scholarly journals The Developmental Phases of Zebrafish Myogenesis

2019 ◽  
Vol 7 (2) ◽  
pp. 12 ◽  
Author(s):  
Samuel R. Keenan ◽  
Peter D. Currie
Keyword(s):  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Data Sets ◽  
Vertebrate Lineage ◽  
New Findings ◽  
Muscle Groups ◽  
Teleost Muscle ◽  
Axial Musculature ◽  
Developmental Phases ◽  
Type Specification

The development and growth of vertebrate axial muscle have been studied for decades at both the descriptive and molecular level. The zebrafish has provided an attractive model system for investigating both muscle patterning and growth due to its simple axial musculature with spatially separated fibre types, which contrasts to complex muscle groups often deployed in amniotes. In recent years, new findings have reshaped previous concepts that define how final teleost muscle form is established and maintained. Here, we summarise recent findings in zebrafish embryonic myogenesis with a focus on fibre type specification, followed by an examination of the molecular mechanisms that control muscle growth with emphasis on the role of the dermomyotome-like external cell layer. We also consider these data sets in a comparative context to gain insight into the evolution of axial myogenic patterning systems within the vertebrate lineage.

scholarly journals The Cardiovascular Phenotype in Fabry Disease: New Findings in the Research Field

2021 ◽  
Vol 22 (3) ◽  
pp. 1331
Author(s):  
Daniela Sorriento ◽  
Guido Iaccarino
Keyword(s):  
Fabry Disease ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Research Field ◽  
Cardiac Cell ◽  
Lysosomal Storage ◽  
Clinical Level ◽  
New Findings ◽  
Alpha Gene ◽  
Alpha Galactosidase

Fabry disease (FD) is a lysosomal storage disorder, depending on defects in alpha-galactosidase A (GAL) activity. At the clinical level, FD shows a high phenotype variability. Among them, cardiovascular dysfunction is often recurrent or, in some cases, is the sole symptom (cardiac variant) representing the leading cause of death in Fabry patients. The existing therapies, besides specific symptomatic treatments, are mainly based on the restoration of GAL activity. Indeed, mutations of the galactosidase alpha gene (GLA) cause a reduction or lack of GAL activity leading to globotriaosylceramide (Gb3) accumulation in several organs. However, several other mechanisms are involved in FD’s development and progression that could become useful targets for therapeutics. This review discusses FD’s cardiovascular phenotype and the last findings on molecular mechanisms that accelerate cardiac cell damage.

scholarly journals ETMR-05. SINGLE-CELL RNA-SEQ OF ETMR REVEALS CELL PROGRAMS OF DEVELOPMENTAL HIERARCHY AND CELLULAR DIVERSITY IN THE TUMOR MICROENVIRONMENT

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii323-iii323
Author(s):  
Flavia W de Faria ◽  
Marta Interlandi ◽  
Natalia Moreno ◽  
Monika Graf ◽  
Viktoria Melcher ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Interaction Analysis ◽  
Cellular Heterogeneity ◽  
Receptor Interaction ◽  
Acid Oxidation ◽  
Bmp Receptors ◽  
New Findings ◽  
Developmental Hierarchy

Abstract Embryonal tumors with multilayered rosettes (ETMR) are deadly brain malignancies affecting young children. No standard treatment is available and the median survival is less than 12 months. Molecularly, the disease is characterized by the miRNA C19MC cluster amplification, with the expression of multiples miRNAs related to a stem cell program. The discoveries on the purely molecular mechanisms of the disease did not help to create a bridge for new treatment strategies so far and the cellular diversity of ETMR remains poorly understood. In this study, we used single-cell RNA sequencing of murine and human tumors to describe ETMR cellular heterogeneity. Our findings support that intra-tumoral heterogeneity is mainly characterized by 4 cellular programs defining a developmental hierarchy related to different metabolic states: 1) Early quiescent NSC-like cells supported by fatty-acid oxidation 2) Late NSC and NP-like proliferative cells fueled by glycolytic metabolism; 3) Post-mitotic neuroblast-like cells, relying on oxidative-phosphorylation; 4) NSC-like proliferative cells, with metabolic plasticity and capable of performing the three types of metabolism. Tumor-specific ligand-receptor interaction analysis revealed that ETMR exchange with microglia and vascular mural cells (MC) signals related to extracellular matrix (ECM) organization (Cxcl12-CxCr4), stem cell signaling (BMPs-BMP receptors), anti-apoptosis and survival (Ntf3-Ntrk), not seen in the control brain. In addition, the vascular MC showed a cancer-associated fibroblast (CAF) phenotype, with potential prognostic implications, as previously demonstrated for other tumors. This study provides new findings to build up a more robust understanding of ETMR biology and opens space for further studies in the field.

scholarly journals The migraine–stroke connection: A genetic perspective

Cephalalgia ◽  
2015 ◽  
Vol 36 (7) ◽  
pp. 658-668 ◽  
Author(s):  
Rainer Malik ◽  
Bendik Winsvold ◽  
Eva Auffenberg ◽  
Martin Dichgans ◽  
Tobias Freilinger
Keyword(s):  
Ischemic Stroke ◽  
Vascular Disease ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Familial Hemiplegic Migraine ◽  
Artery Dissection ◽  
Cervical Artery Dissection ◽  
Data Sets ◽  
Genome Wide Association Studies ◽  
Disease Manifestation

Background A complex relationship between migraine and vascular disease has long been recognized. The pathophysiological basis underlying this correlation is incompletely understood. Aim The aim of this review is to focus on the migraine–vascular disorders connection from a genetic perspective, illustrating potentially shared (molecular) mechanisms. Results We first summarize the clinical presentation and genetic basis of CADASIL and other monogenic vascular syndromes with migraine as a prominent disease manifestation. Based on data from transgenic mouse models for familial hemiplegic migraine, we then discuss cortical spreading depression as a potential mechanistic link between migraine and ischemic stroke. Finally, we review data from genome-wide association studies, with a focus on overlapping findings with cervical artery dissection, ischemic stroke in general and cardiovascular disease. Conclusion A wealth of data supports a genetic link between migraine and vascular disease. Based on growing high-throughput data-sets, new genotyping techniques and in-depth phenotyping, further insights are expected for the future.

scholarly journals Quantitative analysis questions the role of MeCP2 as a global regulator of alternative splicing

2020 ◽  
Author(s):  
Kashyap Chhatbar ◽  
Justyna Cholewa-Waclaw ◽  
Ruth Shah ◽  
Adrian Bird ◽  
Guido Sanguinetti
Keyword(s):  
Alternative Splicing ◽  
Dna Sequences ◽  
Molecular Mechanisms ◽  
Data Sets ◽  
Learning Approaches ◽  
Global Regulator ◽  
Major Function ◽  
Quantitative Analyses ◽  
Different Levels

AbstractMeCP2 is an abundant protein in mature nerve cells, where it binds to DNA sequences containing methylated cytosine. Mutations in the MECP2 gene cause the severe neurological disorder Rett syndrome (RTT), provoking intensive study of the underlying molecular mechanisms. Multiple functions have been proposed, one of which involves a regulatory role in splicing. Here we leverage the recent availability of high-quality transcriptomic data sets to probe quantitatively the potential influence of MeCP2 on alternative splicing. Using a variety of machine learning approaches that can capture both linear and non-linear associations, we show that widely different levels of MeCP2 have a minimal effect on alternative splicing in three different systems. Alternative splicing was also apparently indifferent to developmental changes in DNA methylation levels. Our results suggest that regulation of splicing is not a major function of MeCP2. They also highlight the importance of multi-variate quantitative analyses in the formulation of biological hypotheses.

scholarly journals Integrated Physiological and Transcriptomic Analyses Responses to Altitude Stress in Oat (Avena sativa L.)

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Jinqiu ◽  
Li Bing ◽  
Song Tingting ◽  
He Jinglei ◽  
KongLing Zelai ◽  
...  
Keyword(s):  
High Altitude ◽  
Avena Sativa ◽  
Molecular Mechanisms ◽  
Rna Seq ◽  
High Altitudes ◽  
Genome Wide ◽  
New Findings ◽  
Polymerase Chain ◽  
Transcriptomic Changes ◽  
Stressful Environments

Oat is an annual gramineous forage grass with the remarkable ability to survive under various stressful environments. However, understanding the effects of high altitude stresses on oats is poor. Therefore, the physiological and the transcriptomic changes were analyzed at two sites with different altitudes, low (ca. 2,080 m) or high (ca. 2,918 m), respectively. Higher levels of antioxidant enzyme activity, reactive oxygen and major reductions in photosynthesis-related markers were suggested for oats at high altitudes. Furthermore, oat yields were severely suppressed at the high altitude. RNA-seq results showed that 11,639 differentially expressed genes were detected at both the low and the high altitudes in which 5,203 up-regulated and 6,436 down-regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment tests were conducted and a group of major high altitude-responsive pigment metabolism genes, photosynthesis, hormone signaling, and cutin, suberine and wax biosynthesis were excavated. Using quantitative real-time polymerase chain response, we also confirmed expression levels of 20 DEGs (qRT-PCR). In summary, our study generated genome-wide transcript profile and may be useful for understanding the molecular mechanisms of Avena sativa L. in response to high altitude stress. These new findings contribute to our deeper relevant researches on high altitude stresses and further exploring new candidategenes for adapting plateau environment oat molecular breeding.

scholarly journals SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

2018 ◽  
Vol 18 (6) ◽  
pp. 484-493 ◽  
Author(s):  
Xiang Cheng ◽  
Jianying Li ◽  
Deliang Guo
Keyword(s):  
Lipid Metabolism ◽  
Cancer Therapy ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Feedback Regulation ◽  
Negative Feedback Regulation ◽  
Expression Of Genes ◽  
New Findings

Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavageactivating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms. Recent studies have revealed that SREBPs are markedly upregulated in human cancers, providing the mechanistic link between lipid metabolism alterations and malignancies. Pharmacological or genetic inhibition of SCAP or SREBPs significantly suppresses tumor growth in various cancer models, demonstrating that SCAP/SREBPs could serve as promising metabolic targets for cancer therapy. In this review, we will summarize recent progress in our understanding of the underlying molecular mechanisms regulating SCAP/SREBPs and lipid metabolism in malignancies, discuss new findings about SREBP trafficking, which requires SCAP N-glycosylation, and introduce a newly identified microRNA-29-mediated negative feedback regulation of the SCAP/SREBP pathway. Moreover, we will review recently developed inhibitors targeting the SCAP/SREBP pathway for cancer treatment.

scholarly journals Skeletal muscle development in vertebrate animals

2015 ◽  
Vol 1 (2) ◽  
pp. 139-148
Author(s):  
Md Shahjahan
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Muscle Fibers ◽  
Muscle Growth ◽  
Paraxial Mesoderm ◽  
Meat Production ◽  
Lineage Specification ◽  
Proliferation And Differentiation ◽  
Axial Musculature ◽  
Postnatal Stage

This review covers the pre- and post-natal development of skeletal muscle of vertebrate animals with cellular and molecular levels. The formation of skeletal muscle initiates from paraxial mesoderm during embryogenesis of individuals which develops somites and subsequently forms dermomyotome derived myotome to give rise axial musculature. This process (myogenesis) includes stem and progenitor cell maintenance, lineage specification, and terminal differentiation to form myofibrils consequent muscle fibers which control muscle mass and its multiplication. The main factors of muscle growth are proliferation and differentiation of myogenic cells in prenatal stage and also the growth of satellite cells at postnatal stage. There is no net increase in the number of muscle fibers in vertebrate animals after hatch or birth except fish. The development of muscle is characterized by hyperplasia and hypertrophy in prenatal and postnatal stages of individuals, respectively, through Wnt signalling pathway including environment, nutrition, sex, feed, growth and myogenic regulatory factors. Therefore further studies could elucidate new growth related genes, markers and factors to enhance meat production and enrich knowledge on muscle growth.Asian J. Med. Biol. Res. June 2015, 1(2): 139-148

scholarly journals Phylogenetic position and taxonomy of Cycloseris explanulata and C. wellsi (Scleractinia: Fungiidae): lost mushroom corals find their way home

2012 ◽  
Vol 81 (3) ◽  
pp. 125-146 ◽  
Author(s):  
Francesca Benzoni ◽  
Roberto Arrigoni ◽  
Fabrizio Stefani ◽  
Bastian T. Reijnen ◽  
Simone Montano ◽  
...  
Keyword(s):  
Molecular Study ◽  
Molecular Data ◽  
Phylogenetic Position ◽  
Distribution Data ◽  
Data Sets ◽  
Free Living ◽  
New Findings ◽  
The Family ◽  
Ecological Implications ◽  
History Of

The scleractinian species Psammocora explanulata and Coscinaraea wellsi were originally classified in the family Siderastreidae, but in a recent morpho-molecular study it appeared that they are more closely related to each other and to the Fungiidae than to any siderastreid taxon. A subsequent morpho-molecular study of the Fungiidae provided new insights regarding the phylogenetic relationships within that family. In the present study existing molecular data sets of both families were analyzed jointly with those of new specimens and sequences of P. explanulata and C. wellsi. The results indicate that both species actually belong to the Cycloseris clade within the family Fungiidae. A reappraisal of their morphologic characters based on museum specimens and recently collected material substantiate the molecular results. Consequently, they are renamed Cycloseris explanulata and C. wellsi. They are polystomatous and encrusting like C. mokai, another species recently added to the genus, whereas all Cycloseris species were initially thought to be monostomatous and free-living. In the light of the new findings, the taxonomy and distribution data of C. explanulata and C. wellsi have been updated and revised. Finally, the ecological implications of the evolutionary history of the three encrusting polystomatous Cycloseris species and their free-living monostomatous congeners are discussed.

scholarly journals On the Use of Correlation and MI as a Measure of Metabolite—Metabolite Association for Network Differential Connectivity Analysis

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 171
Author(s):  
Sanjeevan Jahagirdar ◽  
Edoardo Saccenti
Keyword(s):  
Molecular Mechanisms ◽  
Real Life ◽  
Simulated Data ◽  
Metabolic Model ◽  
Data Sets ◽  
Connectivity Analysis ◽  
Estimation Algorithms ◽  
Metabolomic Data ◽  
Spearman’S Correlation ◽  
Differential Connectivity

Metabolite differential connectivity analysis has been successful in investigating potential molecular mechanisms underlying different conditions in biological systems. Correlation and Mutual Information (MI) are two of the most common measures to quantify association and for building metabolite—metabolite association networks and to calculate differential connectivity. In this study, we investigated the performance of correlation and MI to identify significantly differentially connected metabolites. These association measures were compared on (i) 23 publicly available metabolomic data sets and 7 data sets from other fields, (ii) simulated data with known correlation structures, and (iii) data generated using a dynamic metabolic model to simulate real-life observed metabolite concentration profiles. In all cases, we found more differentially connected metabolites when using correlation indices as a measure for association than MI. We also observed that different MI estimation algorithms resulted in difference in performance when applied to data generated using a dynamic model. We concluded that there is no significant benefit in using MI as a replacement for standard Pearson’s or Spearman’s correlation when the application is to quantify and detect differentially connected metabolites.

scholarly journals A20: a master regulator of arthritis

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongyao Wu ◽  
Xiaomin He ◽  
Ning Huang ◽  
Jiayun Yu ◽  
Bin Shao
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Mouse Models ◽  
Inflammatory Arthritis ◽  
Molecular Mechanisms ◽  
Related Research ◽  
Inflammatory Protein ◽  
New Findings ◽  
Tnf Α

Abstract A20, also known as TNF-α-induced protein 3 (TNFAIP3), is an anti-inflammatory protein that plays an important part in both immune responses and cell death. Impaired A20 function is associated with several human inflammatory and autoimmune diseases. Although the role of A20 in mediating inflammation has been frequently discussed, its intrinsic link to arthritis awaits further explanation. Here, we review new findings that further demonstrate the molecular mechanisms through which A20 regulates inflammatory arthritis, and we discuss the regulation of A20 by many factors. We conclude by reviewing the latest A20-associated mouse models that have been applied in related research because they reflect the characteristics of arthritis, the study of which will hopefully cast new light on anti-arthritis treatments.

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