On Factors Affecting the Fixation of Chromosomal Rearrangements and Neutral Genes: Computer Simulations

Evolution ◽  
1986 ◽  
Vol 40 (3) ◽  
pp. 625 ◽  
Author(s):  
Ronald K. Chesser ◽  
Robert J. Baker
Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1932
Author(s):  
Barbora Pekova ◽  
Vlasta Sykorova ◽  
Karolina Mastnikova ◽  
Eliska Vaclavikova ◽  
Jitka Moravcova ◽  
...  

Chromosomal rearrangements of NTRK genes are oncogenic driver mutations in thyroid cancer (TC). This study aimed to identify NTRK fusion-positive thyroid tumors and to correlate them with clinical and pathological data and determine their prognostic significance. The cohort consisted of 989 different TC samples. Based on the detected mutation, samples were triaged, and those that were positive for a BRAF, HRAS, KRAS, NRAS, RET, RET/PTC or PAX8/PPARγ mutation were excluded from further analyses. NTRK fusion gene testing was performed in 259 cases, including 126 cases using next-generation sequencing. NTRK fusion genes were detected in 57 of 846 (6.7%) papillary thyroid carcinomas and in 2 of 10 (20.0%) poorly differentiated thyroid carcinomas. A total of eight types of NTRK fusions were found, including ETV6/NTRK3, EML4/NTRK3, RBPMS/NTRK3, SQSTM1/NTRK3, TPM3/NTRK1, IRF2BP2/NTRK1, SQSTM1/NTRK1 and TPR/NTRK1.NTRK fusion-positive carcinomas were associated with the follicular growth pattern, chronic lymphocytic thyroiditis and lymph node metastases. NTRK1-rearranged carcinomas showed a higher frequency of multifocality and aggressivity than NTRK3-rearranged carcinomas. Tumor size, presence of metastases, positivity for the NTRK3 or NTRK1 fusion gene and a late mutation event (TERT or TP53 mutation) were determined as factors affecting patient prognosis. NTRK fusion genes are valuable diagnostic and prognostic markers.


1968 ◽  
Vol 10 (1) ◽  
pp. 91-98 ◽  
Author(s):  
M. Joneja ◽  
S. Ungthavorn

Pregnant Swiss mice were injected with trypan blue on the 9th day of gestation. Analyses of anaphase-telophases revealed a high incidence of mitotic irregularities such as chromosome bridges, fragments or both, in the embryos. As a result of chromosomal rearrangements followed by mitotic aberrations, karyotypically abnormal cells were formed in the embryos and they had a relatively higher incidence of such abnormal cells than the untreated controls. This study does not suggest any direct causal relationship between chromosomal lesions induced and the teratogenic effects of trypan blue. However, it is possible that these aberrations are factors affecting the viability and proliferative capacities of the embryonic cells.


2021 ◽  
Author(s):  
Michael Kreindel ◽  
Stephen Mulholland

This chapter outlines the basic science and specific principles of operation for radiofrequency (RF) technologies with a focus on minimally-invasive applications enhancing liposuction procedure. Before discussing the parameters, settings and techniques for radiofrequency-assisted lipolysis (RFAL) and fractional RF subdermal treatment, it is important to understand the fundamentals of the basic science of RF technologies and applications. The chapter accurately describes the physics of the processes occurring during RF-based treatment, and the factors affecting its safe and efficacious outcome. The discussion of RF-based devices will use terminology and definitions provided by FDA guidance for electrosurgical devices. Measurements and computer simulations conducted by the authors to illustrate importance of different parameters for the specific treatments of skin and subcutaneous fat are also presented.


2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Tovah A. Day ◽  
Jacob V. Layer ◽  
J. Patrick Cleary ◽  
Srijoy Guha ◽  
Kristen E. Stevenson ◽  
...  

Abstract Chromosomal rearrangements are essential events in the pathogenesis of both malignant and nonmalignant disorders, yet the factors affecting their formation are incompletely understood. Here we develop a zinc-finger nuclease translocation reporter and screen for factors that modulate rearrangements in human cells. We identify UBC9 and RAD50 as suppressors and 53BP1, DDB1 and poly(ADP)ribose polymerase 3 (PARP3) as promoters of chromosomal rearrangements across human cell types. We focus on PARP3 as it is dispensable for murine viability and has druggable catalytic activity. We find that PARP3 regulates G quadruplex (G4) DNA in response to DNA damage, which suppresses repair by nonhomologous end-joining and homologous recombination. Chemical stabilization of G4 DNA in PARP3 −/− cells leads to widespread DNA double-strand breaks and synthetic lethality. We propose a model in which PARP3 suppresses G4 DNA and facilitates DNA repair by multiple pathways.


Author(s):  
F. A. Heckman ◽  
E. Redman ◽  
J.E. Connolly

In our initial publication on this subject1) we reported results demonstrating that contrast is the most important factor in producing the high image quality required for reliable image analysis. We also listed the factors which enhance contrast in order of the experimentally determined magnitude of their effect. The two most powerful factors affecting image contrast attainable with sheet film are beam intensity and KV. At that time we had only qualitative evidence for the ranking of enhancing factors. Later we carried out the densitometric measurements which led to the results outlined below.Meaningful evaluations of the cause-effect relationships among the considerable number of variables in preparing EM negatives depend on doing things in a systematic way, varying only one parameter at a time. Unless otherwise noted, we adhered to the following procedure evolved during our comprehensive study:Philips EM-300; 30μ objective aperature; magnification 7000- 12000X, exposure time 1 second, anti-contamination device operating.


Author(s):  
R. Gronsky

The phenomenon of clustering in Al-Ag alloys has been extensively studied since the early work of Guinierl, wherein the pre-precipitation state was characterized as an assembly of spherical, ordered, silver-rich G.P. zones. Subsequent x-ray and TEM investigations yielded results in general agreement with this model. However, serious discrepancies were later revealed by the detailed x-ray diffraction - based computer simulations of Gragg and Cohen, i.e., the silver-rich clusters were instead octahedral in shape and fully disordered, atleast below 170°C. The object of the present investigation is to examine directly the structural characteristics of G.P. zones in Al-Ag by high resolution transmission electron microscopy.


Author(s):  
E. H. Egelman ◽  
X. Yu

The RecA protein of E. coli has been shown to mediate genetic recombination, regulate its own synthesis, control the expression of other genes, act as a specific protease, form a helical polymer and have an ATPase activity, among other observed properties. The unusual filament formed by the RecA protein on DNA has not previously been shown to exist outside of bacteria. Within this filament, the 36 Å pitch of B-form DNA is extended to about 95 Å, the pitch of the RecA helix. We have now establishedthat similar nucleo-protein complexes are formed by bacteriophage and yeast proteins, and availableevidence suggests that this structure is universal across all of biology, including humans. Thus, understanding the function of the RecA protein will reveal basic mechanisms, in existence inall organisms, that are at the foundation of general genetic recombination and repair.Recombination at this moment is assuming an importance far greater than just pure biology. The association between chromosomal rearrangements and neoplasms has become stronger and stronger, and these rearrangements are most likely products of the recombinatory apparatus of the normal cell. Further, damage to DNA appears to be a major cause of cancer.


Author(s):  
R. Herrera ◽  
A. Gómez

Computer simulations of electron diffraction patterns and images are an essential step in the process of structure and/or defect elucidation. So far most programs are designed to deal specifically with crystals, requiring frequently the space group as imput parameter. In such programs the deviations from perfect periodicity are dealt with by means of “periodic continuation”.However, for many applications involving amorphous materials, quasiperiodic materials or simply crystals with defects (including finite shape effects) it is convenient to have an algorithm capable of handling non-periodicity. Our program “HeGo” is an implementation of the well known multislice equations in which no periodicity assumption is made whatsoever. The salient features of our implementation are: 1) We made Gaussian fits to the atomic scattering factors for electrons covering the whole periodic table and the ranges [0-2]Å−1 and [2-6]Å−1.


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