tbuckley/cabot-search huggingface dataset:
Ancient Duplications and Expression Divergence in the Globin Gene Superfamily of Vertebrates: Insights from the Elephant Shark Genome and Transcriptome
Authors: Juan C. Opazo, Alison P. Lee, Federico G. Hoffmann, Jessica Toloza-Villalobos, Thorsten Burmester, Byrappa Venkatesh, Jay F. Storz
Journal: Molecular Biology and Evolution (2015)

Comparative analyses of vertebrate genomes continue to uncover a surprising diversity of genes in the globin gene superfamily, some of which have very restricted phyletic distributions despite their antiquity. Genomic analysis of the globin gene repertoire of cartilaginous fish (Chondrichthyes) should be especially informative about the duplicative origins and ancestral functions of vertebrate globins, as divergence between Chondrichthyes and bony vertebrates represents the most basal split within the jawed vertebrates. Here, we report a comparative genomic analysis of the vertebrate globin gene family that includes the complete globin gene repertoire of the elephant shark (Callorhinchus milii). Using genomic sequence data from representatives of all major vertebrate classes, integrated analyses of conserved synteny and phylogenetic relationships revealed that the last common ancestor of vertebrates possessed a repertoire of at least seven globin genes: single copies of androglobin and neuroglobin, four paralogous copies of globin X, and the single-copy progenitor of the entire set of vertebrate-specific globins. Combined with expression data, the genomic inventory of elephant shark globins yielded four especially surprising findings: 1) there is no trace of the neuroglobin gene (a highly conserved gene that is present in all other jawed vertebrates that have been examined to date), 2) myoglobin is highly expressed in heart, but not in skeletal muscle (reflecting a possible ancestral condition in vertebrates with single-circuit circulatory systems), 3) elephant shark possesses two highly divergent globin X paralogs, one of which is preferentially expressed in gonads, and 4) elephant shark possesses two structurally distinct α-globin paralogs, one of which is preferentially expressed in the brain. Expression profiles of elephant shark globin genes reveal distinct specializations of function relative to orthologs in bony vertebrates and suggest hypotheses about ancestral functions of vertebrate globins.
Parvovirus B19–Associated Active Myocarditis With Biventricular Thrombi Results of Endomyocardial Biopsy Investigations and Cardiac Magnetic Resonance Imaging
Authors: Michel Noutsias, Uwe Kuehl, Dirk Lassner, Ulrich Gross, Matthias Pauschinger, Heinz-Peter Schultheiss, Matthias Gutberlet
Journal: Circulation (2007)
Endothelins: Homeostatic and Compensatory Actions in the Circulatory and Endocrine Systems
Authors: TOMOH MASAKI
Journal: Endocrine Reviews (1993)

ENDOTHELIN (ET) is a potent vasoconstrictive peptide which was originally isolated from the conditioned medium of cultured endothelial cells (1). It comprises 21 aminoacid residues, including four cysteine residues that form two disulfide bonds (see Fig. 1). ET elicits a sustained pressor response when administrated intravenously, which suggests its importance in blood pressure maintenance and generation of vasospasm. Accordingly, many investigators have been interested in this peptide. Analysis of ET genes revealed the existence of three distinct ET genes that encode different mature ET sequences, designated endothelin-1 (ET-1), ET-2, and ET-3 (Fig. 1) (2). Two and six amino acid residues of ET-1 are replaced in ET-2 and ET-3, respectively. There are no species differences among isoforms of human, porcine, rat, bovine, or dog. Interestingly, the structure of snake venom sarafotoxins are very similar to those of ETs. In endothelial cells, ET-1 is predominant, but ET-2 and ET-3 are not detected. As such, the question arose whether ET-2 and ET-3 are expressed in other tissues. Searching for complementary DNA (cDNA) clones of ET-2 and ET-3 in the cDNA library of human jejunum revealed the existence of all three cDNAs. Subsequent Northern blot analysis demonstrated that the three isoform messenger RNAs (mRNAs) are distributed widely throughout many tissues in different proportions. For instance, all three types of ET isoform mRNAs are present in human kidney and jejunum. Yet, in the central nervous system, ET-1 is the major isoform, while ET-3 is detected only to some extent. The diverse and uneven distribution of ET isoforms suggests that ET has multiple functions not only in the cardiovascular system but also in the nonvascular system.
Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite
Authors: Blanka Sharma, Sara Fermanian, Matthew Gibson, Shimon Unterman, Daniel A. Herzka, Brett Cascio, Jeannine Coburn, Alexander Y. Hui, Norman Marcus, Garry E. Gold, Jennifer H. Elisseeff
Journal: Science Translational Medicine (2013)

Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel biomaterial and stimulation of adjacent cartilage tissue development by mesenchymal stem cells. For translation to the joint environment, a chondroitin sulfate adhesive was applied to covalently bond and adhere the hydrogel to cartilage and bone tissue in articular defects. After preclinical testing in a caprine model, a pilot clinical study was initiated where the biomaterials system was combined with standard microfracture surgery in 15 patients with focal cartilage defects on the medial femoral condyle. Control patients were treated with microfracture alone. Magnetic resonance imaging showed that treated patients achieved significantly higher levels of tissue fill compared to controls. Magnetic resonance spin-spin relaxation times (T(2)) showed decreasing water content and increased tissue organization over time. Treated patients had less pain compared with controls, whereas knee function [International Knee Documentation Committee (IKDC)] scores increased to similar levels between the groups over the 6 months evaluated. No major adverse events were observed over the study period. With further clinical testing, this practical biomaterials strategy has the potential to improve the treatment of articular cartilage defects.
Fasting Glucose, Obesity, and Coronary Artery Calcification in Community-Based People Without Diabetes
Authors: Martin K. Rutter, Joseph M. Massaro, Udo Hoffmann, Christopher J. O’Donnell, Caroline S. Fox
Journal: Diabetes Care (2012)

Our objective was to assess whether impaired fasting glucose (IFG) and obesity are independently related to coronary artery calcification (CAC) in a community-based population.
<i>PAX-6</i>IN DEVELOPMENT AND EVOLUTION
Authors: Patrick Callaerts, Georg Halder, Walter J. Gehring
Journal: Annual Review of Neuroscience (1997)

▪ Abstract Pax-6 is a member of the Pax gene class and encodes a protein containing a paired domain and a homeodomain. The molecular characterization of Pax-6 genes from species of different animal phyla and the analysis of Pax-6 function in the developing eyes and central nervous system of vertebrates, Drosophila melanogaster, and Caenorhabditis elegans suggest that Pax-6 homologues share conserved functions. In this review, we present recent data on the structural and functional characterization of Pax-6 homologues from species of different animal phyla. We discuss the implications of these findings for our understanding of the development and evolution of eyes and nervous systems.
Leukemia After Therapy With Alkylating Agents for Childhood Cancer2
Authors: Margaret A. Tucker, Anna T. Meadows, John D. Boice, Marilyn Stovall, Odile Oberlin, Betty J. Stone, Jillian Birch, P. A. Voûte, Robert N. Hoover, Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1987)

The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents.
P153 Measuring variation in decision making within lung cancer multidisciplinary team (MDT) meetings-a pilot study
Authors: J. W. Donaldson, M. Ellis, R. Rintoul, D. R. Baldwin
Journal: Thorax (2011)

<h3>Introduction</h3> MDT meetings are now an essential and integral part of lung cancer services but no formal measurement of the variability of decisions made by these teams has been studied. Variation in decision making may be an important factor influencing the UK-wide differences in lung cancer outcomes and survival.1 <h3>Aim</h3> The aim of this pilot study was to develop and trial a tool for measuring variation in decision making within MDTs. <h3>Method</h3> Seven anonymised clinical cases were provided for discussion with accompanying radiology and histology to 12 MDTs in two regional lung cancer networks. MDTs were asked to provide a comprehensive plan for further investigation (if necessary) and treatment for each case. They were encouraged to specify modality of treatment. Treatment decisions were compared across the participating MDTs and a simple scoring system devised to rate concordance. 10 MDTs provided enough data for analysis. Straight-forward cases were considered by the investigators to have only one clear preferred treatment. Complex cases were less clear cut and selected to pose more of a challenge to MDTs. Nevertheless, each of these cases had a pre-defined preferred treatment option. <h3>Results</h3> The three cases rated straight-forward produced good agreement between MDTs, (Abstract P153 table 1) for radical vs palliative treatment. More complex cases resulted in less agreement between MDTs. One case (number 5) was excluded from analysis as it was clearly too ambiguous for MDTs to properly assess. <h3>Conclusions</h3> We conclude this method to compare decision making by MDTs is a feasible tool. A roll-out is now planned to a further 50 MDTs to document more clearly the variation in decision making UK-wide. Even with this small sample of MDTs for just two Networks, complex cases clearly produce greater variation in the proportion of patients offered radical treatment.
Contribution of Nonohnologous Duplicated Genes to High Habitat Variability in Mammals
Authors: Satoshi C. Tamate, Masakado Kawata, Takashi Makino
Journal: Molecular Biology and Evolution (2014)

The mechanism by which genetic systems affect environmental adaptation is a focus of considerable attention in the fields of ecology, evolution, and conservation. However, the genomic characteristics that constrain adaptive evolution have remained unknown. A recent study showed that the proportion of duplicated genes in whole Drosophila genomes correlated with environmental variability within habitat, but it remains unclear whether the correlation is observed even in vertebrates whose genomes including a large number of duplicated genes generated by whole-genome duplication (WGD). Here, we focus on fully sequenced mammalian genomes that experienced WGD in early vertebrate lineages and show that the proportion of small-scale duplication (SSD) genes in the genome, but not that of WGD genes, is significantly correlated with habitat variability. Moreover, species with low habitat variability have a higher proportion of lost duplicated genes, particularly SSD genes, than those with high habitat variability. These results indicate that species that inhabit variable environments may maintain more SSD genes in their genomes and suggest that SSD genes are important for adapting to novel environments and surviving environmental changes. These insights may be applied to predicting invasive and endangered species.
CD4+ T Cells Reactive to Enteric Bacterial Antigens in Spontaneously Colitic C3H/HeJBir Mice: Increased T Helper Cell Type 1 Response and Ability to Transfer Disease
Authors: Yingzi Cong, Steven L. Brandwein, Robert P. McCabe, A. Lazenby, Edward H. Birkenmeier, John P. Sundberg, Charles O. Elson
Journal: The Journal of Experimental Medicine (1998)

C3H/HeJBir mice are a new substrain that spontaneously develop colitis early in life. This study was done to determine the T cell reactivity of C3H/HeJBir mice to candidate antigens that might be involved in their disease. C3H/HeJBir CD4+ T cells were strongly reactive to antigens of the enteric bacterial flora, but not to epithelial or food antigens. The stimulatory material in the enteric bacteria was trypsin sensitive and restricted by class II major histocompatibility complex molecules, but did not have the properties of a superantigen. The precursor frequency of interleuken (IL)-2–producing, bacterial-reactive CD4+ T cells in colitic mice was 1 out of 2,000 compared to 1 out of 20,000–25,000 in noncolitic control mice. These T cells produced predominately IL-2 and interferon γ, consistent with a T helper type 1 cell response and were present at 3–4 wk, the age of onset of the colitis. Adoptive transfer of bacterial-antigen–activated CD4+ T cells from colitic C3H/HeJBir but not from control C3H/HeJ mice into C3H/HeSnJ scid/scid recipients induced colitis. These data represent a direct demonstration that T cells reactive with conventional antigens of the enteric bacterial flora can mediate chronic inflammatory bowel disease.
Serum factor from patients with cirrhosis and hepatocellular carcinoma enhances production of prostaglandin E2 by U937 cells
Authors: Hiroaki Iwamoto, Shigeru Sakamoto, Hajime Nawata
Journal: Hepatology (1991)

The effect of serum from patients with cirrhosis and hepatocellular carcinoma on the release of prostaglandin E2 by the human histiocytic lymphoma cell line U937 was investigated to explain the mechanism underlying the immunoregulatory dysfunction of monocytes in cirrhosis and hepatocellular carcinoma. Prostaglandin E2 production by U937 cells cultured with serum from cirrhosis patients (5.9 +/- 2.7 ng/ml, p less than 0.01) and hepatocellular carcinoma patients (5.4 +/- 2.6 ng/ml, p less than 0.01) was significantly higher than that of control cultures (2.0 +/- 1.0 ng/ml). This activity was decreased after heating and after freezing and thawing. By size exclusion fast protein liquid chromatography, the probable factor was eluted in the fraction with a molecular weight of 150 kD. By anion exchange chromatography with a stepwise increase of the NaCl concentration, the peak activity augmenting prostaglandin E2 production by U937 cells was eluted in the 0.05 to 0.1 mol/L NaCl fraction. The high level of this factor (monocyte-regulating factor) in patient serum might be one cause of abnormal monocyte immunoregulatory function in cirrhosis and hepatocellular carcinoma.
Housekeeping Genes for Phylogenetic Analysis of Eutherian Relationships
Authors: Morgan Kullberg, Maria A. Nilsson, Ulfur Arnason, Eric H. Harley, Axel Janke
Journal: Molecular Biology and Evolution (2006)

The molecular relationship of placental mammals has attracted great interest in recent years. However, 2 crucial and conflicting hypotheses remain, one with respect to the position of the root of the eutherian tree and the other the relationship between the orders Rodentia, Lagomorpha (rabbits, hares), and Primates. Although most mitochondrial (mt) analyses have suggested that rodents have a basal position in the eutherian tree, some nuclear data in combination with mt-rRNA genes have placed the root on the so-called African clade or on a branch that includes this clade and the Xenarthra (e.g., anteater and armadillo). In order to generate a new and independent set of molecular data for phylogenetic analysis, we have established cDNA sequences from different tissues of various mammalian species. With this in mind, we have identified and sequenced 8 housekeeping genes with moderately fast rate of evolution from 22 placental mammals, representing 11 orders. In order to determine the root of the eutherian tree, the same genes were also sequenced for 3 marsupial species, which were used as outgroup. Inconsistent with the analyses of nuclear + mt-rRNA gene data, the current data set did not favor a basal position of the African clade or Xenarthra in the eutherian tree. Similarly, by joining rodents and lagomorphs on the same basal branch (Glires hypothesis), the data set is also inconsistent with the tree commonly favored in mtDNA analyses. The analyses of the currently established sequences have helped examination of problematic parts in the eutherian tree at the same time as they caution against suggestions that have claimed that basal eutherian relationships have been conclusively settled.
Parthenolide, a Natural Inhibitor of Nuclear Factor-κB, Inhibits Lung Colonization of Murine Osteosarcoma Cells
Authors: Yuki Kishida, Hideki Yoshikawa, Akira Myoui
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The transcription factor nuclear factor-κB (NF-κB) regulates the expression of several genes important for tumor metastasis and is constitutively active in the highly metastatic murine osteosarcoma cell line LM8. Parthenolide, a sesquiterpene lactone, was reported to inhibit the DNA binding of NF-κB. The purpose of this study is to investigate the usefulness of parthenolide as target for antimetastatic therapies. Experimental Design: We examined the effect of parthenolide on metastasis-associated phenotypes in vitro and in murine experimental lung metastasis models by s.c. and i.v. inoculation of LM8 cells. Results: We found that parthenolide strongly induced apoptosis and inhibited cell proliferation and the expression of vascular endothelial growth factor in vitro. In the in vivo metastasis models, parthenolide treatment suppressed lung metastasis when treatment was initiated concurrently with s.c. or i.v. inoculation of tumor cells, whereas lung metastasis was not reduced when parthenolide was given after the homing of tumor cells. The growth of s.c. tumors that developed at the inoculation site was not suppressed by parthenolide. We also found that the genetic inhibition of NF-κB activity by expressing mutant IκBα suppressed lung metastasis in vivo but not s.c. tumor growth. This supports our notion that the metastasis-preventing effect of parthenolide is mediated at least in part by inhibition of NF-κB activity. Conclusions: These findings suggested that NF-κB is a potential molecular target for designing specific prophylactic interventions against distant metastasis and that parthenolide is a hopeful candidate for an antimetastatic drug.
What Is the Best Strategy for Reducing Deaths from Heart Disease?
Authors: Michael E Makover, Shah Ebrahim
Journal: PLoS Medicine (2005)

Coronary artery disease is a major cause of death worldwide. Two very different approaches have been proposed as a way of reducing these deaths. The “high risk” approach uses tools such as risk factor scoring and carotid ultrasound to try and identify those at highest risk, and then treats them aggressively. The “population” approach aims to shift the distribution of risk factors across a population in a beneficial direction with the goal of reducing heart disease in the whole population.
Transforming growth factor beta abrogates the effects of hematopoietins on eosinophils and induces their apoptosis.
Authors: R Alam, P Forsythe, S Stafford, Y Fukuda
Journal: The Journal of Experimental Medicine (1994)

Hematopoietins, interleukin (IL)-3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) have previously been shown to prolong eosinophil survival and abrogate apoptosis. The objective of this study was to investigate the effect of transforming growth factor beta (TGF-beta) on eosinophil survival and apoptosis. Eosinophils from peripheral blood of mildly eosinophilic donors were isolated to &amp;gt; 97% purity using discontinuous Percoll density gradient. Eosinophils were cultured with hematopoietins with or without TGF-beta for 4 d and their viability was assessed. We confirmed previous observations that hematopoietins prolonged eosinophil survival and inhibited apoptosis. TGF-beta at concentrations &amp;gt; or = 10(-12) M abrogated the survival-prolonging effects of hematopoietins in a dose-dependent manner and induced apoptosis as determined by DNA fragmentation in agarose gels. The effect of TGF-beta was blocked by an anti-TGF-beta antibody. The anti-TGF-beta antibody also prolonged eosinophil survival on its own. The culture of eosinophils with IL-3 and GM-CSF stimulated the synthesis of GM-CSF and IL-5, respectively, suggesting an autocrine mechanism of growth factor production. TGF-beta inhibited the synthesis of GM-CSF and IL-5 by eosinophils. TGF-beta did not have any effect on the expression of GM-CSF receptors on eosinophils. We also studied the effect of TGF-beta on eosinophil function and found that TGF-beta inhibited the release of eosinophil peroxidase. Thus, TGF-beta seems to inhibit eosinophil survival and function. The inhibition of endogenous synthesis of hematopoietins may be one mechanism by which TGF-beta blocks eosinophil survival and induces apoptosis.
Development of the ductus arteriosus in right ventricular outflow tract obstruction.
Authors: M A Santos, J N Moll, C Drumond, W B Araujo, N Romao, N B Reis
Journal: Circulation (1980)

We studied the morphology of the ductus arteriosus in 14 infants, ages 2--90 days. Eight (group 1) had pulmonary atresia (structural and functional) with an intact interventricular septum; six (group 2) had pulmonary atresia with a ventricular septal defect. The inferior angle of the ductus arteriosus at the aortic junction was measured in each patient. In group 1, this angle was obtuse in all but one patient. In group 2, the angle was acute in all. Further study of intracardiac anatomy suggested that in group 1, the obtuse inferior angle of the ductus arteriosus was the result of a late and progressive obstructive phenomenon that allowed normal right-to-left flow through the ductus arteriosus during much of fetal life. In group 2, the direction of ductus arteriosus flow (normally from the pulmonary trunk to the aorta) was reversed, and flowed from the aorta to the pulmonary trunk. This reversal of flow was probably of early onset in the fetus, the aorta receiving the total combined ventricular output, and produced a small ductus arteriosus with an acute inferior angle. It is extremely important not to rule out pulmonary atresia with an intact interventricular septum when aortography in the newborn shows a normal-sized ductus arteriosus with an obtuse inferior angle. Despite existing pulmonary atresia, these patients have neither a hypoplastic right ventricle nor discontinuity of the right ventricle with the pulmonary artery.