scholarly journals MiR-9 and the Midbrain-Hindbrain Boundary: A Showcase for the Limited Functional Conservation and Regulatory Complexity of MicroRNAs

2020 ◽  
Vol 8 ◽  
Author(s):  
A. Alwin Prem Anand ◽  
Gonzalo Alvarez-Bolado ◽  
Andrea Wizenmann
Keyword(s):  
Neuronal Development ◽  
Brain Size ◽  
Regulatory System ◽  
Large Degree ◽  
Regulate Gene Expression ◽  
Functional Conservation ◽  
Regulatory Complexity ◽  
Species Specific ◽  
And Function

MicroRNAs regulate gene expression at post-transcriptional levels. Some of them appear to regulate brain development and are involved in neurodevelopmental disorders. This has led to the suggestion that the role of microRNAs in neuronal development and function may be more central than previously appreciated. Here, we review the data about miR-9 function to depict the subtlety, complexity, flexibility and limited functional conservation of this essential developmental regulatory system. On this basis we propose that species-specific actions of miR-9 could underlie to a large degree species differences in brain size, shape and function.

scholarly journals Equine Drug Transporters: A Mini-Review and Veterinary Perspective

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1064
Author(s):  
Brielle Rosa
Keyword(s):  
Drug Transport ◽  
Drug Disposition ◽  
Drug Transporters ◽  
Transport Proteins ◽  
Pharmacokinetic Parameters ◽  
Transporter Protein ◽  
Drug Pharmacokinetic ◽  
Species Specific ◽  
And Function

Xenobiotic transport proteins play an important role in determining drug disposition and pharmacokinetics. Our understanding of the role of these important proteins in humans and pre-clinical animal species has increased substantially over the past few decades, and has had an important impact on human medicine; however, veterinary medicine has not benefitted from the same quantity of research into drug transporters in species of veterinary interest. Differences in transporter expression cause difficulties in extrapolation of drug pharmacokinetic parameters between species, and lack of knowledge of species-specific transporter distribution and function can lead to drug–drug interactions and adverse effects. Horses are one species in which little is known about drug transport and transporter protein expression. The purpose of this mini-review is to stimulate interest in equine drug transport proteins and comparative transporter physiology.

scholarly journals Duplication and functional divergence of a calcium sensor in the Brassicaceae

2020 ◽  
Vol 71 (9) ◽  
pp. 2782-2795 ◽  
Author(s):  
Shea M Monihan ◽  
Courtney A Magness ◽  
Choong-Hwan Ryu ◽  
Michelle M McMahon ◽  
Mark A Beilstein ◽  
...  
Keyword(s):  
Salt Tolerance ◽  
Functional Divergence ◽  
Calcium Sensor ◽  
The Family ◽  
Salt Affected Soils ◽  
Species Specific ◽  
And Function ◽  
Sisymbrium Irio ◽  
Functional Analyses

Abstract The presence of varied numbers of CALCINEURIN B-LIKE10 (CBL10) calcium sensor genes in species across the Brassicaceae and the demonstrated role of CBL10 in salt tolerance in Arabidopsis thaliana and Eutrema salsugineum provided a unique opportunity to determine if CBL10 function is modified in different species and linked to salt tolerance. Salinity effects on species growth and cross-species complementation were used to determine the extent of conservation and divergence of CBL10 function in four species representing major lineages within the core Brassicaceae (A. thaliana, E. salsugineum, Schrenkiella parvula, and Sisymbrium irio) as well as the first diverging lineage (Aethionema arabicum). Evolutionary and functional analyses indicate that CBL10 duplicated within expanded lineage II of the Brassicaceae and that, while portions of CBL10 function are conserved across the family, there are species-specific variations in CBL10 function. Paralogous CBL10 genes within a species diverged in expression and function probably contributing to the maintenance of the duplicated gene pairs. Orthologous CBL10 genes diverged in function in a species-specific manner, suggesting that functions arose post-speciation. Multiple CBL10 genes and their functional divergence may have expanded calcium-mediated signaling responses and contributed to the ability of certain members of the Brassicaceae to maintain growth in salt-affected soils.

scholarly journals Regulation of Breast Cancer and Bone Metastasis by MicroRNAs

2013 ◽  
Vol 35 ◽  
pp. 369-387 ◽  
Author(s):  
S. Vimalraj ◽  
P. J. Miranda ◽  
B. Ramyakrishna ◽  
N. Selvamurugan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Bone Metastasis ◽  
Cancer Progression ◽  
Human Breast ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Complex Process ◽  
And Function

Breast cancer progression including bone metastasis is a complex process involving numerous changes in gene expression and function. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate gene expression by targeting protein-coding mRNAs posttranscriptionally, often affecting a number of gene targets simultaneously. Alteration in expression of miRNAs is common in human breast cancer, possessing with either oncogenic or tumor suppressive activity. The expression and the functional role of several miRNAs (miR-206, miR-31, miR-27a/b, miR-21, miR-92a, miR-205, miR-125a/b, miR-10b, miR-155, miR-146a/b, miR-335, miR-204, miR-211, miR-7, miR-22, miR-126, and miR-17) in breast cancer has been identified. In this review we summarize the experimentally validated targets of up- and downregulated miRNAs and their regulation in breast cancer and bone metastasis for diagnostic and therapeutic purposes.

scholarly journals Role of PPARγin the Differentiation and Function of Neurons

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Rodrigo A. Quintanilla ◽  
Elias Utreras ◽  
Fabián A. Cabezas-Opazo
Keyword(s):  
Neuropathic Pain ◽  
Neurodegenerative Disorders ◽  
Neuronal Death ◽  
Neuronal Development ◽  
Brain Cells ◽  
Neuronal Processes ◽  
And Function ◽  
Pain Regulation ◽  
Important Evidence

Neuronal processes (neurites and axons) have an important role in brain cells communication and, generally, they are damaged in neurodegenerative diseases. Recent evidence has showed that the activation of PPARγpathway promoted neuronal differentiation and axon polarity. In addition, activation of PPARγusing thiazolidinediones (TZDs) prevented neurodegeneration by reducing neuronal death, improving mitochondrial function, and decreasing neuroinflammation in neuropathic pain. In this review, we will discuss important evidence that supports a possible role of PPARγin neuronal development, improvement of neuronal health, and pain signaling. Therefore, activation of PPARγis a potential target with therapeutic applications against neurodegenerative disorders, brain injury, and pain regulation.

scholarly journals The yeast SWI-SNF complex facilitates binding of a transcriptional activator to nucleosomal sites in vivo.

1997 ◽  
Vol 17 (8) ◽  
pp. 4811-4819 ◽  
Author(s):  
L G Burns ◽  
C L Peterson
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Protein Assembly ◽  
Transcriptional Activators ◽  
Regulate Gene Expression ◽  
Activation Of Transcription ◽  
Free Region ◽  
And Function

The Saccharomyces cerevisiae SWI-SNF complex is a 2-MDa protein assembly that is required for the function of many transcriptional activators. Here we describe experiments on the role of the SWI-SNF complex in activation of transcription by the yeast activator GAL4. We find that while SWI-SNF activity is not required for the GAL4 activator to bind to and activate transcription from nucleosome-free binding sites, the complex is required for GAL4 to bind to and function at low-affinity, nucleosomal binding sites in vivo. This SWI-SNF dependence can be overcome by (i) replacing the low-affinity sites with higher-affinity, consensus GAL4 binding sequences or (ii) placing the low-affinity sites into a nucleosome-free region. These results define the criteria for the SWI-SNF dependence of gene expression and provide the first in vivo evidence that the SWI-SNF complex can regulate gene expression by modulating the DNA binding of an upstream activator protein.

scholarly journals MicroRNAs in the skin: role in development, homoeostasis and regeneration

2017 ◽  
Vol 131 (15) ◽  
pp. 1923-1940 ◽  
Author(s):  
Steven Horsburgh ◽  
Nicola Fullard ◽  
Mathilde Roger ◽  
Abbie Degnan ◽  
Stephen Todryk ◽  
...  
Keyword(s):  
Therapeutic Interventions ◽  
Transcriptional Gene Silencing ◽  
Biological Functions ◽  
Vast Number ◽  
Regulate Gene Expression ◽  
Post Transcriptional Gene Silencing ◽  
Non Coding Rnas ◽  
And Function ◽  
Molecular Signals

The skin is the largest organ of the integumentary system and possesses a vast number of functions. Due to the distinct layers of the skin and the variety of cells which populate each, a tightly regulated network of molecular signals control development and regeneration, whether due to programmed cell termination or injury. MicroRNAs (miRs) are a relatively recent discovery; they are a class of small non-coding RNAs which possess a multitude of biological functions due to their ability to regulate gene expression via post-transcriptional gene silencing. Of interest, is that a plethora of data demonstrates that a number of miRs are highly expressed within the skin, and are evidently key regulators of numerous vital processes to maintain non-aberrant functioning. Recently, miRs have been targeted as therapeutic interventions due to the ability of synthetic ‘antagomiRs’ to down-regulate abnormal miR expression, thereby potentiating wound healing and attenuating fibrotic processes which can contribute to disease such as systemic sclerosis (SSc). This review will provide an introduction to the structure and function of the skin and miR biogenesis, before summarizing the literature pertaining to the role of miRs. Finally, miR therapies will also be discussed, highlighting important future areas of research.

scholarly journals Interspecies Variations in Bordetella Catecholamine Receptor Gene Regulation and Function

2015 ◽  
Vol 83 (12) ◽  
pp. 4639-4652 ◽  
Author(s):  
Timothy J. Brickman ◽  
Ryan J. Suhadolc ◽  
Sandra K. Armstrong
Keyword(s):  
Receptor Gene ◽  
Regulatory System ◽  
Outer Membrane Receptor ◽  
Iron Starvation ◽  
Content Type ◽  
Receptor Proteins ◽  
And Function ◽  
Iron Receptor

Bordetella bronchisepticacan use catecholamines to obtain iron from transferrin and lactoferrin via uptake pathways involving the BfrA, BfrD, and BfrE outer membrane receptor proteins, and althoughBordetella pertussishas thebfrDandbfrEgenes, the role of these genes in iron uptake has not been demonstrated. In this study, thebfrDandbfrEgenes ofB. pertussiswere shown to be functional inB. bronchiseptica, but neitherB. bronchiseptica bfrDnorbfrEimparted catecholamine utilization toB. pertussis. Gene fusion analyses found that expression ofB. bronchiseptica bfrAwas increased during iron starvation, as is common for iron receptor genes, but that expression of thebfrDandbfrEgenes of both species was decreased during iron limitation. As shown previously forB. pertussis,bfrDexpression inB. bronchisepticawas also dependent on the BvgAS virulence regulatory system; however, in contrast to the case inB. pertussis, the known modulators nicotinic acid and sulfate, which silence Bvg-activated genes, did not silence expression ofbfrDinB. bronchiseptica. Further studies using aB. bronchisepticabvgASmutant expressing theB. pertussisbvgASgenes revealed that the interspecies differences inbfrDmodulation are partly due to BvgAS differences. Mouse respiratory infection experiments determined that catecholamine utilization contributes to thein vivofitness ofB. bronchisepticaandB. pertussis. Additional evidence of thein vivoimportance of theB. pertussisreceptors was obtained from serologic studies demonstrating pertussis patient serum reactivity with theB. pertussisBfrD and BfrE proteins.

scholarly journals The Effects of Leptin Replacement on Neural Plasticity

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Gilberto J. Paz-Filho
Keyword(s):  
Neural Plasticity ◽  
Observational Studies ◽  
Neuronal Development ◽  
Neuronal Morphology ◽  
Synaptic Activity ◽  
Hypothalamic Amenorrhea ◽  
Glutamate Receptor Trafficking ◽  
Brain Structure And Function ◽  
And Function

Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function.

scholarly journals Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders

2019 ◽  
Vol 20 (21) ◽  
pp. 5477 ◽  
Author(s):  
Eleonora D’Ambra ◽  
Davide Capauto ◽  
Mariangela Morlando
Keyword(s):  
Nervous System ◽  
Neuronal Development ◽  
Circular Rnas ◽  
Pathological Conditions ◽  
Exact Function ◽  
Modulation Of Gene Expression ◽  
Development And Aging ◽  
And Function ◽  
Regulatory Functions

Circular RNAs (circRNAs) are a distinctive class of regulatory non-coding RNAs characterised by the presence of covalently closed ends. They are evolutionary conserved molecules, and although detected in different tissues, circRNAs resulted specifically enriched in the nervous system. Recent studies have shown that circRNAs are dynamically modulated during neuronal development and aging, that circRNAs are enriched at synaptic levels and resulted modulated after synaptic plasticity induction. This has suggested that circRNAs might play an important role in neuronal specification and activity. Despite the exact function of circRNAs is still poorly understood, emerging evidence indicates that circRNAs have important regulatory functions that might extensively contribute to the dynamic modulation of gene expression that supports neuronal pathways. More interestingly, deregulation of circRNAs expression has been linked with various pathological conditions. In this review, we describe current advances in the field of circRNA biogenesis and function in the nervous system both in physiological and in pathological conditions, and we specifically lay out their association with neurodegenerative diseases. Furthermore, we discuss the opportunity to exploit circRNAs for innovative therapeutic approaches and, due to their high stability, to use circRNAs as suitable biomarkers for diagnosis and disease progression.

scholarly journals Role of the imprinted allele of the p57Kip2 gene in mouse neocortical development

2019 ◽  
Author(s):  
Yui Imaizumi ◽  
Shohei Furutachi ◽  
Tomoyuki Watanabe ◽  
Hiroaki Miya ◽  
Daichi Kawaguchi ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Brain Size ◽  
Paternal Allele ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Conditional Deletion ◽  
Neocortical Development ◽  
Neural Stem Progenitor Cells ◽  
The Central Nervous System ◽  
And Function

AbstractImprinted genes are expressed from only one allele in a parent of origin–specific manner. The cyclin-dependent kinase inhibitor p57Kip2 (p57) is encoded by an imprinted gene, with the paternal allele being silenced. The possible expression and function of the paternal allele of p57 have remained little studied, however. We now show that the paternal allele of the p57 gene is expressed at a low level in the developing mouse neocortex. Surprisingly, the central nervous system-specific conditional deletion of the paternal allele (pat cKO) at the p57 locus resulted in a marked reduction in brain size. Furthermore, pat cKO gradually reduced the number of neural stem-progenitor cells (NPCs) during neocortical development, and thus reduced the number of upper-layer neurons, which were derived from late-stage NPCs. Our results thus show that the paternal allele of the p57 locus plays a key role in maintenance of NPCs during neocortical development.

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