tbuckley/cabot-search huggingface dataset:
Drawing the tree of eukaryotic life based on the analysis of 2,269 manually annotated myosins from 328 species
Authors: Florian Odronitz, Martin Kollmar
Journal: Genome biology (2007)

The evolutionary history of organisms is expressed in phylogenetic trees. The most widely used phylogenetic trees describing the evolution of all organisms have been constructed based on single-gene phylogenies that, however, often produce conflicting results. Incongruence between phylogenetic trees can result from the violation of the orthology assumption and stochastic and systematic errors.Here, we have reconstructed the tree of eukaryotic life based on the analysis of 2,269 myosin motor domains from 328 organisms. All sequences were manually annotated and verified, and were grouped into 35 myosin classes, of which 16 have not been proposed previously. The resultant phylogenetic tree confirms some accepted relationships of major taxa and resolves disputed and preliminary classifications. We place the Viridiplantae after the separation of Euglenozoa, Alveolata, and Stramenopiles, we suggest a monophyletic origin of Entamoebidae, Acanthamoebidae, and Dictyosteliida, and provide evidence for the asynchronous evolution of the Mammalia and Fungi.Our analysis of the myosins allowed combining phylogenetic information derived from class-specific trees with the information of myosin class evolution and distribution. This approach is expected to result in superior accuracy compared to single-gene or phylogenomic analyses because the orthology problem is resolved and a strong determinant not depending on any technical uncertainties is incorporated, the class distribution. Combining our analysis of the myosins with high quality analyses of other protein families, for example, that of the kinesins, could help in resolving still questionable dependencies at the origin of eukaryotic life.
Pathogenesis of Arrhythmias in a Model of CKD
Authors: Chia-Hsiang Hsueh, Neal X. Chen, Shien-Fong Lin, Peng-Sheng Chen, Vincent H. Gattone, Matthew R. Allen, Michael C. Fishbein, Sharon M. Moe
Journal: Journal of the American Society of Nephrology (2014)

Patients with CKD have an increased risk of cardiovascular mortality from arrhythmias and sudden cardiac death. We used a rat model of CKD (Cy/+) to study potential mechanisms of increased ventricular arrhythmias. Rats with CKD showed normal ejection fraction but hypertrophic myocardium. Premature ventricular complexes occurred more frequently in CKD rats than normal rats (42% versus 11%, P=0.18). By optical mapping techniques, action potential duration (APD) at 80% of repolarization was longer in CKD rats (78±4ms) than normal rats (63±3 ms, P<0.05) at a 200-ms pacing cycle length. Calcium transient (CaT) duration was comparable. Pacing cycle length thresholds to induce CaT alternans or APD alternans were longer in CKD rats than normal rats (100±7 versus 80±3 ms and 93±6 versus 76±4 ms for CaT and APD alternans, respectively, P<0.05), suggesting increased vulnerability to ventricular arrhythmia. Ventricular fibrillation was induced in 9 of 12 CKD rats and 2 of 9 normal rats (P<0.05); early afterdepolarization occurred in two CKD rats but not normal rats. The mRNA levels of TGF-β, microRNA-21, and sodium calcium-exchanger type 1 were upregulated, whereas the levels of microRNA-29, L-type calcium channel, sarco/endoplasmic reticulum calcium-ATPase type 2a, Kv1.4, and Kv4.3 were downregulated in CKD rats. Cardiac fibrosis was mild and not different between groups. We conclude that cardiac ion channel and calcium handling are abnormal in CKD rats, leading to increased vulnerability to early afterdepolarization, triggered activity, and ventricular arrhythmias.
Maternal and Fetal Outcomes if Gestational Impaired Glucose Tolerance Is Not Treated
Authors: Ingrid Östlund, Ulf Hanson, Anders Björklund, Ragnhild Hjertberg, Nord Eva, Elisabeth Nordlander, Swahn Marja-Liisa, Jan Wager
Journal: Diabetes Care (2003)

OBJECTIVE—To evaluate whether there is increased maternal or neonatal morbidity in connection with impaired glucose tolerance (IGT) during pregnancy when the condition is not treated. RESEARCH DESIGN AND METHODS—During the study period of 1997–2001, in a defined geographical area in Sweden, the diagnostic criteria for gestational diabetes mellitus (GDM) were limited to the criteria for diabetes. Prospectively, 213 women who were identified with IGT during pregnancy were undiagnosed and untreated. Data on maternal and fetal outcome was collected from records. For each case subject, four control subjects were taken from the same delivery department. RESULTS—The proportion of women who underwent cesarean section was significantly higher in the case subjects than in the control subjects and was independently associated with IGT. The adjusted odds ratio (OR) was 1.9 (95% CI 1.2–2.9). The proportion of infants who were large for gestational age (LGA), defined as birth weight &amp;gt;2 SDs greater than the mean for gestation and sex, was independently significantly associated with untreated IGT during pregnancy (OR 7.3, 95% CI 4.1–12.7). Admission to a neonatal intensive care unit (NICU) for 2 days or longer was more common (adjusted OR 2.0, 95% CI 1.1–3.8). However, 71.3% of the children in the IGT group and 87.3% of the control subjects had no neonatal complications. CONCLUSIONS—There is increased independent association between cesarean section rate, prematurity, LGA, and macrosomic infants born to mothers with untreated IGT. Most of the children were healthy, but there is still increased morbidity. Therefore, to evaluate the effects of treatment, there is a need for a randomized study.
First Application of the SINE (Short Interspersed Repetitive Element) Method to Infer Phylogenetic Relationships in Reptiles: An Example from the Turtle Superfamily Testudinoidea
Authors: Takeshi Sasaki, Kazuhiko Takahashi, Masato Nikaido, Seiko Miura, Yuichirou Yasukawa, Norihiro Okada
Journal: Molecular Biology and Evolution (2004)

Although turtles (order Testudines) constitute one of the major reptile groups, their phylogenetic relationships remain largely unresolved. Hence, we attempted to elucidate their phylogeny using the SINE (short interspersed repetitive element) method, in which the sharing of a SINE at orthologous loci is indicative of synapomorphy. First, a detailed characterization of the tortoise polIII/SINE was conducted using 10 species from eight families of hidden-necked turtles (suborder Cryptodira). Our analysis of 382 SINE sequences newly isolated in the present study revealed two subgroups, namely Cry I and Cry II, which were distinguishable according to diagnostic nucleotides in the 3' region. Furthermore, four (IA-ID) and five (IIA-IIE) different SINE types were identified within Cry I and Cry II subgroups, respectively, based on features of insertions/deletions located in the middle of the SINE sequences. The relative frequency of occurrence of the subgroups and the types of SINEs in this family were highly variable among different lineages of turtles, suggesting active differential retroposition in each lineage. Further application of the SINE method using the most retrotranspositionally active types, namely IB and IC, challenged the established phylogenetic relationships of Bataguridae and its related families. The data for 11 orthologous loci demonstrated a close relationship between Bataguridae and Testudinidae, as well as the presence of the three clades within Bataguridae. Although the SINE method has been used to infer the phylogenies of a number of vertebrate groups, it has never been applied to reptiles. The present study represents the first application of this method to a phylogenetic analysis of this class of vertebrates, and it provides detailed information on the SINE subgroups and types. This information may be applied to the phylogenetic resolution of relevant turtle lineages.
Transduction of Hepatocytes after Neonatal Delivery of a Moloney Murine Leukemia Virus Based Retroviral Vector Results in Long-Term Expression of β-Glucuronidase in Mucopolysaccharidosis VII Dogs
Authors: Lingfei Xu, Mark E. Haskins, John R. Melniczek, Cuihua Gao, Margaret A. Weil, Thomas M. O'Malley, Patricia A. O'Donnell, Hamutal Mazrier, N. Matthew Ellinwood, Jean Zweigle, John H. Wolfe, Katherine Parker Ponder
Journal: Molecular Therapy (2002)

The use of Moloney murine leukemia virus (MLV)-based retroviral vectors (RV) can result in stable in vivo expression in the liver, but these vectors only transduce replicating hepatocytes. As newborn animals exhibit rapid growth, we evaluated the ability of MLV-based RV to transduce hepatocytes in neonatal dogs. IV injection of a β-galactosidase-expressing RV at 3 days after birth resulted in transduction of 9% of hepatocytes. Prior treatment with human hepatocyte growth factor at 2.5 mg/kg did not increase transduction. Although cells from the spleen were also transduced with moderate efficiency, cells from other organs were not. Neonatal dogs with mucopolysaccharidosis VII (MPS VII) received an IV injection of an RV containing the canine β-glucuronidase (cGUSB) cDNA. At several months after transduction, clusters of hepatocytes that expressed high levels of cGUSB were present in the liver, which probably derived from replication of transduced hepatocytes. At 6 months after transduction, serum GUSB levels were 73% that of homozygous normal dogs and were 34% of the peak values observed at 1 week. We conclude that neonatal delivery of an MLV-based RV results in stable transduction of hepatocytes in dogs. This approach could result in immediate correction in patients with an otherwise-lethal genetic deficiency. The use of Moloney murine leukemia virus (MLV)-based retroviral vectors (RV) can result in stable in vivo expression in the liver, but these vectors only transduce replicating hepatocytes. As newborn animals exhibit rapid growth, we evaluated the ability of MLV-based RV to transduce hepatocytes in neonatal dogs. IV injection of a β-galactosidase-expressing RV at 3 days after birth resulted in transduction of 9% of hepatocytes. Prior treatment with human hepatocyte growth factor at 2.5 mg/kg did not increase transduction. Although cells from the spleen were also transduced with moderate efficiency, cells from other organs were not. Neonatal dogs with mucopolysaccharidosis VII (MPS VII) received an IV injection of an RV containing the canine β-glucuronidase (cGUSB) cDNA. At several months after transduction, clusters of hepatocytes that expressed high levels of cGUSB were present in the liver, which probably derived from replication of transduced hepatocytes. At 6 months after transduction, serum GUSB levels were 73% that of homozygous normal dogs and were 34% of the peak values observed at 1 week. We conclude that neonatal delivery of an MLV-based RV results in stable transduction of hepatocytes in dogs. This approach could result in immediate correction in patients with an otherwise-lethal genetic deficiency.
Mast cells and immunoglobulin E in inflammatory bowel disease.
Authors: G Lloyd, F H Green, H Fox, V Mani, L A Turnberg
Journal: Gut (1975)

The numbers of mast cells and of IgE-containing immunocytes in the bowel wall of patients suffering from Crohn's disease of ulcerative colitis have been estimated and the results compared with those found in normal control specimens. In ulcerative colitis there is a slight rise in the number of mast cells and it appears that these participate in the inflammatory process in a non-specific manner; the number of IgE-containing immunocytes is not significantly altered. In Crohn's disease there is an almost total absence of stainable mast cells in affected areas of the bowel, together with a marked decrease in IgE-containing immunocytes. It is suggested that these findings are due to degranulation of mast cells and consumption of IgE as a result of an immediate hypersensitivity reaction in the bowel wall, this being one component of the protein inflammatory and immunological response to the entry of a variety of antigenic material.
Conservation of alternative splicing and genomic organization of the myosin alkali light-chain (Mlc1) gene among Drosophila species.
Authors: B G Leicht, E M Lyckegaard, C M Benedict, A G Clark
Journal: Molecular Biology and Evolution (1993)

The Mlc1 gene of Drosophila melanogaster encodes two MLC1 isoforms via developmentally regulated alternative pre-mRNA splicing. In larval muscle and tubular and abdominal muscles of adults, all of the six exons are included in the spliced mRNA, whereas, in the fibrillar indirect flight muscle of adult, exon 5 is excluded from the mRNA. We show that this tissue-specific pattern of alternative splicing of the Mlc1 pre-mRNA is conserved in D. simulans, D. pseudoobscura, and D. virilis. Isolation and sequencing of the Mlc1 genes from these three other Drosophila species have revealed that the overall organization of the genes is identical and that the genes have maintained a very high level of sequence identity within the coding region. Pairwise amino acid identities are 94%-99%, and there are no charge changes among the proteins. Total nucleotide divergence within the coding region of the four genes supports the accepted genealogy of these species, but the data indicate a significantly higher rate of amino acid replacement in the branch leading to D. pseudoobscura. A comparison of nucleotide substitutions in the coding portions of exon 5 and exon 6, which encode the alternative carboxyl termini of the two MLC1 isoforms, suggests that exon 5 is subject to greater evolutionary constraints than is exon 6. In addition to the coding sequences, there is significant sequence conservation within the 5' and 3' noncoding DNA and two of the introns, including one that flanks exon 5. These regions are candidates for cis-regulatory elements. Our results suggest that evolutionary constraints are acting on both the coding and noncoding sequences of the Mlc1 gene to maintain proper expression and function of the two MLC1 polypeptides.
Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation
Authors: Jie Huang, Maria Sabater-Lleal, Folkert W. Asselbergs, David Tregouet, So-Youn Shin, Jingzhong Ding, Jens Baumert, Tiphaine Oudot-Mellakh, Lasse Folkersen, Andrew D. Johnson, Nicholas L. Smith, Scott M. Williams, Mohammad A. Ikram, Marcus E. Kleber, Diane M. Becker, Vinh Truong, Josyf C. Mychaleckyj, Weihong Tang, Qiong Yang, Bengt Sennblad, Jason H. Moore, Frances M. K. Williams, Abbas Dehghan, Günther Silbernagel, Elisabeth M. C. Schrijvers, Shelly Smith, Mahir Karakas, Geoffrey H. Tofler, Angela Silveira, Gerjan J. Navis, Kurt Lohman, Ming-Huei Chen, Annette Peters, Anuj Goel, Jemma C. Hopewell, John C. Chambers, Danish Saleheen, Per Lundmark, Bruce M. Psaty, Rona J. Strawbridge, Bernhard O. Boehm, Angela M. Carter, Christa Meisinger, John F. Peden, Joshua C. Bis, Barbara McKnight, John Öhrvik, Kent Taylor, Maria Grazia Franzosi, Udo Seedorf, Rory Collins, Anders Franco-Cereceda, Ann-Christine Syvänen, Alison H. Goodall, Lisa R. Yanek, Mary Cushman, Martina Müller-Nurasyid, Aaron R. Folsom, Saonli Basu, Nena Matijevic, Wiek H. van Gilst, Jaspal S. Kooner, Albert Hofman, John Danesh, Robert Clarke, James B. Meigs, Sekar Kathiresan, Muredach P. Reilly, Norman Klopp, Tamara B. Harris, Bernhard R. Winkelmann, Peter J. Grant, Hans L. Hillege, Hugh Watkins, Timothy D. Spector, Lewis C. Becker, Russell P. Tracy, Winfried März, Andre G. Uitterlinden, Per Eriksson, Francois Cambien, Pierre-Emmanuel Morange, Wolfgang Koenig, Nicole Soranzo, Pim van der Harst, Yongmei Liu, Christopher J. O'Donnell, Anders Hamsten
Journal: Blood (2012)
The CC Chemokine Receptor 4 as a Novel Specific Molecular Target for Immunotherapy in Adult T-Cell Leukemia/Lymphoma
Authors: Takashi Ishida, Shinsuke Iida, Yoshiki Akatsuka, Toshihiko Ishii, Mikinori Miyazaki, Hirokazu Komatsu, Hiroshi Inagaki, Noriko Okada, Teizo Fujita, Kenya Shitara, Shiro Akinaga, Toshitada Takahashi, Atae Utsunomiya, Ryuzo Ueda
Journal: Clinical Cancer Research (2004)

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with dismal prognosis, and no optimal therapy has been developed. We tested the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, KM2760, to develop a novel immunotherapy for this refractory tumor. In the presence of peripheral blood mononuclear cells (PBMCs) from healthy adult donors, KM2760 induced CCR4-specific antibody-dependent cellular cytotoxicity (ADCC) against CCR4-positive ATLL cell lines and primary tumor cells obtained from ATLL patients. We next examined the KM2760-induced ADCC against primary ATLL cells in an autologous setting. Antibody-dependent cellular cytotoxicity mediated by autologous effector cells was generally lower than that mediated by allogeneic control effector cells. However, a robust ADCC activity was induced in some cases, which was comparable with that mediated by allogeneic effector cells. It suggests that the ATLL patients' PBMCs retain substantial ADCC-effector function, although the optimal conditions for maximal effect have not yet been determined. In addition, we also found a high expression of FoxP3 mRNA and protein, a hallmark of regulatory T cells, in ATLL cells, indicating the possibility that ATLL cells originated from regulatory T cells. KM2760 reduced FoxP3 mRNA expression in normal PBMCs along with CCR4 mRNA by lysis of CCR4+ T cells in vitro. Our data suggest not only that the CCR4 molecule could be a suitable target for the novel antibody-based therapy for patients with ATLL but also that KM2760 may induce effective tumor immunity by reducing the number of regulatory T cells.
Different localization of two types of endothelin receptor mRNA in microdissected rat nephron segments using reverse transcription and polymerase chain reaction assay.
Authors: Y Terada, K Tomita, H Nonoguchi, F Marumo
Journal: Journal of Clinical Investigation (1992)

Recent studies have revealed that endothelins (ETs) have at least two types of receptors. One receptor has high affinity to ET-1 and ET-2 and low affinity to ET-3 (A type). The other receptor binds almost equally to ET-1, ET-2, and ET-3 (B type). In this study, microlocalization of mRNA coding for the A-type and B-type ET receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction assay of individual microdissected renal tubule segments along the nephron, glomeruli, vasa recta bundle, and arcuate arteries. Large signals for the B-type receptor polymerase chain reaction product were detected in the initial and terminal inner medullary collecting duct and the glomerulus, while small signals were found in the cortical collecting duct and outer medullary collecting duct, vasa recta bundle, and arcuate artery. In contrast, A-type receptor mRNA was detected only in the glomerulus, vasa recta bundle, and arcuate artery. Thus, the two ET receptor subtypes are distributed differently along the nephron. This suggests that the two types of receptors and ET families may affect kidney functioning in different ways.
BRAIN DAMAGE FROM CHRONIC ALCOHOLISM: THE DIAGNOSIS OF INTERMEDIATE STAGE OF ALCOHOLIC BRAIN DISEASE
Authors: A. E. BENNETT, G. L. MOWERY, JOEL T. FORT
Journal: American Journal of Psychiatry (1960)

This study indicates the presence of a syndrome of an intermediate stage of alcoholic brain disease, midway between the acute and the chronic stages. In the intermediate stage the EEG changes, the clinical findings and the psychological test data lead to the diagnosis of incipient brain damage; the presence of cerebral atrophy can be confirmed by pneumogram. The study of 227 cases showed 98 in the acute stage, 81 in the intermediate stage, and 48 in the chronic stage. In the 81 patients in the intermediate stage, 64 (79%) had abnormal EEG records, with organic brain damage indicated in 9 cases by psychological tests or pneumograms or both. The implications for treatment are summarized: 1. The persistence of abnormal EEG records after the acute episode emphasizes the need for comprehensive medical treatment of the organic factors, before the brain damage becomes irreversible. These organic factors are often erroneously considered to indicate personality disorders, with consequent ineffective therapeutic measures. 2. The patient under institutional or other supervisory control must stop all use of alcohol. 3. After improvement of the organic features, the patient is ready to begin individual and group psychotherapy and a general rehabilitative program, including the help of Alcoholics Anonymous and similar organizations. 4. The relatives must be made to understand the seriousness of the disease, and their cooperation enlisted in the treatment program. 5. The problem of alcoholic addiction must eventually be attacked at a national level with steps to insure early detection of addiction and organic brain disease, and with a broad program of control of drinking and of rehabilitation.
A biliary HCO<sub>3</sub><sup>−</sup>umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes
Authors: Simon Hohenester, Lucas Maillette de Buy Wenniger, Coen C. Paulusma, Sandra J. van Vliet, Douglas M. Jefferson, Ronald P. Oude Elferink, Ulrich Beuers
Journal: Hepatology (2011)

Human cholangiocytes are continuously exposed to millimolar levels of hydrophobic bile salt monomers. We recently hypothesized that an apical biliary HCO Symbol umbrella might prevent the protonation of biliary glycine–conjugated bile salts and uncontrolled cell entry of the corresponding bile acids, and that defects in this biliary HCO Symbol umbrella might predispose to chronic cholangiopathies. Here, we tested in vitro whether human cholangiocyte integrity in the presence of millimolar bile salt monomers is dependent on (1) pH, (2) adequate expression of the key HCO Symbol exporter, anion exchanger 2 (AE2), and (3) an intact cholangiocyte glycocalyx. To address these questions, human immortalized cholangiocytes and cholangiocarcinoma cells were exposed to chenodeoxycholate and its glycine/taurine conjugates at different pH levels. Bile acid uptake was determined radiochemically. Cell viability and apoptosis were measured enzymatically. AE2 was knocked down by lentiviral short hairpin RNA. A cholangiocyte glycocalyx was identified by electron microscopy, was enzymatically desialylated, and sialylation was quantified by flow cytometry. We found that bile acid uptake and toxicity in human immortalized cholangiocytes and cholangiocarcinoma cell lines in vitro were pH and AE2 dependent, with the highest rates at low pH and when AE2 expression was defective. An apical glycocalyx was identified on cholangiocytes in vitro by electron microscopic techniques. Desialylation of this protective layer increased cholangiocellular vulnerability in a pH–dependent manner. Conclusion: A biliary HCO Symbol umbrella protects human cholangiocytes against damage by bile acid monomers. An intact glycocalyx and adequate AE2 expression are crucial in this process. Defects of the biliary HCO Symbol umbrella may lead to the development of chronic cholangiopathies. (Hepatology 2012;55:173–183)