scholarly journals Fluorescent turn-on probes for wash-free mRNA imaging via covalent site-specific enzymatic labeling

2017 ◽  
Vol 8 (10) ◽  
pp. 7169-7173 ◽  
Author(s):  
Cun Yu Zhou ◽  
Seth C. Alexander ◽  
Neal K. Devaraj
Keyword(s):  
Cellular Regulation ◽  
Site Specific ◽  
Turn On ◽  
The Many ◽  
And Function

Investigating the many roles RNA plays in cellular regulation and function has increased demand for tools to explore RNA tracking and localization within cells.

Centrosome Structure And Function Is Altered By Experimental Manipulations With Formamide: Implications For Abnormal Cell Divisions During Cancer

1999 ◽  
Vol 5 (S2) ◽  
pp. 1286-1287
Author(s):  
Heide Schatten ◽  
Christopher N. Hueser ◽  
Amitabha Chakrabarti
Keyword(s):  
Cell Cycle ◽  
Genomic Stability ◽  
Cellular Regulation ◽  
Mitotic Apparatus ◽  
Abnormal Cell ◽  
Chemical Agents ◽  
Abnormal Mitosis ◽  
And Function ◽  
Normal Mitosis ◽  
Abnormal Cell Proliferation

The formation of abnormal mitosis associated with cancer has been intriguing for many decades. While microtubules had been the focus of previous studies, recent research has focused on centrosomes, microtubule organizing centers which organize the mitotic apparatus during cell division. During normal mitosis centrosomes form two poles but in cancer, centrosomes can form three, four, or more poles, and organize tripolar, quadripolar, and multipolar mitoses, respectively. This has severe consequences for genomic stability because chromosomes are separated unequally to three, four, or more poles. This can result in aneuploidy and gene amplifications with multiple defects in cellular regulation. It can result in malignancy that is accompanied by cell cycle imbalances and abnormal cell proliferation. While radiation and chemical agents are known to damage DNA and can lead to cell cycle abnormalities, the damage of centrosome structure leading to abnormal mitosis deserves also consideration.

scholarly journals Spanning the gap: unraveling RSC dynamics in vivo

2021 ◽  
Author(s):  
Heinz Neumann ◽  
Bryan J. Wilkins
Keyword(s):  
Cell Cycle ◽  
Posttranslational Modifications ◽  
Transcriptional Activation ◽  
Binding Mode ◽  
Binding Modes ◽  
Binding Domains ◽  
Binding Interface ◽  
The Many ◽  
And Function

AbstractMultiple reports over the past 2 years have provided the first complete structural analyses for the essential yeast chromatin remodeler, RSC, providing elaborate molecular details for its engagement with the nucleosome. However, there still remain gaps in resolution, particularly within the many RSC subunits that harbor histone binding domains.Solving contacts at these interfaces is crucial because they are regulated by posttranslational modifications that control remodeler binding modes and function. Modifications are dynamic in nature often corresponding to transcriptional activation states and cell cycle stage, highlighting not only a need for enriched spatial resolution but also temporal understanding of remodeler engagement with the nucleosome. Our recent work sheds light on some of those gaps by exploring the binding interface between the RSC catalytic motor protein, Sth1, and the nucleosome, in the living nucleus. Using genetically encoded photo-activatable amino acids incorporated into histones of living yeast we are able to monitor the nucleosomal binding of RSC, emphasizing the regulatory roles of histone modifications in a spatiotemporal manner. We observe that RSC prefers to bind H2B SUMOylated nucleosomes in vivo and interacts with neighboring nucleosomes via H3K14ac. Additionally, we establish that RSC is constitutively bound to the nucleosome and is not ejected during mitotic chromatin compaction but alters its binding mode as it progresses through the cell cycle. Our data offer a renewed perspective on RSC mechanics under true physiological conditions.

scholarly journals Role of Ubiquitin Ligases and the Proteasome in Oncogenesis: Novel Targets for Anticancer Therapies

2013 ◽  
Vol 31 (9) ◽  
pp. 1231-1238 ◽  
Author(s):  
Lindsey N. Micel ◽  
John J. Tentler ◽  
Peter G. Smith ◽  
Gail S. Eckhardt
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Cell Cycle Control ◽  
Ubiquitin Proteasome System ◽  
Cellular Regulation ◽  
Ubiquitin Chain ◽  
Key Enzyme ◽  
Ubiquitin Proteasome ◽  
Enzyme Families ◽  
And Function

The ubiquitin proteasome system (UPS) regulates the ubiquitination, and thus degradation and turnover, of many proteins vital to cellular regulation and function. The UPS comprises a sequential series of enzymatic processes using four key enzyme families: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-carrier proteins), E3 (ubiquitin-protein ligases), and E4 (ubiquitin chain assembly factors). Because the UPS is a crucial regulator of the cell cycle, and abnormal cell-cycle control can lead to oncogenesis, aberrancies within the UPS pathway can result in a malignant cellular phenotype and thus has become an attractive target for novel anticancer agents. This article will provide an overall review of the mechanics of the UPS, describe aberrancies leading to cancer, and give an overview of current drug therapies selectively targeting the UPS.

THE CRITICALLY ILL CHILD: SICKLE CELL DISEASE CRISES AND THEIR MANAGEMENT

PEDIATRICS ◽  
1971 ◽  
Vol 48 (4) ◽  
pp. 629-635
Author(s):  
Howard A. Pearson ◽  
Louis K. Diamond
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mutant Gene ◽  
Point Of View ◽  
Clinical Aspects ◽  
Cell Disease ◽  
Form And Function ◽  
Heterozygous Form ◽  
The Many ◽  
And Function

This brief review, being limited in scope to the recognition and management of the life-threatening and painful crises in infants and children with sickle-cell disease, has not even touched on the intriguing mystery of the molecular basis for the sickling phenomenon–how one amino-acid substitution (gene controlled) in the beta chain sequence of 146 amino acids can cause such serious disruption in form and function; or how this mutation occurred in the first place and why it has persisted in contrast to the rapid disappearance of many other deleterious mutants. Nor has there been even mention of the many milder symptoms, signs, and complications due to the presence of Hb. S., either in the homozygous (disease-producing) state or heterozygous form when found in combination with other hereditary hemoglobin defects. The accumulated knowledge about this mutant gene, its biochemical effects, and geographic distribution is enormous. From a fundamental scientific standpoint, sickle cell disease is one of the best understood of human afflictions. However, from a practical point of view treatment of the patient himself is often only symptomatic and palliative. Nevertheless, prompt and effective therapy of the myriad manifestations of sickle cell disease can effectively reduce morbidity and mortality. The pediatrician who cares for black children in his practice should be familiar with the cardinal diagnostic and clinical aspects of sickle cell disease and its crises.

scholarly journals Synaptic transmission induces site-specific changes in sialylation on N-linked glycoproteins in rat nerve terminals

2020 ◽  
Author(s):  
Inga Boll ◽  
Pia Jensen ◽  
Veit Schwämmle ◽  
Martin R. Larsen
Keyword(s):  
Synaptic Transmission ◽  
Structure And Function ◽  
Synaptic Proteins ◽  
Nerve Terminals ◽  
Membrane Glycoproteins ◽  
Site Specific ◽  
Specific Alteration ◽  
And Function ◽  
Rat Nerve ◽  
Stimulation Of

AbstractSynaptic transmission leading to release of neurotransmitters in the nervous system is a fast and highly dynamic process. Previously, protein interaction and phosphorylation have been thought to be the main regulators of synaptic transmission. Here we show a novel potential modulator of synaptic transmission, sialylation of N-linked glycosylation. The negatively charged sialic acids can be modulated, similarly to phosphorylation, by the action of sialyltransferases and sialidases thereby changing local structure and function of membrane glycoproteins. We characterized site-specific alteration in sialylation on N-linked glycoproteins in isolated rat nerve terminals after brief depolarization using quantitative sialiomics. We identified 1965 formerly sialylated N-linked glycosites in synaptic proteins and found that the abundances of 430 glycosites changed after five seconds depolarization. We observed changes on essential synaptic proteins such as synaptic vesicle proteins, ion channels and transporters, neurotransmitter receptors and cell adhesion molecules. This study is to our knowledge the first to describe ultra-fast site-specific modulation of the sialiome after brief stimulation of a biological system.

The expanding world of metabolic enzymes moonlighting as RNA binding proteins

2021 ◽  
Author(s):  
Nicole J. Curtis ◽  
Constance J. Jeffery
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Molecular Structures ◽  
Intermediary Metabolism ◽  
The Many ◽  
And Function

RNA binding proteins play key roles in many aspects of RNA metabolism and function, including splicing, transport, translation, localization, stability and degradation. Within the past few years, proteomics studies have identified dozens of enzymes in intermediary metabolism that bind to RNA. The wide occurrence and conservation of RNA binding ability across distant branches of the evolutionary tree suggest that these moonlighting enzymes are involved in connections between intermediary metabolism and gene expression that comprise far more extensive regulatory networks than previously thought. There are many outstanding questions about the molecular structures and mechanisms involved, the effects of these interactions on enzyme and RNA functions, and the factors that regulate the interactions. The effects on RNA function are likely to be wider than regulation of translation, and some enzyme–RNA interactions have been found to regulate the enzyme's catalytic activity. Several enzyme–RNA interactions have been shown to be affected by cellular factors that change under different intracellular and environmental conditions, including concentrations of substrates and cofactors. Understanding the molecular mechanisms involved in the interactions between the enzymes and RNA, the factors involved in regulation, and the effects of the enzyme–RNA interactions on both the enzyme and RNA functions will lead to a better understanding of the role of the many newly identified enzyme–RNA interactions in connecting intermediary metabolism and gene expression.

KAJIAN ORNAMEN GORGA DI RUMAH ADAT BATAK TOBA (Studi Kasus : Di Kawasan Desa Wisata Tomok, Huta Siallagan dan Huta Bolon Di Kabupaten Samosir)

2019 ◽  
Vol 2 (1) ◽  
pp. 1-14
Author(s):  
Dearma A Saragih ◽  
Yulianto Yulianto ◽  
Raimundus Pakpahan
Keyword(s):  
Comparative Research ◽  
Research Method ◽  
Toba Batak ◽  
Historical Heritage ◽  
The Many ◽  
Almost All ◽  
And Function ◽  
Meaning And Function ◽  
House Building

One of the interesting cultural potentials to be studied is traditional houses. This traditional house has its own uniqueness in every area. One of the uniqueness can be seen from the many ornaments in it. Diversity has its own meaning and function. Ornaments is one of the historical heritage of Indonesia where almost all the tribes in Indonesia can be found various kinds of ornaments that reflect the techniques of each region in Indonesia. Ornament Batak Toba is one of the many ornaments that exist in this country Indonesia. Toba Batak ornament can be found in North Sumatera Province precisely in Samosir regency which always apply Toba Batak ornament as decoration or as identity in important building for Batak Toba, for example in traditional house building in Huta Siallagan, Tomok Village and Huta Bolon.This research is classified in research using descriptive-comparative research method, doing the study by comparing the existing ornaments in these three villages with theories about Ornaments Gorga Rumah Adat Batak Toba, then do the analysis of the condition in accordance with the theory used as a reference

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