scholarly journals MicroRNAs and Cardiovascular Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Tsuyoshi Nishiguchi ◽  
Toshio Imanishi ◽  
Takashi Akasaka
Keyword(s):  
Messenger Rna ◽  
Plaque Rupture ◽  
Large Fraction ◽  
Rna Sequences ◽  
Posttranscriptional Gene Silencing ◽  
Rna Molecules ◽  
Endothelium Dysfunction ◽  
Near Future ◽  
Made In

Coronary artery diseases (CAD) and heart failure have high mortality rate in the world, although much progress has been made in this field in last two decades. There is still a clinical need for a novel diagnostic approach and a therapeutic strategy to decrease the incidence of CAD. MicroRNAs (miRNAs) are highly conserved noncoding small RNA molecules that regulate a large fraction of the genome by binding to complementary messenger RNA sequences, resulting in posttranscriptional gene silencing. Recent studies have shown that specific miRNAs are involved in whole stage of atherosclerosis, from endothelium dysfunction to plaque rupture. These findings suggest that miRNAs are potential biomarkers in early diagnosis and therapeutic targets in CAD. In the present review, we highlight the role of miRNAs in every stage of atherosclerosis, and discuss the prospects of miRNAs in the near future.

scholarly journals Simultaneity and Precise Time in Rotation

Universe ◽  
2019 ◽  
Vol 5 (12) ◽  
pp. 226 ◽  
Author(s):  
Don Koks
Keyword(s):  
Time Coordinate ◽  
Near Future ◽  
Precise Time ◽  
Made In

I analyse the role of simultaneity in relativistic rotation by building incrementally on its role in simpler scenarios. Historically, rotation has been analysed in 1 + 1 dimensions; but my stance is that a 2 + 1 -dimensional treatment is necessary. This treatment requires a discussion of what constitutes a frame, how coordinate choices differ from frame choices, and how poor coordinates can be misleading. I determine how precisely we are able to define a meaningful time coordinate on a gravity-free rotating Earth, and discuss complications due to gravity on our real Earth. I end with a critique of several statements made in relativistic precision-timing literature, that I maintain contradict the tenets of relativity. Those statements tend to be made in the context of satellite-based navigation; but they are independent of that technology, and hence are not validated by its success. I suggest that if relativistic precision-timing adheres to such analyses, our civilian timing is likely to suffer in the near future as clocks become ever more precise.

scholarly journals Transcriptome-wide analysis of PGC-1α–binding RNAs identifies genes linked to glucagon metabolic action

2020 ◽  
Vol 117 (36) ◽  
pp. 22204-22213 ◽  
Author(s):  
Clint D. J. Tavares ◽  
Stefan Aigner ◽  
Kfir Sharabi ◽  
Shashank Sathe ◽  
Beste Mutlu ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Large Fraction ◽  
Glucose Production ◽  
Peroxisome Proliferator ◽  
Rna Sequences ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rna Recognition Motifs ◽  
Transcript Levels ◽  
Recognition Motifs ◽  
Metabolic Action

The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a transcriptional coactivator that controls expression of metabolic/energetic genes, programming cellular responses to nutrient and environmental adaptations such as fasting, cold, or exercise. Unlike other coactivators, PGC-1α contains protein domains involved in RNA regulation such as serine/arginine (SR) and RNA recognition motifs (RRMs). However, the RNA targets of PGC-1α and how they pertain to metabolism are unknown. To address this, we performed enhanced ultraviolet (UV) cross-linking and immunoprecipitation followed by sequencing (eCLIP-seq) in primary hepatocytes induced with glucagon. A large fraction of RNAs bound to PGC-1α were intronic sequences of genes involved in transcriptional, signaling, or metabolic function linked to glucagon and fasting responses, but were not the canonical direct transcriptional PGC-1α targets such as OXPHOS or gluconeogenic genes. Among the top-scoring RNA sequences bound to PGC-1α wereFoxo1,Camk1δ,Per1,Klf15,Pln4,Cluh,Trpc5,Gfra1, andSlc25a25. PGC-1α depletion decreased a fraction of these glucagon-induced messenger RNA (mRNA) transcript levels. Importantly, knockdown of several of these genes affected glucagon-dependent glucose production, a PGC-1α–regulated metabolic pathway. These studies show that PGC-1α binds to intronic RNA sequences, some of them controlling transcript levels associated with glucagon action.

scholarly journals 178 Continuing to enhance efficiency in swine

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 183-183
Author(s):  
Graham Plastow
Keyword(s):  
New Technologies ◽  
Significant Proportion ◽  
Swine Production ◽  
Live Animal ◽  
Enhance Efficiency ◽  
Market Needs ◽  
The Impact ◽  
Near Future ◽  
Made In

Abstract Efficiency in swine production is made up of a number of traits including reproduction, health, and the conversion of feed into pork. Due to the large proportion of cost associated with feed (>70% of overall costs) there has been a focus on this aspect of efficiency. Indeed, significant progress has been made in reducing the amount of feed required to reach market weight. This has been achieved at the same time as increasing growth rate (and therefore decreasing age at slaughter) whilst maintaining carcass quality to meet market needs. A significant proportion of this improvement was delivered through genetics and the application of new measurement technologies. Examples, include the use of ultrasound to measure fat content on the live animal and individual feed intake recording. At a time when sustainable production is increasingly demanded then efficiency will continue to be important through its impact on the economics of farming – productivity and profit. However, sustainability takes into account other aspects such as the impact on the environment as well as social aspects such as animal welfare. Many of these components support each other, for example, more prolific sows producing more efficient full market value pigs contribute to a smaller environmental footprint (more product and less waste). Likewise pigs that stay healthy even when responding to infection continue to eat and require less medication. When antagonisms exist they can be addressed in a balanced selection program that addresses all aspects. We are now at a point where new technologies will make it feasible to address these additional factors providing the opportunity for even greater progress in these key traits in the near future. This presentation will provide examples of the progress made and the role of genomics in utilizing “big data” to continue to improve the efficiency of swine production.

scholarly journals Membrane-bound ribosomes of myeloma cells. III. The role of the messenger RNA and the nascent polypeptide chain in the binding of ribosomes to membranes.

1975 ◽  
Vol 67 (1) ◽  
pp. 25-37 ◽  
Author(s):  
B Mechler ◽  
P Vassalli
Keyword(s):  
Protein Synthesis ◽  
Messenger Rna ◽  
Membrane Fraction ◽  
Polypeptide Chain ◽  
Salt Treatment ◽  
Ribosomal Subunits ◽  
Myeloma Cells ◽  
Membrane Bound ◽  
Made In

Mild ribonuclease treatment of the membrane fraction of P3K cells released three types of membrane-bound ribosomal particles: (a) all the newly made native 40S subunits detected after 2 h of [3H]uridine pulse. Since after a 3-min pulse with [35S]methionine these membrane native subunits appear to contain at least sevenfold more Met-tRNA per particle than the free native subunits, they may all be initiation complexes with mRNA molecules which have just become associated with the membranes; (b) about 50% of the ribosomes present in polyribosomes. Evidence is presented that the released ribosomes carry nascent chains about two and a half to three times shorter than those present on the ribosomes remaining bound to the membranes. It is proposed that in the membrane-bound polyribosomes of P3K cells, only the ribosomes closer to the 3' end of the mRNA molecules are directly bound, while the latest ribosomes to enter the polyribosomal structures are indirectly bound through the mRNA molecules; (c) a small number of 40S subunits of polyribosomal origin, presumably initiation complexes attached at the 5' end of mRNA molecules of polyribosomes. When the P3K cells were incubated with inhibitors acting at different steps of protein synthesis, it was found that puromycin and pactamycin decreased by about 40% the proportion of ribosomes in the membrane fraction, while cycloheximide and anisomycin had no such effect. The ribosomes remaining on the membrane fraction of puromycin-treated cells consisted of a few polyribosomes, and of an accumulation of 80S and 60S particles, which were almost entirely released by high salt treatment of the membranes. The membrane-bound ribosomes found after pactamycin treatment consisted of a few polyribosomes, with a striking accumulation of native 60S subunits and an increased number of native 40S subunits. On the basis of the observations made in this and the preceding papers, a model for the binding of ribosomes to membranes and for the ribosomal cycle on the membranes is proposed. It is suggested that ribosomal subunits exchange between free and membrane-bound polyribosomes through the cytoplasmic pool of free native subunits, and that their entry into membrane-bound ribosomes is mediated by mRNA molecules associated with membranes.

Phenotypic Traits and Regulatory Role of RNA Folding in Molecular Selection

1991 ◽  
Vol 46 (7-8) ◽  
pp. 656-662
Author(s):  
Ariel Fernández
Keyword(s):  
Rna Folding ◽  
De Novo ◽  
Phenotypic Expression ◽  
Regulatory Role ◽  
Phenotypic Traits ◽  
Intermediate Structure ◽  
Rna Sequences ◽  
Rna Molecules ◽  
Molecular Selection

Abstract We concentrate on instances in which the phenotypic expression of information encoded in an RNA primary sequence might be revealed by the folding of the RNA itself. We have discov­ered that this situation finds concrete realization in the design of RNA molecules capable of maximizing the rate of autocatalytic synthesis when incubated with viral Qβ-replicase. This requires that we introduce the notion of phenotypic traits at the molecular level. Thus, the problem of finding RNA sequences whose phenotype favorably influences propagation amounts to finding RNA sequences which fold so as to optimize enzymatic performance and are in addition endowed with the proper recognition sites. The proof that these two problems are indeed equivalent has two steps: First we predict the metastable folded structures formed as a template RNA chain grows by sequential incorporation of nucleotides. The transient folded states appear to be involved in the regulation of the enzyme activity and they occur in a manner which is “oblivious” of thermodynamic time scales. Secondly, we compute the time-dependent activation energy for relaxation of each intermediate structure. This is done to establish constraints necessary for optimization of the regulatory role of RNA folding. The search for prospective template sequences is subject to such constraints. Our results aim at elucidating an optimization process realized by molecular selection in de novo (template-free) RNA synthesis by Qβ-replicase. We argue that the phenotype which mediates selection is given by metastable folding which emerges together with the printing of the genotype, that is, within the time span of a replication turnover.

scholarly journals MicroRNAs as Biomarkers and Therapeutic Targets in Heart Failure

2019 ◽  
Vol 65 (3) ◽  
pp. 77-79
Author(s):  
István Adorján Szabó ◽  
Atilla Frigy
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Messenger Rna ◽  
Short Review ◽  
Rna Molecules ◽  
Functional Changes ◽  
Diagnosis And Prognosis ◽  
Adaptive Processes ◽  
Altered Gene

AbstractHeart failure still represents a real challenge both in everyday practice and research, due to the complex issues related to its pathogenesis and management. Humoral biomarkers have emerged in the last decades as useful tools in the diagnosis, risk stratification and guiding the treatment of heart failure. These molecules are related to different pathological and adaptive processes, like myocardial injury, neurohormonal activation and cardiac remodeling, their most widespread representatives being the natriuretic peptides (e.g. NT-proBNP). The role of altered gene expression and transcription as the basis of myocardial structural and functional changes in heart failure is largely recognized. MicroRNAs (miRNAs) are non-coding RNAs which have a major role in post-transcriptional gene expression by interfering with messenger RNA molecules. Our short review summarizes the molecular biology of miRNAs and their possible role as biomarkers in the diagnosis and prognosis of heart failure. Furthermore, the therapeutical perspectives conferred by these molecules are also presented.

scholarly journals Demonstration of Balbiani ring RNA sequences in polysomes.

1977 ◽  
Vol 73 (1) ◽  
pp. 260-264 ◽  
Author(s):  
L Wieslander ◽  
B Daneholt
Keyword(s):  
In Situ Hybridization ◽  
Messenger Rna ◽  
Sucrose Gradient ◽  
Balbiani Ring ◽  
Rna Sequences ◽  
Rna Molecules ◽  
Labeled Rna ◽  
Active Genes

A polysome extract from salivary glands of C. tentans was sedimented in a 15-60% sucrose gradient. Fractions from the heavy polysome region (1,000-2,000S) and fractions from the light polysome region (200-1,000S) were pooled separately, and the long-term labeled RNA was released by Sarkosyl/pronase and analysed by in situ hybridization. The results showed that BR 1 and BR 2 sequences were present in the heavy and the light polysome regions of the sucrose gradient. From control experiments with EDTA-treated extracts, it was concluded that most of the recorded BR 1 and BR 2 sequences were in fact located in polysomes. The finding that BR products enter polysomes suggests that they act as messenger RNA molecules. This study therefore strongly supports the concept that chromosome puffs represent active genes.

scholarly journals  The structure and role of mammalian sperm RNA: a review

2013 ◽  
Vol 58 (No. 2) ◽  
pp. 57-64 ◽  
Author(s):  
D. Bukowska ◽  
B. Kempisty ◽  
H. Piotrowska ◽  
P. Sosinska ◽  
M. Wozna ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Early Embryo ◽  
Main Role ◽  
Messenger Rnas ◽  
Paternal Genome ◽  
Rna Molecules ◽  
Integral Role ◽  
Complex Population ◽  
Chromatin Organisation

The main role of sperm is the delivery of the paternal genome into the oocyte during fertilisation. However, several lines of evidence have indicated that mammalian spermatozoa contribute more than just their DNA, namely, they also deliver a large range of RNA molecules. Microarray analysis has revealed a complex population of 3000 different kinds of messenger RNA that are delivered to oocytes by sperm and ejaculated spermatozoa are estimated to contain about 0.015 pg of total RNA. Some of the transcripts encode proteins crucial for early embryo development. Messenger RNAs from sperm also help to protect the paternal genes, which have an integral role soon after fertilisation. The molecular participation of the oocyte during fertilisation is well understood but the function of the sperm in this process remains unclear. During spermatogenesis the structure of the male haploid genome is permanently modified. Transition proteins (TNPs), protamines (PRMs) and histones (HILS-spermatid specific linker histone) play a unique role in spermatid chromatin compaction. In this review, the structure and role of sperm RNA as well as chromatin organisation during spermatogenesis are discussed.  

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

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