scholarly journals DNA Polymerases at the Eukaryotic Replication Fork Thirty Years after: Connection to Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3489
Author(s):  
Youri I. Pavlov ◽  
Anna S. Zhuk ◽  
Elena I. Stepchenkova

Recent studies on tumor genomes revealed that mutations in genes of replicative DNA polymerases cause a predisposition for cancer by increasing genome instability. The past 10 years have uncovered exciting details about the structure and function of replicative DNA polymerases and the replication fork organization. The principal idea of participation of different polymerases in specific transactions at the fork proposed by Morrison and coauthors 30 years ago and later named “division of labor,” remains standing, with an amendment of the broader role of polymerase δ in the replication of both the lagging and leading DNA strands. However, cancer-associated mutations predominantly affect the catalytic subunit of polymerase ε that participates in leading strand DNA synthesis. We analyze how new findings in the DNA replication field help elucidate the polymerase variants’ effects on cancer.

Author(s):  
Edward G. Fey

In the past few years, considerable advances have been made regarding the structure and function of the nuclear matrix. In the first half of this presentation, the field of nuclear matrix research will be summarized. Emphasis will be placed on those studies where molecular interactions are demonstrated in situ utilizing high resolution light and/or electron microscopy. Studies demonstrating the role of the nuclear matrix in DNA synthesis and replication, RNA transcription and processing, and the binding of matrix attachment regions to specific nuclear matrix proteins will be summarized.


1982 ◽  
Vol 57 (3) ◽  
pp. 301-308 ◽  
Author(s):  
W. Kemp Clark

✓ The President of the American Association of Neurological Surgeons concentrates on the problems facing the specialty, the achievements of the past, and the mechanisms designed to foster the advancement and role of neurosurgery. To counter the difficult days ahead, he emphasizes the need for concerted effort and action on the part of neurosurgeons within the umbrella of the Association as spokesman for the specialty and advocate for the patients' welfare.


2001 ◽  
Vol 114 (15) ◽  
pp. 2723-2733 ◽  
Author(s):  
Paul G. McKean ◽  
Sue Vaughan ◽  
Keith Gull

Although most eukaryotic cells can express multiple isotypes of αβ-tubulin, the significance of this diversity has not always been apparent. Recent data indicate that particular αβ-tubulin isotypes, both genome encoded and those derived by post-translational modification, can directly influence microtubule structure and function — thus validating ideas originally proposed in the multitubulin hypothesis over 25 years ago.It has also become increasingly evident over the past year that some (but intriguingly not all) eukaryotes encode several other tubulin proteins, and to date five further members of the tubulin superfamily, γ, δ, ϵ, 𝛇 and η, have been identified. Although the role of γ-tubulin in the nucleation of microtubule assembly is now well established, far less is known about the functions of δ-, ϵ-, 𝛇- and η-tubulin. Recent work has expanded our knowledge of the functions and localisation of these newer members of the tubulin superfamily, and the emerging data suggesting a restricted evolutionary distribution of these `new' tubulin proteins, conforms to established knowledge of microtubule cell biology. On the basis of current evidence, we predict that δ-, ϵ-, 𝛇- and η-tubulin all have functions associated with the centriole or basal body of eukaryotic cells and organisms.


Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.


2020 ◽  
Vol 118 (3) ◽  
pp. 258a
Author(s):  
Laszlo Csernoch ◽  
Mónika Gönczi ◽  
Zsolt Ráduly ◽  
László Szabó ◽  
Nóra Dobrosi ◽  
...  

2021 ◽  
Vol 9 (1) ◽  
pp. 148
Author(s):  
Marius Bredon ◽  
Elisabeth Depuydt ◽  
Lucas Brisson ◽  
Laurent Moulin ◽  
Ciriac Charles ◽  
...  

The crucial role of microbes in the evolution, development, health, and ecological interactions of multicellular organisms is now widely recognized in the holobiont concept. However, the structure and stability of microbiota are highly dependent on abiotic and biotic factors, especially in the gut, which can be colonized by transient bacteria depending on the host’s diet. We studied these impacts by manipulating the digestive microbiota of the detritivore Armadillidium vulgare and analyzing the consequences on its structure and function. Hosts were exposed to initial starvation and then were fed diets that varied the different components of lignocellulose. A total of 72 digestive microbiota were analyzed according to the type of the diet (standard or enriched in cellulose, lignin, or hemicellulose) and the period following dysbiosis. The results showed that microbiota from the hepatopancreas were very stable and resilient, while the most diverse and labile over time were found in the hindgut. Dysbiosis and selective diets may have affected the host fitness by altering the structure of the microbiota and its predicted functions. Overall, these modifications can therefore have effects not only on the holobiont, but also on the “eco-holobiont” conceptualization of macroorganisms.


2021 ◽  
Vol 2 (2) ◽  
pp. 311-338
Author(s):  
Giulia Della Rosa ◽  
Clarissa Ruggeri ◽  
Alessandra Aloisi

Exosomes (EXOs) are nano-sized informative shuttles acting as endogenous mediators of cell-to-cell communication. Their innate ability to target specific cells and deliver functional cargo is recently claimed as a promising theranostic strategy. The glycan profile, actively involved in the EXO biogenesis, release, sorting and function, is highly cell type-specific and frequently altered in pathological conditions. Therefore, the modulation of EXO glyco-composition has recently been considered an attractive tool in the design of novel therapeutics. In addition to the available approaches involving conventional glyco-engineering, soft technology is becoming more and more attractive for better exploiting EXO glycan tasks and optimizing EXO delivery platforms. This review, first, explores the main functions of EXO glycans and associates the potential implications of the reported new findings across the nanomedicine applications. The state-of-the-art of the last decade concerning the role of natural polysaccharides—as targeting molecules and in 3D soft structure manufacture matrices—is then analysed and highlighted, as an advancing EXO biofunction toolkit. The promising results, integrating the biopolymers area to the EXO-based bio-nanofabrication and bio-nanotechnology field, lay the foundation for further investigation and offer a new perspective in drug delivery and personalized medicine progress.


Author(s):  
Rachel L. Leon ◽  
Imran N. Mir ◽  
Christina L. Herrera ◽  
Kavita Sharma ◽  
Catherine Y. Spong ◽  
...  

Abstract Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta–heart–brain connection. Impact Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.


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