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1.
Dis Aquat Organ ; 127(3): 163-175, 2018 03 05.
Article in English | MEDLINE | ID: mdl-29516856

ABSTRACT

The giant (>3 m) parasitic nematode Crassicauda magna infects kogiid whales, although only 3 studies to date have provided detailed descriptions of these worms, all based upon fragmented specimens. These fragments were found within the neck region of kogiids, an unusual anatomic site for this genus of parasites. C. magna is a species-specific parasite among kogiids, infecting only pygmy sperm whales Kogia breviceps, and with a primarily cervico-thoracic distribution. To date, however, the pattern of habitat use within the host and transmission path of this parasite remain unknown. We used detailed dissections (n = 12), histological examination of host tissues (n = 2), and scanning electron microscopy of excised nematodes (n = 7) to enhance our understanding of this host-parasite relationship. Results revealed that a critical habitat for the parasite is an exocrine gland in the whale's ventral cervical region. C. magna male and female tails were found intertwined within the glandular lumen, and eggs were observed within its presumed secretion, illuminating the transmission path out of the host. The cephalic ends of these worms were often meters away (curvilinearly), embedded deeply within epaxial muscle. A single worm's complete, tortuous 312 cm course, from the gland to its termination in the contralateral epaxial muscle, is described for the first time. This study also provides the first scanning electron micrographs of C. magna, which illustrate taxonomically important features of the heads and tails of both male and female worms.


Subject(s)
Spirurida Infections/veterinary , Spirurida/classification , Spirurida/physiology , Whales/parasitology , Animals , Exocrine Glands/parasitology , Female , Male , Neck/parasitology , Spirurida Infections/parasitology , Spirurida Infections/pathology
2.
J R Army Med Corps ; 164(5): 332-334, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29643121

ABSTRACT

INTRODUCTION: Focused assessment with sonography in trauma (FAST) is historically an effective method of assessing the patient in the trauma bay in order to aid decision-making and optimise patient outcomes. However, in the UK civilian practice, the use of FAST may decline given a recent change in National Institute for Health and Care Excellence guidance as a result of improvement in CT availability and resuscitation techniques. METHOD: In the Role 3 Medical Treatment Facility, Camp Bastion, 187 patients with trauma who received FAST in the trauma bay in 2014 were reviewed to determine the accuracy of FAST in the deployed environment. RESULTS: The data demonstrates the sensitivity and specificity of FAST to be 75% and 99.3%, respectively. CONCLUSIONS: This study demonstrates that FAST is accurate on operations. FAST is provided by the integrated radiologist as part of damage control radiology, which gives the team leader rapid diagnostic information to improve decision-making and ultimately patient outcomes. CT is heavily utilised in civilian practice; however, the military operates in a different environment often with multiple casualties and limited access to CT, as a result, portable ultrasound will continue to be a valuable tool on operations if used properly. The next challenge is to develop and maintain this high diagnostic accuracy in future deployments where the memories of our prior success may fade.


Subject(s)
Military Medicine , Point-of-Care Systems , Wounds and Injuries/diagnostic imaging , Humans , Military Personnel , Sensitivity and Specificity , Triage , Ultrasonography , United Kingdom , Warfare
3.
Anaesthesia ; 72(8): 987-992, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28463474

ABSTRACT

Emergency cricothyrotomy is a common feature in all difficult airway algorithms. It is the final step following a 'can't intubate, can't oxygenate' scenario. It is rarely performed and has a significant failure rate. There is variation in the reported size of the cricothyroid membrane, especially across population groups. Procedural failure may result from attempting to pass a device with too large an external diameter through the cricothyroid membrane. We aimed to determine the maximum height of the cricothyroid membrane in a UK trauma population. Electronic callipers were used to measure the maximum height of the cricothyroid membrane on 482 reformatted trauma computed tomography scans, 377 (78.2%) of which were in male patients. The mean (SD) height of the cricothyroid membrane, as independently measured by two radiologists, was 7.89 (2.21) mm and 7.88 (2.22) mm in male patients, and 6.00 (1.76) mm and 5.92 (1.71) mm in female patients. The presence of concurrent tracheal intubation or cervical spine immobilisation was found not to have a significant effect on cricothyroid membrane height. The cricothyroid membrane height in the study population was much smaller than that previously reported. Practitioners encountering patients who may require an emergency surgical airway should be aware of these data. Rescue airway equipment with variety of external diameters should be immediately available.


Subject(s)
Cricoid Cartilage/anatomy & histology , Intubation, Intratracheal/methods , Tomography, X-Ray Computed/methods , Wounds and Injuries/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Cricoid Cartilage/diagnostic imaging , Female , Humans , Male , Middle Aged , Wounds and Injuries/diagnostic imaging , Young Adult
4.
Phys Rev Lett ; 117(18): 182701, 2016 Oct 28.
Article in English | MEDLINE | ID: mdl-27835017

ABSTRACT

The ^{19}Ne(p,γ)^{20}Na reaction is the second step of a reaction chain which breaks out from the hot CNO cycle, following the ^{15}O(α,γ)^{19}Ne reaction at the onset of x-ray burst events. We investigate the spectrum of the lowest proton-unbound states in ^{20}Na in an effort to resolve contradictions in spin-parity assignments and extract reliable information about the thermal reaction rate. The proton-transfer reaction ^{19}Ne(d,n)^{20}Na is measured with a beam of the radioactive isotope ^{19}Ne at an energy around the Coulomb barrier and in inverse kinematics. We observe three proton resonances with the ^{19}Ne ground state, at 0.44, 0.66, and 0.82 MeV c.m. energies, which are assigned 3^{+}, 1^{+}, and (0^{+}), respectively. In addition, we identify two resonances with the first excited state in ^{19}Ne, one at 0.20 MeV and one, tentatively, at 0.54 MeV. These observations allow us for the first time to experimentally quantify the astrophysical reaction rate on an excited nuclear state. Our experiment shows an efficient path for thermal proton capture in ^{19}Ne(p,γ)^{20}Na, which proceeds through ground state and excited-state capture in almost equal parts and eliminates the possibility for this reaction to create a bottleneck in the breakout from the hot CNO cycle.

5.
Inorg Chem ; 53(6): 2787-96, 2014 Mar 17.
Article in English | MEDLINE | ID: mdl-24524249

ABSTRACT

The hydrothermal reaction of uranium trioxide and methylenediphosphonic acid in the presence of silver nitrate resulted in the formation of three new uranyl coordination polymers: AgUO2[CH2(PO3)(PO3H)] (Ag-1), [Ag2(H2O)1.5]{(UO2)2[CH2(PO3)2]F2}·(H2O)0.5 (Ag-2), and Ag2UO2[CH2(PO3)2] (Ag-3). All consist of uranyl pentagonal bipyramids that form two-dimensional layered structures. Ag-1 and Ag-3 possess the same structural building unit, but the structures are different; Ag-3 is formed through edge-sharing of F atoms to form UO5F2 dimers. The pH and silver cation have significant effects on the structure that is synthesized. Raman spectra of single crystals of Ag-1, Ag-2, and Ag-3 reveal v1 UO2(2+) symmetric stretches of 816 and 829, 822, and 802 cm(-1), respectively. Electronic structure calculations were performed using the projector augmented wave (PAW) method with density functional theory (DFT) to gain insight into the nature of bonding and electronic characteristics of the synthesized compounds. Herein, we report the syntheses, crystal structures, Raman spectroscopy, and luminescent behavior of these three compounds.

6.
Clin Radiol ; 69(4): 424-30, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24333001

ABSTRACT

Digital tomosynthesis is a radiographic technique that generates a number of coronal raw images of a patient from a single pass of the x-ray tube. Tomosynthesis provides some of the tomographic benefits of computed tomography (CT), but at a much lower dose of radiation and cost when compared to CT. This review illustrates the range of practical applications of digital tomosynthesis of the chest.


Subject(s)
Lung Neoplasms/diagnostic imaging , Lung/diagnostic imaging , Radiography, Thoracic , Tomography, X-Ray Computed , Adult , Female , Humans , Lung/pathology , Lung Neoplasms/pathology , Male , Middle Aged , Radiation Dosage , Radiographic Image Enhancement , Radiographic Image Interpretation, Computer-Assisted , Reproducibility of Results
7.
Clin Radiol ; 68(1): 82-4, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22832145

ABSTRACT

Penetrating eye injuries are uncommon in a civilian environment, but unfortunately, very common in a military emergency department. Ultrasound of the eye is quick, reliable, accurate, and easy to learn. This review aims to demonstrate normal anatomy and penetrating injuries of the anterior and posterior compartments of the eye.


Subject(s)
Eye Injuries, Penetrating/diagnostic imaging , Military Personnel , Afghan Campaign 2001- , Anterior Chamber/injuries , Eye Foreign Bodies/diagnostic imaging , Humans , Posterior Eye Segment/injuries , Ultrasonography
8.
J Comp Physiol B ; 192(5): 623-645, 2022 09.
Article in English | MEDLINE | ID: mdl-35779114

ABSTRACT

Adipose tissue has many important functions including metabolic energy storage, endocrine functions, thermoregulation and structural support. Given these varied functions, the microvascular characteristics within the tissue will have important roles in determining rates/limits of exchange of nutrients, waste, gases and molecular signaling molecules between adipose tissue and blood. Studies on skeletal muscle have suggested that tissues with higher aerobic capacity contain higher microvascular density (MVD) with lower diffusion distances (DD) than less aerobically active tissues. However, little is known about MVD in adipose tissue of most vertebrates; therefore, we measured microvascular characteristics (MVD, DD, diameter and branching) and cell size to explore the comparative aerobic activity in the adipose tissue across diving tetrapods, a group of animals facing additional physiological and metabolic stresses associated with diving. Adipose tissues of 33 animals were examined, including seabirds, sea turtles, pinnipeds, baleen whales and toothed whales. MVD and DD varied significantly (P < 0.001) among the groups, with seabirds generally having high MVD, low DD and small adipocytes. These characteristics suggest that microvessel arrangement in short duration divers (seabirds) reflects rapid lipid turnover, compared to longer duration divers (beaked whales) which have relatively lower MVD and greater DD, perhaps reflecting the requirement for tissue with lower metabolic activity, minimizing energetic costs during diving. Across all groups, predictable scaling patterns in MVD and DD such as those observed in skeletal muscle did not emerge, likely reflecting the fact that unlike skeletal muscle, adipose tissue performs many different functions in marine organisms, often within the same tissue compartment.


Subject(s)
Diving , Adipose Tissue/physiology , Animals , Body Temperature Regulation , Diving/physiology , Muscle, Skeletal , Whales
9.
Plant Dis ; 95(11): 1346-1357, 2011 Nov.
Article in English | MEDLINE | ID: mdl-30731790

ABSTRACT

Between 2005 and 2009, millions of U.S. and Canadian soybean acres that would have received fungicide application remained untreated for soybean rust due to information disseminated through the Integrated Pest Management Pest Information Platform for Extension and Education (ipmPIPE), increasing North American producers' profits by hundreds of millions of dollars each year. The results of our analysis of Phakopsora pachyrhizi urediniospores in rain collections, aerobiology model output, and observations of soybean rust spread in 2007 and 2008 show a strong correspondence between spore collections and model predictions for the continental interior of North America, where soybean is an important crop. The analysis suggests that control practices based on up-to-date maps of soybean rust observations and associated commentary from Extension Specialists delivered by the ipmPIPE may have suppressed the number and strength of inoculum source areas in the southern states and retarded the northward progress of seasonal soybean rust incursions into continental North America. The analysis further indicates that spore trapping and aerobiological modeling can reduce our reliance on the costly Sentinel Plot Network while maintaining the effectiveness of the ipmPIPE system for soybean rust management.

10.
J R Army Med Corps ; 157(3 Suppl 1): S289-92, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22049810

ABSTRACT

Damage Control Radiology describes the process where imaging aids the decision making process in a trauma setting and is an important part of Damage Control Surgery and Resuscitation. This article outlines how radiology fits in to the primary and secondary surveys and discusses the role of imaging modalities such as ultrasound and CT. The importance of deployed radiology to aid rapid diagnosis and decision making is described.


Subject(s)
Decision Making , Wounds and Injuries/diagnosis , Humans , Magnetic Resonance Imaging , Radiography, Interventional , Tomography, X-Ray Computed , Ultrasonography , Warfare , Wounds and Injuries/diagnostic imaging
11.
Nat Commun ; 12(1): 56, 2021 01 04.
Article in English | MEDLINE | ID: mdl-33397922

ABSTRACT

RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets. Deletion of these indicated that while TIAM1 deficiency could suppress Apc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation of Vav2, with subsequent targeting of all three (Vav2-/- Vav3-/- Tiam1-/-), profoundly suppressing hyperproliferation, tumourigenesis and RAC1 activity, without impacting normal homeostasis. Critically, the observed RAC-GEF dependency was negated by oncogenic KRAS mutation. Together, these data demonstrate that while targeting RAC-GEF molecules may have therapeutic impact at early stages, this benefit may be lost in late stage disease.


Subject(s)
Carcinogenesis/metabolism , Carcinogenesis/pathology , Guanine Nucleotide Exchange Factors/metabolism , Intestines/pathology , Signal Transduction , rac1 GTP-Binding Protein/metabolism , Adenomatous Polyposis Coli Protein/metabolism , Animals , Carcinogenesis/genetics , Homeostasis , Intestines/ultrastructure , Mice, Knockout , Mutation/genetics , Organ Specificity , Phenotype , Proto-Oncogene Proteins c-vav/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , T-Lymphoma Invasion and Metastasis-inducing Protein 1/metabolism , Up-Regulation , Wnt Signaling Pathway
12.
J Exp Med ; 177(4): 999-1008, 1993 Apr 01.
Article in English | MEDLINE | ID: mdl-8459227

ABSTRACT

To determine the fate of anti-DNA antibody-bearing B cells in normal mice, we generated transgenic mice bearing the heavy (H) and light (L) chain genes of a well-characterized anti-double-stranded DNA antibody. This antibody was originally isolated from a diseased MRL/lpr mouse and has characteristics common to spontaneously arising anti-DNA antibodies. Results show that the H/L transgene (tg) immunoglobulin receptor is not expressed by animals bearing both tgs, although single tg animals (H or L) express their transgenes. Young H/L tg animals express few B cells, whereas adult H/L tg animals maintain almost normal B cell numbers. Analysis of the immunoglobulin receptors used by adult B cells shows that all contain the tg H chain in association with endogenous L chains. These B cells transcribe the L tg as well as the rearranged endogenous L chain gene, and loss of endogenous L chain gene transcription results in resurrection of the 3H9 H/L tg product. Examination of the endogenous L chains used by these cells shows that they represent a highly restricted subset of V genes. Taken together, these data suggest that autoreactive transgenic B cells can rearrange endogenous L chain genes to alter surface receptors. Those L chains that compete successfully with the L tg for H chain binding, and that create a nonautoreactive receptor, allow the B cell to escape deletion. We suggest that this receptor editing is a mechanism used by immature autoreactive B cells to escape tolerance.


Subject(s)
Autoantibodies/immunology , B-Lymphocytes/immunology , Immune Tolerance , Receptors, Antigen, B-Cell/immunology , Animals , Autoantibodies/genetics , Base Sequence , Blotting, Southern , Cell Line , DNA/immunology , Flow Cytometry , Hybridomas , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/immunology , Immunoglobulin Heavy Chains/metabolism , Immunoglobulin Light Chains/genetics , Immunoglobulin Light Chains/immunology , Immunoglobulin Light Chains/metabolism , Mice , Mice, Inbred BALB C , Mice, Transgenic , Molecular Sequence Data , Receptors, Antigen, B-Cell/metabolism , Restriction Mapping
13.
Inorg Chem ; 49(7): 3337-42, 2010 Apr 05.
Article in English | MEDLINE | ID: mdl-20218728

ABSTRACT

The hydrothermal reaction of PuO(2) with CH(2)(PO(3)H(2))(2) results in the formation of alpha-Pu[CH(2)(PO(3))(2)](H(2)O), beta-Pu[CH(2)(PO(3))(2)](H(2)O) (1), gamma-Pu[CH(2)(PO(3))(2)](H(2)O) (2), and Pu[CH(2)(PO(3))(2)](H(2)O).H(2)O (3) as crystalline compounds with blue, green, red, and very pale peach coloration, respectively. In all cases single crystal X-ray diffraction studies reveals Pu(4+) coordinated by [CH(2)(PO(3))(2)](4-) and water to yield PuO(7) units. The methylenediphosphonate anions bridge between these units to yield three-dimensional networks. Bond-valence parameters of R(o) = 2.068 and b = 0.385 have been derived for Pu(4+) using a combination of the data reported in this work with that available in crystallographic databases. UV-vis-NIR spectroscopic measurements demonstrate that despite the dramatic color differences all of the compounds contain Pu(4+), and that subtle changes in the visible region of the spectra account for different colors.

14.
Inorg Chem ; 49(6): 2639-48, 2010 Mar 15.
Article in English | MEDLINE | ID: mdl-20166683

ABSTRACT

Three binuclear copper(II) complexes were characterized as solids by X-ray diffraction and in solution by UV/vis spectrophotometric titration, and subsequently evaluated for their glycosidase-like activity. The structure analysis revealed comparable intermetallic Cu...Cu distances (approximately 3.5 A) for the complexes 2 and 3. Despite this similarity, the composition of the complexes differs significantly in aqueous solution as revealed by spectrophotometric titrations. The hydrolysis of selected nitrophenylglycopyranosides is up to 11,000-fold accelerated over background in the presence of the copper(II) complexes in 3-(cyclohexylamino)-1-propanesulfonic acid (CAPS) buffer at pH 10.5 and 30 degrees C.


Subject(s)
Copper/chemistry , Glycosides/chemistry , Catalysis , Hydrogen-Ion Concentration , Hydrolysis , Magnetic Resonance Spectroscopy , Mass Spectrometry , Models, Molecular , Molecular Structure , Spectrophotometry, Infrared , X-Ray Diffraction
15.
Science ; 280(5363): 564-7, 1998 Apr 24.
Article in English | MEDLINE | ID: mdl-9554842

ABSTRACT

Tree-ring data from Virginia indicate that the Lost Colony of Roanoke Island disappeared during the most extreme drought in 800 years (1587-1589) and that the alarming mortality and the near abandonment of Jamestown Colony occurred during the driest 7-year episode in 770 years (1606-1612). These extraordinary droughts can now be implicated in the fate of the Lost Colony and in the appalling death rate during the early occupations at Jamestown, the first permanent English settlement in America.


Subject(s)
Disasters/history , Mortality , Climate , Fresh Water , History, 16th Century , History, 17th Century , Humans , Nutrition Disorders/history , Starvation/history , Virginia
17.
Inorg Chem ; 48(10): 4530-5, 2009 May 18.
Article in English | MEDLINE | ID: mdl-19348443

ABSTRACT

The hydrothermal reactions of both PuO(2)(2+) and PuO(2) with phosphonates results in the formation of Pu(IV) phosphonates. Pu(CH(3)PO(3))(2), Pu[CH(2)(PO(3))(2)](H(2)O), and UO(2)Pu(H(2)O)(2)[CH(2)(PO(3))(PO(3)H)](2) have been isolated from these reactions and structurally characterized. Pu(CH(3)PO(3))(2) contains six-coordinate Pu(IV) and adopts a structure closely related to that of alpha-Zr(HPO(4))(2). Pu[CH(2)(PO(3))(2)](H(2)O) forms a novel three-dimensional network with seven-coordinate Pu(IV) and chelating/bridging [CH(2)(PO(3))(2)](4-) anions. The heterobimetallic U(VI)/Pu(IV) diphosphonate, UO(2)Pu(H(2)O)(2)[CH(2)(PO(3))(PO(3)H)](2), also forms a three-dimensional network. To complete the An[CH(2)(PO(3))(2)](H(2)O)(n) (An = Th, U, Np, Pu; n = 1, 2) and UO(2)An(H(2)O)(2)[CH(2)(PO(3))(PO(3)H)](2) series, Th[CH(2)(PO(3))(2)](H(2)O)(2) and UO(2)Th(H(2)O)(2)[CH(2)(PO(3))(PO(3)H)](2) have also been prepared. These compounds are isostructural with their Np(IV) analogues.

18.
J Morphol ; 279(4): 458-471, 2018 04.
Article in English | MEDLINE | ID: mdl-29178494

ABSTRACT

Odontocetes have specialized mandibular fats, the extramandibular (EMFB) and intramandibular fat bodies (IMFB), which function as acoustic organs, receiving and channeling sound to the ear during hearing and echolocation. Recent strandings of beaked whales suggest that these fat bodies are susceptible to nitrogen (N2 ) gas embolism and empirical evidence has shown that the N2 solubility of these fat bodies is higher than that of blubber. Since N2 gas will diffuse from blood into tissue at any blood/tissue interface and potentially form gas bubbles upon decompression, it is imperative to understand the extent of microvascularity in these specialized acoustic fats so that risk of embolism formation when diving can be estimated. Microvascular density was determined in the EMFB, IMFB, and blubber from 11 species representing three odontocete families. In all cases, the acoustic tissues had less (typically 1/3 to 1/2) microvasculature than did blubber, suggesting that capillary density in the acoustic tissues may be more constrained than in the blubber. However, even within these constraints there were clear phylogenetic differences. Ziphiid (Mesoplodon and Ziphius, 0.9 ± 0.4% and 0.7 ± 0.3% for EMFB and IMFB, respectively) and Kogiid families (1.2 ± 0.2% and 1.0 ± 0.01% for EMFB and IMFB, respectively) had significantly lower mean microvascular densities in the acoustic fats compared to the Delphinid species (Tursiops, Grampus, Stenella, and Globicephala, 1.3 ± 0.3% and 1.3 ± 0.3% for EMFB and IMFB, respectively). Overall, deep-diving beaked whales had less microvascularity in both mandibular fats and blubber compared to the shallow-diving Delphinids, which might suggest that there are differences in the N2 dynamics associated with diving regime, phylogeny, and tissue type. These novel data should be incorporated into diving physiology models to further understand potential functional disruption of the acoustic tissues due to changes in normal diving behavior.


Subject(s)
Acoustics , Adipose Tissue/blood supply , Diving/physiology , Dolphins/anatomy & histology , Dolphins/physiology , Microvessels/anatomy & histology , Whales/classification , Whales/physiology , Adipose Tissue/anatomy & histology , Animals , Esters/analysis , Lipids/analysis , Phylogeny , Waxes/analysis
19.
Nat Commun ; 9(1): 1132, 2018 03 19.
Article in English | MEDLINE | ID: mdl-29556067

ABSTRACT

Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+ stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that crypts become rapidly derived from a single stem cell. Stem cells located further from the base are lost and the pool of competing stem cells is reduced. We tested whether this loss of stem cell competition would modify tumorigenesis. Reduction of Wnt ligand secretion accelerates fixation of Apc-deficient cells within the crypt leading to accelerated tumorigenesis. Therefore, ligand-based Wnt signalling influences the number of stem cells, fixation speed of Apc mutations and the speed and likelihood of adenoma formation.


Subject(s)
Carcinogenesis/metabolism , Cell Transformation, Neoplastic/metabolism , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Stem Cells/cytology , Stem Cells/metabolism , Wnt Signaling Pathway , Acyltransferases/antagonists & inhibitors , Adenoma/etiology , Adenoma/metabolism , Adenoma/pathology , Adenomatous Polyposis Coli Protein/deficiency , Adenomatous Polyposis Coli Protein/genetics , Adenomatous Polyposis Coli Protein/metabolism , Animals , Carcinogenesis/drug effects , Cell Transformation, Neoplastic/drug effects , Colorectal Neoplasms/etiology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Enzyme Inhibitors/pharmacology , Intestinal Mucosa/drug effects , Ligands , Membrane Proteins/antagonists & inhibitors , Mice , Mice, Inbred C57BL , Mice, Transgenic , Pyrazines/pharmacology , Pyridines/pharmacology , Stem Cells/drug effects , Wnt Signaling Pathway/drug effects
20.
Mol Cell Biol ; 8(3): 1224-35, 1988 Mar.
Article in English | MEDLINE | ID: mdl-2835666

ABSTRACT

The expression of tubulin polypeptides in animal cells is controlled by an autoregulatory mechanism whereby increases in the tubulin subunit concentration result in rapid and specific degradation of tubulin mRNAs. We have now determined that the sequences that are necessary and sufficient to specify mouse beta-tubulin mRNAs as substrates for this autoregulated instability reside within the first 13 translated nucleotides (which encode the first four beta-tubulin amino acids Met-Arg-Glu-Ile). This domain has been functionally conserved throughout evolution, inasmuch as sequences isolated from the analogous region of human, chicken, and yeast beta-tubulin mRNAs also confer autoregulation. Further, for an RNA to be a substrate for regulation, not only must it carry the 13-nucleotide coding sequence, but it must also be ribosome bound and its translation must proceed 3' to codon 41.


Subject(s)
Gene Expression Regulation , Polyribosomes/metabolism , RNA, Messenger/genetics , Tubulin/genetics , Amino Acid Sequence , Animals , Base Sequence , Biological Evolution , Chickens , Codon/genetics , Endonucleases , Genes , Humans , Mice , Molecular Sequence Data , Protein Biosynthesis , RNA, Messenger/metabolism , Single-Strand Specific DNA and RNA Endonucleases , Transfection
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