scholarly journals Key roles of CCCTC-binding factor in cancer evolution and development

2021 ◽  
pp. Online First
Author(s):  
Zishuai Li ◽  
Xinyu Zhou ◽  
Shiliang Cai ◽  
Junyan Fan ◽  
Zhimin Wei ◽  
...  
Keyword(s):  
Tumor Development ◽  
Three Dimensional ◽  
Suppressor Gene ◽  
Cancer Evolution ◽  
Evolution And Development ◽  
Binding Factor ◽  
Human Embryogenesis ◽  
History Of ◽  
3D Chromatin Structure ◽  
Regulatory Functions

The processes of cancer and embryonic development have a partially overlapping effect. Several transcription factor families, which are highly conserved in the evolutionary history of biology, play a key role in the development of cancer and are often responsible for the pivotal developmental processes such as cell survival, expansion, senescence, and differentiation. As an evolutionary conserved and ubiquitously expression protein, CCCTC-binding factor (CTCF) has diverse regulatory functions, including gene regulation, imprinting, insulation, X chromosome inactivation, and the establishment of three-dimensional (3D) chromatin structure during human embryogenesis. In various cancers, CTCF is considered as a tumor suppressor gene and plays homeostatic roles in maintaining genome function and integrity. However, the mechanisms of CTCF in tumor development have not been fully elucidated. Here, this review will focus on the key roles of CTCF in cancer evolution and development (Cancer Evo-Dev) and embryogenesis.

scholarly journals The role of CTCF in regulating nuclear organization

2008 ◽  
Vol 205 (4) ◽  
pp. 747-750 ◽  
Author(s):  
Adam Williams ◽  
Richard A. Flavell
Keyword(s):  
Long Range ◽  
Dna Sequences ◽  
Spatial Organization ◽  
Zinc Finger Protein ◽  
Nuclear Organization ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Binding Factor ◽  
Long Range Interactions ◽  
Regulatory Functions

The spatial organization of the genome is thought to play an important part in the coordination of gene regulation. New techniques have been used to identify specific long-range interactions between distal DNA sequences, revealing an ever-increasing complexity to nuclear organization. CCCTC-binding factor (CTCF) is a versatile zinc finger protein with diverse regulatory functions. New data now help define how CTCF mediates both long-range intrachromosomal and interchromosomal interactions, and highlight CTCF as an important factor in determining the three-dimensional structure of the genome.

scholarly journals The future: genetics advances in MEN1 therapeutic approaches and management strategies

2017 ◽  
Vol 24 (10) ◽  
pp. T119-T134 ◽  
Author(s):  
Sunita K Agarwal
Keyword(s):  
Genetic Testing ◽  
Tumor Suppressor ◽  
Mouse Models ◽  
Target Genes ◽  
Molecular Genetic ◽  
Management Strategies ◽  
Tumor Development ◽  
Three Dimensional ◽  
Suppressor Gene ◽  
Dimensional Structure

The identification of the multiple endocrine neoplasia type 1 (MEN1) gene in 1997 has shown that germline heterozygous mutations in theMEN1gene located on chromosome 11q13 predisposes to the development of tumors in the MEN1 syndrome. Tumor development occurs upon loss of the remaining normal copy of theMEN1gene in MEN1-target tissues. Therefore,MEN1is a classic tumor suppressor gene in the context of MEN1. This tumor suppressor role of the protein encoded by theMEN1gene, menin, holds true in mouse models with germline heterozygousMen1loss, wherein MEN1-associated tumors develop in adult mice after spontaneous loss of the remaining non-targeted copy of theMen1gene. The availability of genetic testing for mutations in theMEN1gene has become an essential part of the diagnosis and management of MEN1. Genetic testing is also helping to exclude mutation-negative cases in MEN1 families from the burden of lifelong clinical screening. In the past 20 years, efforts of various groups world-wide have been directed at mutation analysis, molecular genetic studies, mouse models, gene expression studies, epigenetic regulation analysis, biochemical studies and anti-tumor effects of candidate therapies in mouse models. This review will focus on the findings and advances from these studies to identifyMEN1germline and somatic mutations, the genetics of MEN1-related states, several protein partners of menin, the three-dimensional structure of menin and menin-dependent target genes. The ongoing impact of all these studies on disease prediction, management and outcomes will continue in the years to come.

scholarly journals pVHL Modification by NEDD8 Is Required for Fibronectin Matrix Assembly and Suppression of Tumor Development

2004 ◽  
Vol 24 (8) ◽  
pp. 3251-3261 ◽  
Author(s):  
Natalie H. Stickle ◽  
Jacky Chung ◽  
Jeffery M. Klco ◽  
Richard P. Hill ◽  
William G. Kaelin ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Tumor Development ◽  
Three Dimensional ◽  
Suppressor Gene ◽  
Matrix Assembly ◽  
Von Hippel Lindau ◽  
Fibronectin Matrix ◽  
Matrix Expression ◽  
Vhl Disease ◽  
Hif Pathway

ABSTRACT Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is the cause of the familial VHL disease and most sporadic renal clear-cell carcinomas (RCC). pVHL has been shown to play a role in the destruction of hypoxia-inducible factor α (HIF-α) subunits via ubiquitin-mediated proteolysis and in the regulation of fibronectin matrix assembly. Although most disease-causing pVHL mutations hinder the regulation of the HIF pathway, every disease-causing pVHL mutant tested to date has failed to promote the assembly of the fibronectin matrix, underscoring its potential importance in VHL disease. Here, we report that a ubiquitin-like molecule called NEDD8 covalently modifies pVHL. A nonneddylateable pVHL mutant, while retaining its ability to ubiquitylate HIF, failed to bind to and promote the assembly of the fibronectin matrix. Expression of the neddylation-defective pVHL in RCC cells, while restoring the regulation of HIF, failed to promote the differentiated morphology in a three-dimensional growth assay and was insufficient to suppress the formation of tumors in SCID mice. These results suggest that NEDD8 modification of pVHL plays an important role in fibronectin matrix assembly and that in the absence of such regulation, an intact HIF pathway is insufficient to prevent VHL-associated tumorigenesis.

Sea Urchins and Circuses: The Modernist Natural Histories of Jean Painlevé and Alexander Calder

2018 ◽  
Vol 13 (2) ◽  
pp. 187-211
Author(s):  
Patricia E. Chu
Keyword(s):  
New Media ◽  
Sea Urchins ◽  
Life Sciences ◽  
Three Dimensional ◽  
Machine Age ◽  
Avant Garde ◽  
History Of ◽  
And Performance ◽  
The One ◽  
Natural Historian

The Paris avant-garde milieu from which both Cirque Calder/Calder's Circus and Painlevé’s early films emerged was a cultural intersection of art and the twentieth-century life sciences. In turning to the style of current scientific journals, the Paris surrealists can be understood as engaging the (life) sciences not simply as a provider of normative categories of materiality to be dismissed, but as a companion in apprehending the “reality” of a world beneath the surface just as real as the one visible to the naked eye. I will focus in this essay on two modernist practices in new media in the context of the history of the life sciences: Jean Painlevé’s (1902–1989) science films and Alexander Calder's (1898–1976) work in three-dimensional moving art and performance—the Circus. In analyzing Painlevé’s work, I discuss it as exemplary of a moment when life sciences and avant-garde technical methods and philosophies created each other rather than being classified as separate categories of epistemological work. In moving from Painlevé’s films to Alexander Calder's Circus, Painlevé’s cinematography remains at the forefront; I use his film of one of Calder's performances of the Circus, a collaboration the men had taken two decades to complete. Painlevé’s depiction allows us to see the elements of Calder's work that mark it as akin to Painlevé’s own interest in a modern experimental organicism as central to the so-called machine-age. Calder's work can be understood as similarly developing an avant-garde practice along the line between the bestiary of the natural historian and the bestiary of the modern life scientist.

Computed Tomography and Magnetic Resonance Imaging-aided Diagnosis of Primary Essential Cutis Verticis Gyrata: A Case Report with 5-year Follow-up and Review of the Literature

2019 ◽  
Vol 15 (9) ◽  
pp. 906-910
Author(s):  
Hongzhang Zhu ◽  
Shi-Ting Feng ◽  
Xingqi Zhang ◽  
Zunfu Ke ◽  
Ruixi Zeng ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Three Dimensional ◽  
Stable Condition ◽  
Resonance Imaging ◽  
Mri Findings ◽  
Cutis Verticis Gyrata ◽  
Essential Form ◽  
History Of ◽  
Magnetic Resonance Imaging Mri

Background: Cutis Verticis Gyrata (CVG) is a rare skin disease caused by overgrowth of the scalp, presenting as cerebriform folds and wrinkles. CVG can be classified into two forms: primary (essential and non-essential) and secondary. The primary non-essential form is often associated with neurological and ophthalmological abnormalities, while the primary essential form occurs without associated comorbidities. Discussion: We report on a rare case of primary essential CVG with a 4-year history of normal-colored scalp skin mass in the parietal-occipital region without symptom in a 34-year-old male patient, retrospectively summarizing his pathological and Computer Tomography (CT) and magnetic resonance imaging (MRI) findings. The major clinical observations on the CT and MR sectional images include a thickened dermis and excessive growth of the scalp, forming the characteristic scalp folds. With the help of CT and MRI Three-dimensional (3D) reconstruction techniques, the characteristic skin changes could be displayed intuitively, providing more evidence for a diagnosis of CVG. At the 5-year followup, there were no obvious changes in the lesion. Conclusion: Based on our observations, we propose that not all patients with primary essential CVG need surgical intervention, and continuous clinical observation should be an appropriate therapy for those in stable condition.

scholarly journals Sirenomelia: two case reports

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Asiyeh Shojaee ◽  
Firooze Ronnasian ◽  
Mahdiyeh Behnam ◽  
Mansoor Salehi
Keyword(s):  
Case Reports ◽  
Three Dimensional ◽  
First Trimester ◽  
Mendelian Inheritance ◽  
Lower Limbs ◽  
Congenital Deformity ◽  
White Family ◽  
Her Family ◽  
Caudal Regression ◽  
History Of

AbstractBackgroundSirenomelia, also called mermaid syndrome, is a rare lethal multi-system congenital deformity with an incidence of one in 60,000–70,000 pregnancies. Sirenomelia is mainly characterized by the fusion of lower limbs and is widely associated with severe urogenital and gastrointestinal malformations. The presence of a single umbilical artery derived from the vitelline artery is the main anatomical feature distinguishing sirenomelia from caudal regression syndrome. First-trimester diagnosis of this disorder and induced abortion may be the safest medical option. In this report, two cases of sirenomelia that occurred in an white family will be discussed.Case presentationWe report two white cases of sirenomelia occurring in a 31-year-old multigravid pregnant woman. In the first pregnancy (18 weeks of gestation) abortion was performed, but in the third pregnancy (32 weeks) the stillborn baby was delivered by spontaneous vaginal birth. In the second and fourth pregnancies, however, she gave birth to normal babies. Three-dimensional ultrasound imaging showed fusion of the lower limbs. Neither she nor any member of her family had a history of diabetes. In terms of other risk factors, she had no history of exposure to teratogenic agents during her pregnancy. Also, her marriage was non-consanguineous.ConclusionThis report suggests the existence of a genetic background in this mother with a Mendelian inheritance pattern of 50% second-generation incidence in her offspring.

scholarly journals Galaxy and mass assembly (GAMA): the inferred mass–metallicity relation from z = 0 to 3.5 via forensic SED fitting

2021 ◽  
Vol 503 (3) ◽  
pp. 3309-3325
Author(s):  
Sabine Bellstedt ◽  
Aaron S G Robotham ◽  
Simon P Driver ◽  
Jessica E Thorne ◽  
Luke J M Davies ◽  
...  
Keyword(s):  
Star Formation ◽  
Gas Phase ◽  
Large Range ◽  
Three Dimensional ◽  
Cosmic Time ◽  
Slowing Down ◽  
History Of ◽  
Mass Assembly ◽  
Star Formation Histories ◽  
Cosmic History

ABSTRACT We analyse the metallicity histories of ∼4500 galaxies from the GAMA survey at z < 0.06 modelled by the SED-fitting code ProSpect using an evolving metallicity implementation. These metallicity histories, in combination with the associated star formation histories, allow us to analyse the inferred gas-phase mass–metallicity relation. Furthermore, we extract the mass–metallicity relation at a sequence of epochs in cosmic history, to track the evolving mass–metallicity relation with time. Through comparison with observations of gas-phase metallicity over a large range of redshifts, we show that, remarkably, our forensic SED analysis has produced an evolving mass–metallicity relationship that is consistent with observations at all epochs. We additionally analyse the three-dimensional mass–metallicity–SFR space, showing that galaxies occupy a clearly defined plane. This plane is shown to be subtly evolving, displaying an increased tilt with time caused by general enrichment, and also the slowing down of star formation with cosmic time. This evolution is most apparent at lookback times greater than 7 Gyr. The trends in metallicity recovered in this work highlight that the evolving metallicity implementation used within the SED-fitting code ProSpect produces reasonable metallicity results over the history of a galaxy. This is expected to provide a significant improvement to the accuracy of the SED-fitting outputs.

scholarly journals A Variance Gamma model for Rugby Union matches

2020 ◽  
Vol 17 (1) ◽  
pp. 67-75
Author(s):  
John Fry ◽  
Oliver Smart ◽  
Jean-Philippe Serbera ◽  
Bernhard Klar
Keyword(s):  
Three Dimensional ◽  
Rugby Union ◽  
Three Dimensional Model ◽  
Gamma Model ◽  
Variance Gamma ◽  
Poisson Models ◽  
History Of ◽  
Bonus Points ◽  
Variance Gamma Model ◽  
Special Case

Abstract Amid much recent interest we discuss a Variance Gamma model for Rugby Union matches (applications to other sports are possible). Our model emerges as a special case of the recently introduced Gamma Difference distribution though there is a rich history of applied work using the Variance Gamma distribution – particularly in finance. Restricting to this special case adds analytical tractability and computational ease. Our three-dimensional model extends classical two-dimensional Poisson models for soccer. Analytical results are obtained for match outcomes, total score and the awarding of bonus points. Model calibration is demonstrated using historical results, bookmakers’ data and tournament simulations.

A Three-Dimensional Finite Difference Solution for the Thermal Stresses in Railcar Wheels

1969 ◽  
Vol 91 (3) ◽  
pp. 891-896 ◽  
Author(s):  
G. E. Novak ◽  
B. J. Eck
Keyword(s):  
Computer Program ◽  
Thermal Stresses ◽  
Three Dimensional ◽  
Transient Temperature ◽  
Shear Stresses ◽  
Radial Temperature ◽  
Closed Form Solutions ◽  
Brake Application ◽  
History Of ◽  
Thin Disks

A numerical solution is presented for both the transient temperature and three-dimensional stress distribution in a railcar wheel resulting from a simulated emergency brake application. A computer program has been written for generating thermoelastic solutions applicable to wheels of arbitrary contour with temperature variations in both axial and radial directions. The results include the effect of shear stresses caused by the axial-radial temperature gradients and the high degree of boundary irregularity associated with this type of problem. The program has been validated by computing thermoelastic solutions for thin disks and long cylinders; the computed values being in good agreement with the closed form solutions. Currently, the computer program is being extended to general stress solutions corresponding to the transient temperature distributions obtained by simulated drag brake applications. When this work is completed, it will be possible to synthesize the thermal history of a railcar wheel and investigate the effects of wheel geometry in relation to thermal fatigue.

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