scholarly journals Decoding the Oncogenic Signals from the Long Non-Coding RNAs

Onco ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 176-206
Author(s):  
Revathy Nadhan ◽  
Danny N. Dhanasekaran
Keyword(s):  
High Throughput Sequencing ◽  
Critical Role ◽  
Therapy Resistance ◽  
Signaling Cascades ◽  
Clear Understanding ◽  
Sequencing Technologies ◽  
Cancer Cell Survival ◽  
Non Coding Rnas ◽  
Insight Into

Cancer is one of the leading causes of death worldwide. Multifactorial etiology of cancer and tumor heterogeneity are the two most acute challenges in existing diagnostic and therapeutic strategies for cancer. An effective precision cancer medicine strategy to overcome these challenges requires a clear understanding of the transcriptomic landscape of cancer cells. Recent innovative breakthroughs in high-throughput sequencing technologies have identified the oncogenic or tumor-suppressor role of several long non-coding RNAs (lncRNAs). LncRNAs have been characterized as regulating various signaling cascades which are involved in the pathobiology of cancer. They modulate cancer cell survival, proliferation, metabolism, invasive metastasis, stemness, and therapy-resistance through their interactions with specific sets of proteins, miRNAs and other non-coding RNAs, mRNAs, or DNAs in cells. By virtue of their ability to regulate multiple sets of genes and their cognate signaling pathways, lncRNAs are emerging as potential candidates for diagnostic, prognostic, and therapeutic targets. This review is focused on providing insight into the mechanisms by which different lncRNAs play a critical role in cancer growth, and their potential role in cancer diagnosis, prognosis, and therapy.

scholarly journals Splicing dysregulation as a driver of breast cancer

2018 ◽  
Vol 25 (9) ◽  
pp. R467-R478 ◽  
Author(s):  
Abigail Read ◽  
Rachael Natrajan
Keyword(s):  
Breast Cancer ◽  
High Throughput Sequencing ◽  
Predictive Biomarkers ◽  
Therapy Resistance ◽  
Complete Understanding ◽  
Molecular Abnormalities ◽  
Sequencing Technologies ◽  
Large Repertoire ◽  
Positive Breast Cancer

Breast cancer is known to be a heterogeneous disease driven by a large repertoire of molecular abnormalities, which contribute to its diverse clinical behaviour. Despite the success of targeted therapy approaches for breast cancer patient management, there is still a lack of the molecular understanding of aggressive forms of the disease and clinical management of these patients remains difficult. The advent of high-throughput sequencing technologies has paved the way for a more complete understanding of the molecular make-up of the breast cancer genome. As such, it is becoming apparent that disruption of canonical splicing within breast cancer governs its clinical progression. In this review, we discuss the role of dysregulation of spliceosomal component genes and associated factors in the progression of breast cancer, their role in therapy resistance and the use of quantitative isoform expression as potential prognostic and predictive biomarkers with a particular focus on oestrogen receptor-positive breast cancer.

Science and Theology for Everyone: How Climate Science is Shaping Christianity in the UK

2021 ◽  
Vol 62 (2) ◽  
pp. 147-157
Author(s):  
Caleb Gordon ◽  
Hannah Malcolm
Keyword(s):  
Critical Role ◽  
Climate Science ◽  
Significant Shift ◽  
Christian Life ◽  
Ethical Problems ◽  
Technical Leadership ◽  
Science And Theology ◽  
The Uk ◽  
Insight Into

This article analyses the growing participation of UK Christians in climate initiatives over the last five years. In many cases, climate science is cited as a necessary consideration for the fulfilment of already-existing Christian commitments. This represents a significant shift in the ways UK Christians understand the role of dialogue between theology and the sciences; previous science and theology dialogue has usually been treated as an area of expert concern, primarily offering insight into apologetics or specific ethical problems. By contrast, the dialogue between climate science and theology has seen the emergence of non-technical leadership amid the expectation that climate science plays a critical role in re-examining the meaning of Christian life, both for individuals and as communities.

scholarly journals Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs

2018 ◽  
Author(s):  
David M. Kern ◽  
SeCheol Oh ◽  
Richard K. Hite ◽  
Stephen G. Brohawn
Keyword(s):  
Lipid Bilayers ◽  
Critical Role ◽  
Anion Channel ◽  
Lipid Binding ◽  
Channel Structure ◽  
Anion Channels ◽  
Cryo Electron Microscopy ◽  
Lipid Nanodiscs ◽  
Insight Into

AbstractHypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here we present single-particle cryo-electron microscopy structures of LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel.

The Cognitive Component of Elite High Jumpers’ Preperformance Routines

2020 ◽  
Vol 34 (2) ◽  
pp. 99-110
Author(s):  
Thomas Gretton ◽  
Lindsey Blom ◽  
Dorice Hankemeier ◽  
Lawrence Judge
Keyword(s):  
Thematic Analysis ◽  
Critical Role ◽  
Valuable Insight ◽  
Psychological Skills ◽  
Cognitive Content ◽  
Successful Performance ◽  
Cognitive Component ◽  
Inductive Thematic Analysis ◽  
Insight Into

Preperformance routines are microlevel performance processes utilized by athletes to facilitate the attainment of an optimal state and enhance the chance for successful performance. Despite continued examination of these routines, only a small proportion of research has been directed toward the cognitive component of these routines. This study explored the cognitive component of elite high jumpers’ preperformance routines, and specifically the consistency of the cognitive content (i.e., psychological skills and strategies). Data were acquired over an 8-week high-jump season and subjected to inductive thematic analysis. Results revealed the consistent implementation of the cognitive content (e.g., visualization) but an inconsistent design of this content (i.e., the content of the visualization). Furthermore, results underline the critical role of high-jump coaches and an athlete’s need to be adaptable and competent in utilizing various types of preperformance routine. This study offers valuable insight into the complexities and inconsistencies of the cognitive component of high jumpers’ preperformance routines.

Cryo-EM structure of 90S small ribosomal subunit precursors in transition states

Science ◽  
2020 ◽  
Vol 369 (6510) ◽  
pp. 1477-1481 ◽  
Author(s):  
Yifei Du ◽  
Weidong An ◽  
Xing Zhu ◽  
Qi Sun ◽  
Jia Qi ◽  
...  
Keyword(s):  
Structural Changes ◽  
Critical Role ◽  
Ribosomal Subunit ◽  
Rna Degradation ◽  
Ribosomal Subunits ◽  
Cryo Electron Microscopy ◽  
Nuclear Exosome ◽  
Assembly Intermediate ◽  
Insight Into

The 90S preribosome is a large, early assembly intermediate of small ribosomal subunits that undergoes structural changes to give a pre-40S ribosome. Here, we gained insight into this transition by determining cryo–electron microscopy structures of Saccharomyces cerevisiae intermediates in the path from the 90S to the pre-40S. The full transition is blocked by deletion of RNA helicase Dhr1. A series of structural snapshots revealed that the excised 5′ external transcribed spacer (5′ ETS) is degraded within 90S, driving stepwise disassembly of assembly factors and ribosome maturation. The nuclear exosome, an RNA degradation machine, docks on the 90S through helicase Mtr4 and is primed to digest the 3′ end of the 5′ ETS. The structures resolved between 3.2- and 8.6-angstrom resolution reveal key intermediates and the critical role of 5′ ETS degradation in 90S progression.

scholarly journals c-Cbl: An Important Regulator and a Target in Angiogenesis and Tumorigenesis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 498 ◽  
Author(s):  
Chimera L. Lyle ◽  
Mostafa Belghasem ◽  
Vipul C. Chitalia
Keyword(s):  
Therapeutic Potential ◽  
Critical Role ◽  
Modular Function ◽  
Signaling Cascades ◽  
Solid Organ ◽  
Multifunctional Protein ◽  
Ubiquitin E3 Ligase ◽  
Important Regulator ◽  
B Lineage

Casitas B lineage lymphoma (c-Cbl) is a multifunctional protein with a ubiquitin E3 ligase activity capable of degrading diverse sets of proteins. Although previous work had focused mainly on c-Cbl mutations in humans with hematological malignancies, recent emerging evidence suggests a critical role of c-Cbl in angiogenesis and human solid organ tumors. The combination of its unique structure, modular function, and ability to channelize cues from a rich network of signaling cascades, empowers c-Cbl to assume a central role in these disease models. This review consolidates the structural and functional insights based on recent studies that highlight c-Cbl as a target with tantalizing therapeutic potential in various models of angiogenesis and tumorigenesis.

scholarly journals Role of circular RNAs in cardiovascular diseases

2019 ◽  
Vol 244 (2) ◽  
pp. 73-82 ◽  
Author(s):  
Xue Gong ◽  
Gengze Wu ◽  
Chunyu Zeng
Keyword(s):  
Cardiovascular Diseases ◽  
Critical Role ◽  
Developed Countries ◽  
Circular Rnas ◽  
Promising Target ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Expression Abundance ◽  
Therapeutic Perspective

Over the last several decades, cardiovascular diseases largely increase the morbidity and mortality especially in developed countries, affecting millions of people worldwide. Although extensive work over the last two decades attempted to decipher the molecular network of regulating the pathogenesis and progression of these diseases, evidences from clinical trials with newly revealed targets failed to show more evidently salutary effects, indicating the inefficiency of understanding the complete regulatory landscape. Recent studies have shifted their focus from coding genes to the non-coding ones, which consist of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and the lately re-discovered a unique group of RNAs—circular RNAs (circRNAs). As the focus now has been shifted to the newly identified group of non-coding RNAs, circRNAs exhibit stability, highly conservation and relative enriched expression abundance in some cases, which are distinct from their cognate linear counterparts—lncRNAs. So far, emerging evidence begins to support the critical role of circRNAs in organogenesis and pathogenesis as exemplified in the central nervous system, and could be just as implicative in the cardiovascular system, suggesting a therapeutic perspective in related diseases. Impact statement Circular RNAs are important regulators of multiple biological processes such as organogenesis and oncogenesis. Although the bulk of concerning studies focused on revealing their diversified roles in various types of cancers, reports began to accumulate in cardiovascular field these days. We summarize circular RNAs implicated in cardiovascular diseases, aiming to highlight the advances in the knowledge of such diseases and their potential of being promising target for diagnosis and therapy.

Local modes

2002 ◽  
Vol 80 (12) ◽  
pp. 1635-1642 ◽  
Author(s):  
Bryan R Henry ◽  
Henrik G Kjaergaard
Keyword(s):  
Atmospheric Chemistry ◽  
Molecular Conformation ◽  
Critical Role ◽  
Historical Background ◽  
Local Mode ◽  
Local Modes ◽  
Band Profile ◽  
Methyl Rotation ◽  
Insight Into

The historical background for the development of the local mode approach is reviewed, including the critical role of the radiation field. The harmonically coupled anharmonic oscillator model is described. Local modes have been used in the interpretation of XH stretching overtone spectra. These spectra can be used as sensitive probes of molecular properties such as bond length and molecular conformation. Examples of these spectral features are discussed. An intensity theory has been developed that permits the accurate calculation of relative and absolute overtone intensities. In molecules with low barriers to methyl rotation, torsional states contribute to the XH stretching band profile. A successful theoretical approach is presented that accounts for these effects and provides insight into the vibrational dynamics. The application of calculated local mode overtone spectra to atmospheric chemistry is discussed.Key words: local mode, overtone, vibrational intensity.

High-Molecular-Weight, High-Unsaturation Copolymers of Isobutylene and Conjugated Dienes. I. Synthesis

1976 ◽  
Vol 49 (4) ◽  
pp. 960-966 ◽  
Author(s):  
W. A. Thaler ◽  
D. J. Buckley
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Cationic Polymerization ◽  
Critical Role ◽  
Conjugated Dienes ◽  
Solution Properties ◽  
Insight Into

Abstract This investigation has provided insight into the critical role of solution properties on the course of cationic polymerization and has led to a technique for reconciling the opposing demands for synthesis of isoolefin-diene copolymers both free from gel and high in molecular weight. By this technique, the synthesis of a broad range of intermediate-unsaturation elastomers of quality has been realized.

Arbuscular mycorrhizal fungal succession in a long-lived perennial

Botany ◽  
2014 ◽  
Vol 92 (4) ◽  
pp. 313-320 ◽  
Author(s):  
Miranda M. Hart ◽  
Monika Gorzelak ◽  
Diane Ragone ◽  
Susan J. Murch
Keyword(s):  
High Throughput Sequencing ◽  
Selective Pressure ◽  
Arbuscular Mycorrhizal ◽  
Am Fungi ◽  
Fungal Communities ◽  
Artocarpus Altilis ◽  
Host Identity ◽  
Arbuscular Mycorrhizal Fungal ◽  
Insight Into

It is difficult to understand why arbuscular mycorrhizal (AM) fungal communities change over time. The role of host identity confounds our understanding of successional changes in AM fungal communities because hosts exert strong selective pressure on their root-associated microbes. In this study we looked at the AM fungi associated with a long-lived perennial breadfruit (Artocarpus altilis (Parkinson) Fosberg) to see how AM communities change over the life span of a single, long-lived host. Using 454 high-throughput sequencing, we found evidence that older trees had more AM fungal taxa than younger trees and were associated with different AM fungal communities, but these differences were not apparent early in the life cycle. Older trees were dominated by species of Rhizophagus, whereas younger trees and genets were dominated by species of Glomus. Some taxa were only detected in older trees (e.g., Funneliformis) or genets (e.g., Racocetra and Scutellospora), indicating that certain AM fungal taxa may serve as “indicators” of the successional age of the fungal community. These results provide important information about a poorly studied system and give insight into how AM communities change over longer time scales.

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