Chromosome Missegregation as a Modulator of Radiation Sensitivity

2022 ◽  
Vol 32 (1) ◽  
pp. 54-63
Author(s):  
Pippa F. Cosper ◽  
Sarah E. Copeland ◽  
John B. Tucker ◽  
Beth A. Weaver
Keyword(s):  
Radiation Sensitivity ◽  
Chromosome Missegregation

Design of Sensitive Photographic Materials for the High-Voltage Electron Microscope

1975 ◽  
Vol 33 ◽  
pp. 156-157
Author(s):  
Murray Vernon King ◽  
Donald F. Parsons
Keyword(s):  
Electron Microscope ◽  
Radiation Damage ◽  
High Voltage ◽  
Radiation Sensitivity ◽  
Fast Electrons ◽  
Voltage Electron ◽  
High Voltage Electron Microscope ◽  
High Voltage Electron ◽  
Biological Studies ◽  
Low Sensitivity

Effective application of the high-voltage electron microscope to a wide variety of biological studies has been restricted by the radiation sensitivity of biological systems. The problem of radiation damage has been recognized as a serious factor influencing the amount of information attainable from biological specimens in electron microscopy at conventional voltages around 100 kV. The problem proves to be even more severe at higher voltages around 1 MV. In this range, the problem is the relatively low sensitivity of the existing recording media, which entails inordinately long exposures that give rise to severe radiation damage. This low sensitivity arises from the small linear energy transfer for fast electrons. Few developable grains are created in the emulsion per electron, while most of the energy of the electrons is wasted in the film base.

Anisotropic radiation damage of potassium tetracyano platinate (KCP)

1978 ◽  
Vol 36 (1) ◽  
pp. 392-393
Author(s):  
N. Uyeda ◽  
E. J. Kirkland ◽  
B. M. Siegel
Keyword(s):  
Electron Diffraction ◽  
Radiation Damage ◽  
Structural Changes ◽  
High Resolution Electron Microscopy ◽  
Radiation Sensitivity ◽  
Resolution Electron ◽  
Damage Process ◽  
Diffraction Patterns ◽  
Fading Rate

The direct observation of structural change by high resolution electron microscopy will be essential for the better understanding of the damage process and its mechanism. However, this approach still involves some difficulty in quantitative interpretation mostly being due to the quality of obtained images. Electron diffraction, using crystalline specimens, has been the method most frequently applied to obtain a comparison of radiation sensitivity of various materials on the quantitative base. If a series of single crystal patterns are obtained the fading rate of reflections during the damage process give good comparative measures. The electron diffraction patterns also render useful information concerning the structural changes in the crystal. In the present work, the radiation damage of potassium tetracyano-platinate was dealt with on the basis two dimensional observation of fading rates of diffraction spots. KCP is known as an ionic crystal which possesses “one dimensional” electronic properties and it would be of great interest to know if radiation damage proceeds in a strongly asymmetric manner.

High-resolution topographic SEM and radiation damage: The rationale for using low beam voltage

1992 ◽  
Vol 50 (2) ◽  
pp. 1278-1279
Author(s):  
James Pawley ◽  
David Joy
Keyword(s):  
High Resolution ◽  
Imaging Techniques ◽  
Morphological Structure ◽  
Radiation Sensitivity ◽  
Beam Specimen ◽  
Measured Signal ◽  
Practical Consideration ◽  
Interaction Volume ◽  
Impact Area ◽  
Signal Contrast

The scanning electron microscope (SEM) builds up an image by sampling contiguous sub-volumes near the surface of the specimen. A fine electron beam selectively excites each sub-volume and then the intensity of some resulting signal is measured and then plotted as a corresponding intensity in an image. The spatial resolution of such an image is limited by at least three factors. Two of these determine the size of the interaction volume: the size of the electron probe and the extent to which detectable signal is excited from locations remote from the beam impact area. A third limitation emerges from the fact that the probing beam is composed of a number of discrete particles and therefore that the accuracy with which any detectable signal can be measured is limited by Poisson statistics applied to this number (or to the number of events actually detected if this is smaller). As in all imaging techniques, the limiting signal contrast required to recognize a morphological structure is constrained by this statistical consideration. The only way to overcome this limit is to increase either the contrast of the measured signal or the number of beam/specimen interactions detected. Unfortunately, these interactions deposit ionizing radiation that may damage the very structure under investigation. As a result, any practical consideration of the high resolution performance of the SEM must consider not only the size of the interaction volume but also the contrast available from the signal producing the image and the radiation sensitivity of the specimen.

Projected Structure of the Surface Protein of Sulfolobus Spec. B12 Determined to a Resolution of 1.0 NM by Cryo-Electronmicroscopy

1990 ◽  
Vol 48 (1) ◽  
pp. 102-103
Author(s):  
G. Lembcke ◽  
F. Zemlin
Keyword(s):  
Low Dose ◽  
Maximum Dose ◽  
Three Dimensional ◽  
Surface Protein ◽  
Protein S ◽  
Radiation Sensitivity ◽  
Specimen Preparation ◽  
Molecular Architecture ◽  
High Radiation ◽  
Fritz Haber

The thermoacidophilic archaebacterium Sulfolobus spec. B12 , which is closely related to Sulfolobus solfataricus , possesses a regularly arrayed surface protein (S-layer), which is linked to the plasma membrane via spacer elements spanning a distinct interspace of approximately 18 nm. The S-layer has p3-Symmetry and a lattice constant of 21 nm; three-dimensional reconstructions of negatively stained fragments yield a layer thickness of approximately 6-7 nm.For analysing the molecular architecture of Sulfolobus surface protein in greater detail we use aurothioglucose(ATG)-embedding for specimen preparation. Like glucose, ATG, is supposed to mimic the effect of water, but has the advantage of being less volatile. ATG has advantages over glucose when working with specimens composed exclusively of protein because of its higher density of 2.92 g cm-3. Because of its high radiation sensitivity electromicrographs has to be recorded under strict low-dose conditions. We have recorded electromicrographs with a liquid helium-cooled superconducting electron microscope (the socalled SULEIKA at the Fritz-Haber-lnstitut) with a specimen temperature of 4.5 K and with a maximum dose of 2000 e nm-2 avoiding any pre-irradiation of the specimen.

Pulsed Laser Stimulation Coupled with Optical Failure Analysis Technique—A Methodology to Help Space Application Electrical Designers

2015 ◽  
Author(s):  
G. Bascoul ◽  
K. Sanchez ◽  
G. Perez ◽  
F. Bezerra ◽  
H. Chauvin
Keyword(s):  
Heavy Ions ◽  
Pulsed Laser ◽  
Radiation Sensitivity ◽  
Radiation Environment ◽  
Physical Analysis ◽  
Space Application ◽  
Voltage Converter ◽  
Industrial Laboratory ◽  
Sensitivity Evaluation ◽  
Analysis Technique

Abstract Pulsed laser for radiation sensitivity evaluation has become a common tool used in research and industrial laboratory. This paper aims to highlight an approach to understand weaknesses of a component under radiation environment using a short pulsed width laser beam coupled to thermography technique, heavy ions test inputs and physical analysis. This paper is based on a study of a PWM device embedded on voltage converter.

scholarly journals CBIO-16. SUPPRESSION OF HISTONE H3.3 MITOTIC PHOSPHORYLATION DRIVES DEVELOPMENT OF H3K27M-MUTANT DIFFUSE MIDLINE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii18-ii19
Author(s):  
Charles Day ◽  
Alyssa Langfald ◽  
Florina Grigore ◽  
Leslie Sepaniac ◽  
Jason Stumpff ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Treatment Options ◽  
Chromosome Instability ◽  
Pericentromeric Heterochromatin ◽  
Low Grade ◽  
High Grade ◽  
Chromosome Missegregation ◽  
Mitotic Phosphorylation ◽  
Chk1 Kinase

Abstract Pediatric midline gliomas – including DIPG – are lethal brain tumors in children, with poor prognosis and limited treatment options that provide only short-term benefits. The majority have a lysine-to-methionine substitution at residue 27 (H3K27M) in genes expressing histone H3 – predominantly in the H3.3 variant. This causes a global reduction in H3 Lys27 tri-methylation (H3K27Me3), comprehensive epigenetic reprogramming, and is a key driver in gliomagenesis. We show that the H3.3K27M mutation also induces chromosome segregation defects, which in high-grade tumors, results in extensive copy number alterations (CNAs). Ser31 is one of five amino acid substitutions differentiating H3.3 from canonical H3.1. Mitotic phosphorylation of H3.3 Ser31 by Chk1 kinase is restricted to pericentromeric heterochromatin, where it plays a role in chromosome segregation. We show that the K27M mutation affects neighboring Ser31 phosphorylation and pericentromeric heterochromatin organization. We demonstrate that (i) H3.3 K27M protein is defective for Ser31 phosphorylation by Chk1 kinase in vitro; (ii) DIPG cell lines have significantly decreased mitotic Ser31 phosphorylation, and are chromosomally unstable; and (iii) CRISPR-reversion of H3.3K27M to Lys27 restores phospho-Ser31 (and Lys27 tri-methylation) and significantly decreases chromosome instability. Expression of H3.3K27M or non-phosphorylatable H3.3S31A mutants in WT cells results in chromosome missegregation; this is suppressed by co-expression of phospho-mimetic H3.3K27M/S31E. In normal cells, chromosome missegregation stimulates p53-dependent cell cycle arrest in G1 to prevent the proliferation of aneuploid daughters. However, cells expressing H3.3 K27M or S31A failed to arrest following missegregation - despite having WT p53. Finally, in a novel mouse model of glioma, mean survival of mice with tumors induced with H3.3K27M and H3.3S31A was 81 and 68 days: 100% of H3.3S31A mice developed high-grade tumors. H3.3 WT controls developed only low-grade tumors and all survived 100 days. H3.3S31A is WT for Lys27 tri-methylation and thus, loss of Ser31 phosphorylation alone is oncogenic.

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