprecipitation, solid-phase binding assay, and surface plasmon resonance analysis showed that CTGF binds BMP-7 with high affinity (Kd approximately 14 nM). In conclusion, upregulation of CTGF inhibits BMP-7 signal transduction in the diabetic kidney and contributes to altered gene transcription, reduced MMP activity, glomerular basement membrane thickening, and albuminuria, all of which are hallmarks of diabetic nephropathy.
Asynchronous Growth of Prostate Cancer Is Reflected by Circulating Tumor Cells Delivered from Distinct, Even Small Foci, Harboring Loss of Heterozygosity of the <i>PTEN</i> Gene
Authors: Hartmut Schmidt, Gabriela DeAngelis, Elke Eltze, Iris Gockel, Axel Semjonow, Burkhard Brandt
Journal: Cancer Research (2006)

Abstract The clinical value of prostate-specific antigen (PSA)–positive circulating tumor cells (CTCs) is still a matter of debate and it is also still unclear if these CTCs actually represent the primary tumor. Therefore, we isolated PSA-positive CTCs from the peripheral blood of patients suffering from multifocal cancers and did genetic profiling of each cancer focus by a multiplex PCR–based microsatellite analysis (D7S522, D8S522, NEFL, D10S541, D13S153, D16S400, D16S402, D16S422, and D17S855). In 17 of 20 prostate cancer cases, the loss of heterozygosity (LOH) pattern of the CTCs was identical with only one focus of the primary tumor. Moreover, in six cases, the LOH pattern suggested that smaller foci, down to 0.2 cm3, might deliver CTCs. Interestingly, the highest number of LOHs was observed at the marker D10S541 (85%), the PTEN gene, which was observed much less frequently in unifocal prostate cancer (48%). Furthermore, the infrequently occurring LOH in the BRCA1 gene (38%) was found in four of the five cases where a biochemical recurrence was seen within 3 years after prostatectomy. Therefore, the data might support the assumption that CTCs in prostate cancer are derived from distinct foci of a primary tumor. The size of the tumor focus is not related to the delivery of cells. Although the number of cases that were investigated in this study was small, it might be suggested that the LOH at distinct markers such as D10S541 and D17S855 represent the genes PTEN and BRCA1, which might be associated with the occurrence of CTCs in the peripheral blood of patients as well as an early biochemical recurrence. (Cancer Res 2006; 66(18): 8959-65)
Adverse drug reactions: finding the needle in the haystack
Authors: I R. Edwards
Journal: BMJ (1997)

Patients need to be sure that the medicines they take are as safe and effective as possible. Concerns over a product's safe use must be discovered, evaluated, and acted on, and the results made available for patient care as expeditiously as possible. In this process spontaneous reports of adverse reactions play an important part, but the problem they present is that of finding needles—true adverse reactions—in large haystacks of suspicions.

There is no substitute for spontaneous adverse drug reaction reports for providing early signals of problems with drugs. The article in this week's issue by Lee et al shows that reporting by pharmacists can make a difference to the number of meaningful reports from hospitals (p 519).1 Britain thus joins 36 other countries in the World Health Organisation's programme on international drug monitoring that accept reports from pharmacists. Britain …
High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients
Authors: Katharina Ilm, Wolfgang Kemmner, Marc Osterland, Susen Burock, Gudrun Koch, Pia Herrmann, Peter M Schlag, Ulrike Stein
Journal: Molecular Cancer (2015)

The metastasis-associated in colon cancer 1 (MACC1) gene has been identified as prognostic biomarker for colorectal cancer (CRC). Here, we aimed at the refinement of risk assessment by separate and combined survival analyses of MACC1 expression with any of the markers KRAS mutated in codon 12 (KRAS G12) or codon 13 (KRAS G13), BRAF V600 mutation and MSI status in a retrospective study of 99 CRC patients with tumors UICC staged I, II and III. We showed that only high MACC1 expression (HR: 6.09, 95% CI: 2.50-14.85, P < 0.001) and KRAS G13 mutation (HR: 5.19, 95% CI: 1.06-25.45, P = 0.042) were independent prognostic markers for shorter metastasis-free survival (MFS). Accordingly, Cox regression analysis revealed that patients with high MACC1 expression and KRAS G13 mutation exhibited the worst prognosis (HR: 14.48, 95% CI: 3.37-62.18, P < 0.001). Patients were classified based on their molecular characteristics into four clusters with significant differences in MFS (P = 0.003) by using the SPSS 2-step cluster function and Kaplan-Meier survival analysis. According to our results, patients with high MACC1 expression and mutated KRAS G13 exhibited the highest risk for metachronous metastases formation. Moreover, we demonstrated that the "Traditional pathway" with an intermediate risk for metastasis formation can be further subdivided by assessing MACC1 expression into a low and high risk group with regard to MFS prognosis. This is the first report showing that identification of CRC patients at high risk for metastasis is possible by assessing MACC1 expression in combination with KRAS G13 mutation.
Self-control observed
Authors: Howard Rachlin
Journal: Behavioral and Brain Sciences (1995)

Abstract Complex cases of self-control involve processes such as guilt-avoidance, inhibition, self-punishment, conscious thought, free will, and imagination. Such processes, conceived as internal mediating mechanisms, serve the function in psychological theory of avoiding teleological causation. Acceptance of the scientific legitimacy of teleological behaviorism would obviate the need for internal mediation, redefine the above processes in terms of temporally extended patterns of overt behavior, and clarify their relation to selfcontrol.
microRNA miR-196a-2 and Breast Cancer: A Genetic and Epigenetic Association Study and Functional Analysis
Authors: Aaron E. Hoffman, Tongzhang Zheng, Chunhui Yi, Derek Leaderer, Joanne Weidhaas, Frank Slack, Yawei Zhang, Trupti Paranjape, Yong Zhu
Journal: Cancer Research (2009)

Increasing evidence has suggested that microRNAs (miRNA) play an important role in tumorigenesis. As transcriptional regulators, altered miRNA expression may affect many cancer-related biological pathways, indicating that miRNAs can function as tumor suppressors and/or oncogenes. We first performed a genetic association analysis by screening genetic variants in 15 miRNA genes and detected that a common sequence variant in hsa-miR-196a-2 (rs11614913, C-->T) was significantly associated with decreased breast cancer risk (for homozygous variant: odds ratio, 0.44; 95% confidence interval, 0.28-0.70). Hypermethylation of a CpG island upstream (-700 bp) of the miR-196a-2 precursor was also associated with reduced breast cancer risk (odds ratio, 0.35; 95% confidence interval, 0.15-0.81). By delivering expression vectors containing either wild-type or mutant precursors of miR-196a-2 into breast cancer cells, we showed that this variant led to less efficient processing of the miRNA precursor to its mature form as well as diminished capacity to regulate target genes. A whole-genome expression microarray was done and a pathway-based analysis identified a cancer-relevant network formed by genes significantly altered following enforced expression of miR-196a-2. Mutagenesis analysis further showed that cell cycle response to mutagen challenge was significantly enhanced in cells treated with variant miR-196a-2 compared with cells treated with the wild-type. Taken together, our findings suggest that miR-196a-2 might have a potentially oncogenic role in breast tumorigenesis, and the functional genetic variant in its mature region could serve as a novel biomarker for breast cancer susceptibility.
GSK-3β in mouse fibroblasts controls wound healing and fibrosis through an endothelin-1–dependent mechanism
Authors: Mohit Kapoor, Shangxi Liu, Xu Shi-wen, Kun Huh, Matthew McCann, Christopher P. Denton, James R. Woodgett, David J. Abraham, Andrew Leask
Journal: Journal of Clinical Investigation (2008)

Glycogen synthase kinase–3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by 2 genes, GSK3A and GSK3B. GSK-3 is thought to be involved in tissue repair and fibrogenesis, but its role in these processes is currently unknown. To investigate the function of GSK-3β in fibroblasts, we generated mice harboring a fibroblast-specific deletion of Gsk3b and evaluated their wound-healing and fibrogenic responses. We have shown that Gsk3b-conditional-KO mice (Gsk3b-CKO mice) exhibited accelerated wound closure, increased fibrogenesis, and excessive scarring compared with control mice. In addition, Gsk3b-CKO mice showed elevated collagen production, decreased cell apoptosis, elevated levels of profibrotic α-SMA, and increased myofibroblast formation during wound healing. In cultured Gsk3b-CKO fibroblasts, adhesion, spreading, migration, and contraction were enhanced. Both Gsk3b-CKO mice and fibroblasts showed elevated expression and production of endothelin-1 (ET-1) compared with control mice and cells. Antagonizing ET-1 reversed the phenotype of Gsk3b-CKO fibroblasts and mice. Thus, GSK-3β appears to control the progression of wound healing and fibrosis by modulating ET-1 levels. These results suggest that targeting the GSK-3β pathway or ET-1 may be of benefit in controlling tissue repair and fibrogenic responses in vivo.
Systemic lupus erythematosus. I. Outcome and survival: Dutch experience with 110 patients studied prospectively.
Authors: A.J Swaak, J.C Nossent, W Bronsveld, A Van Rooyen, E.J Nieuwenhuys, L Theuns, R.J Smeenk
Journal: Annals of the Rheumatic Diseases (1989)

This report presents an analysis of the cumulative survival in 110 well defined patients with systemic lupus erythematosus (SLE) who were followed up over a prolonged period of time. Special attention was paid to possible differences between patients who died and those who were still alive at the end of the study. Of the 110 patients with SLE, 96 (87%) were still alive after 10 years; the cumulative survival for men was 69% (11/16) and for women 90% (85/94). Patients who never developed a new exacerbation after the diagnosis for SLE had been established had a 10 year survival of 100%; for patients with one, two, or three exacerbations the 10 year survival was 91%, 69%, and 33% respectively. From these prospective studies it was found that the exacerbation frequency is most closely related to survival. Disease symptoms of renal involvement or neurological involvement, or both, present at the onset or at the moment the SLE diagnosis was established, were predominantly seen in patients who died during the follow up.
Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats
Authors: KL So, E de Buijzer, D Gommers, U Kaisers, PJ van Genderen, B Lachmann
Journal: European Respiratory Journal (1998)

Paraquat is a weed killer which causes often fatal lung damage in humans and other animals. There is evidence that the pulmonary surfactant system is involved in the pathophysiology of respiratory failure after paraquat intoxication and, therefore, the possible therapeutic effect of intratracheal surfactant administration on gas exchange in rats with progressive lung injury induced by paraquat poisoning was studied. In one group of rats, the time course of the development of lung injury due to paraquat intoxication was characterized. In a second group of rats, 72 h after paraquat intoxication, the animals underwent mechanical ventilation and only those animals in which the arterial oxygen tension/inspiratory oxygen fraction (Pa,O2/FI,O2) decreased to below 20 kPa (150 mmHg) received exogenous surfactant (200 mg x kg(-1) body weight). Within 3 days the rats in group 1 developed progressive respiratory failure, demonstrated not only by impaired gas exchange and lung mechanics but also by increased minimal surface tension and increased protein concentration in bronchoalveolar lavage fluid. In group 2, intratracheal surfactant administration increased Pa,O2/FI,O2 significantly within 5 min (14.4+/-2.4 kPa (108+/-18 mmHg)) to (55.2+/-53 kPa (414+/-40 mmHg)) and sustained this level for at least 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of severe respiratory failure caused by paraquat poisoning.
Effect of Blinded Peer Review on Abstract Acceptance
Authors: Joseph S. Ross, Cary P. Gross, Mayur M. Desai, Yuling Hong, Augustus O. Grant, Stephen R. Daniels, Vladimir C. Hachinski, Raymond J. Gibbons, Timothy J. Gardner, Harlan M. Krumholz
Journal: JAMA (2006)

Peer review should evaluate the merit and quality of abstracts but may be biased by geographic location or institutional prestige. The effectiveness of blinded peer review at reducing bias is unknown. To evaluate the effect of blinded review on the association between abstract characteristics and likelihood of abstract acceptance at a national research meeting. All abstracts submitted to the American Heart Association's annual Scientific Sessions research meeting from 2000-2004. Abstract review included the author's name and institution (open review) from 2000-2001, and this information was concealed (blinded review) from 2002-2004. Abstracts were categorized by country, primary language, institution prestige, author sex, and government and industry status. Likelihood of abstract acceptance during open and blinded review, by abstract characteristics. The mean number of abstracts submitted each year for evaluation was 13,455 and 28.5% were accepted. During open review, 40.8% of US and 22.6% of non-US abstracts were accepted (relative risk [RR], 1.81; 95% confidence interval [CI], 1.75-1.88), whereas during blinded review, 33.4% of US and 23.7% of non-US abstracts were accepted (RR, 1.41; 95% CI, 1.37-1.45; P<.001 for comparison between peer review periods). Among non-US abstracts, during open review, 31.1% from English- speaking countries and 20.9% from non-English-speaking countries were accepted (RR, 1.49; 95% CI, 1.39-1.59), whereas during blinded review, 28.8% and 22.8% of abstracts were accepted, respectively (RR, 1.26; 95% CI, 1.19-1.34; P<.001). Among abstracts from US academic institutions, during open review, 51.3% from highly prestigious and 32.6% from nonprestigious institutions were accepted (RR, 1.57; 95% CI, 1.48-1.67), whereas during blinded review, 38.8% and 29.0% of abstracts were accepted, respectively (RR, 1.34; 95% CI, 1.26-1.41; P<.001). This study provides evidence of bias in the open review of abstracts, favoring authors from the United States, English-speaking countries outside the United States, and prestigious academic institutions. Moreover, blinded review at least partially reduced reviewer bias.
Oxygen/nitrogen radicals. Lung injury and disease
Authors: P.S. Hiemstra
Journal: European Respiratory Journal (2005)

Oxygen/nitrogen radicals. Lung injury and disease     Lung Biology in Health and Disease, Volume 187     Edited by V. Vallyathan, V. Castranova and X. Shi     Published by Marcel Dekker Inc, 2004     Pages: 529. Price: £104.00, $195. ISBN 0-8247-4874-3

This 187th volume in Marcel Dekker's impressive series “Lung Biology in Health and Disease” covers the role of oxygen and nitrogen radicals in cell signalling, pathogenesis of lung disease and discusses treatment options based on increased knowledge within the field. The editors have a good track record in the research field, …
Retinal and Cerebral Microembolization During Coronary Artery Bypass Surgery
Authors: Raimondo Ascione, Arup Ghosh, Barnaby C. Reeves, John Arnold, Mike Potts, Atul Shah, Gianni D. Angelini
Journal: Circulation (2005)

Background— We sought to compare the effects on ophthalmic function of coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and off-pump (OPCAB) grafting and to investigate whether retinal microvascular damage is associated with markers of cerebral injury. Methods and Results— Retinal microvascular damage was assessed by fluorescein angiography and color fundus photography. Ophthalmic function was tested by the logarithm of the minimum angle of resolution visual acuity (VA), and cerebral injury, by transcranial Doppler ultrasound–detected emboli and S100 protein values. Twenty patients were randomized. Fluorescein angiography and postoperative VA could not be obtained for 1 CABG-CPB patient. Retinal microvascular damage was detected in 5 of 9 CABG-CPB but in none of 10 OPCAB patients (risk difference, 55%; 95% confidence interval [CI], 23% to 88%; P =0.01). Color fundus photography detected microvascular damage in 1 CABG-CPB patient but in no OPCAB patients; this lesion was associated with a field defect, which remained after 3 months of follow-up. There was no difference in postoperative VA. Doppler high-intensity transient signals (HITS) were 20.3 times more frequent in the CABG-CPB than in the OPCAB group (95% CI, 9.1 to 45; P &lt;0.0001). Protein S100 levels were higher in the CABG-CPB than in the OPCAB group 1 hour after surgery ( P &lt;0.001). HITS were 14.7 times more frequent (95% CI, 3.5 to 62; P =0.001) and S100 level 2.1 times higher (95% CI, 1.3 to 3.5; P =0.005) when retinal microvascular damage was present. Conclusions— The relative frequency of retinal microvascular damage between groups shows the extent to which the risk of cerebral injury is reduced with OPCAB. Imaging of part of the cerebral circulation provides evidence to validate markers of cerebral injury.