scholarly journals Phosphatidic acid – a simple phospholipid with multiple faces

2018 ◽  
Vol 65 (2) ◽  
pp. 163-171 ◽  
Author(s):  
Jolanta Zegarlinska ◽  
Magda Piaścik ◽  
Aleksander F Sikorski ◽  
Aleksander Czogalla
Keyword(s):  
Phosphatidic Acid ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Large Degree ◽  
Cellular Lipids ◽  
Living Organisms ◽  
Protein Recruitment ◽  
Membrane Shape

Phosphatidic acid (PA) is the simplest glycerophospholipid naturally occurring in living organisms, and even though its content among other cellular lipids is minor, it is drawing more and more attention due to its multiple biological functions. PA is a precursor for other phospholipids, acts as a lipid second messenger and, due to its structural properties, is also a modulator of membrane shape. Although much is known about interaction of PA with its effectors, the molecular mechanisms remain unresolved to a large degree. Throughout many of the well-characterized PA cellular sensors, no conserved binding domain can be recognized. Moreover, not much is known about the cellular dynamics of PA and how it is distributed among subcellular compartments. Remarkably, PA can play distinct roles within each of these compartments. For example, in the nucleus it behaves as a mitogen, influencing gene expression regulation, and in the Golgi membrane it plays a role in membrane trafficking. Here we discuss how a biophysical experimental approach enabled PA behavior to be described in the context of a lipid bilayer and to what extent various physicochemical conditions may modulate the functional properties of the lipid. Understanding these aspects would help to unravel specific mechanisms of PA-driven membrane transformation and protein recruitment and thus would lead to a clearer picture of the biological role of PA.

scholarly journals ARPEGGIO: Automated Reproducible Polyploid EpiGenetic GuIdance workflOw

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Stefan Milosavljevic ◽  
Tony Kuo ◽  
Samuele Decarli ◽  
Lucas Mohn ◽  
Jun Sese ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Sequence Similarity ◽  
Ground Truth ◽  
Whole Genome ◽  
Initial Dataset ◽  
Quality Checks ◽  
Living Organisms ◽  
Set Up

Abstract Background Whole genome duplication (WGD) events are common in the evolutionary history of many living organisms. For decades, researchers have been trying to understand the genetic and epigenetic impact of WGD and its underlying molecular mechanisms. Particular attention was given to allopolyploid study systems, species resulting from an hybridization event accompanied by WGD. Investigating the mechanisms behind the survival of a newly formed allopolyploid highlighted the key role of DNA methylation. With the improvement of high-throughput methods, such as whole genome bisulfite sequencing (WGBS), an opportunity opened to further understand the role of DNA methylation at a larger scale and higher resolution. However, only a few studies have applied WGBS to allopolyploids, which might be due to lack of genomic resources combined with a burdensome data analysis process. To overcome these problems, we developed the Automated Reproducible Polyploid EpiGenetic GuIdance workflOw (ARPEGGIO): the first workflow for the analysis of epigenetic data in polyploids. This workflow analyzes WGBS data from allopolyploid species via the genome assemblies of the allopolyploid’s parent species. ARPEGGIO utilizes an updated read classification algorithm (EAGLE-RC), to tackle the challenge of sequence similarity amongst parental genomes. ARPEGGIO offers automation, but more importantly, a complete set of analyses including spot checks starting from raw WGBS data: quality checks, trimming, alignment, methylation extraction, statistical analyses and downstream analyses. A full run of ARPEGGIO outputs a list of genes showing differential methylation. ARPEGGIO was made simple to set up, run and interpret, and its implementation ensures reproducibility by including both package management and containerization. Results We evaluated ARPEGGIO in two ways. First, we tested EAGLE-RC’s performance with publicly available datasets given a ground truth, and we show that EAGLE-RC decreases the error rate by 3 to 4 times compared to standard approaches. Second, using the same initial dataset, we show agreement between ARPEGGIO’s output and published results. Compared to other similar workflows, ARPEGGIO is the only one supporting polyploid data. Conclusions The goal of ARPEGGIO is to promote, support and improve polyploid research with a reproducible and automated set of analyses in a convenient implementation. ARPEGGIO is available at https://github.com/supermaxiste/ARPEGGIO.

scholarly journals Effect of Surface Roughness on Aggregation of Polypeptide Chains: A Monte Carlo Study

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 596
Author(s):  
Nguyen Truong Co ◽  
Mai Suan Li
Keyword(s):  
Surface Roughness ◽  
Self Assembly ◽  
Molecular Mechanisms ◽  
Monte Carlo Study ◽  
The Self ◽  
Living Organisms ◽  
Polypeptide Chains ◽  
The Impact ◽  
Kinetics Of

The self-assembly of amyloidogenic peptides and proteins into fibrillar structures has been intensively studied for several decades, because it seems to be associated with a number of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. Therefore, understanding the molecular mechanisms of this phenomenon is important for identifying an effective therapy for the corresponding diseases. Protein aggregation in living organisms very often takes place on surfaces like membranes and the impact of a surface on this process depends not only on the surface chemistry but also on its topology. Our goal was to develop a simple lattice model for studying the role of surface roughness in the aggregation kinetics of polypeptide chains and the morphology of aggregates. We showed that, consistent with the experiment, an increase in roughness slows down the fibril formation, and this process becomes inhibited at a very highly level of roughness. We predicted a subtle catalytic effect that a slightly rough surface promotes the self-assembly of polypeptide chains but does not delay it. This effect occurs when the interaction between the surface and polypeptide chains is moderate and can be explained by taking into account the competition between energy and entropy factors.

scholarly journals The Role of lncRNAs in Gene Expression Regulation through mRNA Stabilization

2021 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Maialen Sebastian-delaCruz ◽  
Itziar Gonzalez-Moro ◽  
Ane Olazagoitia-Garmendia ◽  
Ainara Castellanos-Rubio ◽  
Izortze Santin
Keyword(s):  
Gene Expression ◽  
Mrna Stability ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Mrna Stabilization ◽  
Living Organisms ◽  
Almost All

mRNA stability influences gene expression and translation in almost all living organisms, and the levels of mRNA molecules in the cell are determined by a balance between production and decay. Maintaining an accurate balance is crucial for the correct function of a wide variety of biological processes and to maintain an appropriate cellular homeostasis. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of gene expression through different molecular mechanisms, including mRNA stabilization. In this review we provide an overview on the molecular mechanisms by which lncRNAs modulate mRNA stability and decay. We focus on how lncRNAs interact with RNA binding proteins and microRNAs to avoid mRNA degradation, and also on how lncRNAs modulate epitranscriptomic marks that directly impact on mRNA stability.

scholarly journals The role of traction in membrane curvature generation

2017 ◽  
Author(s):  
H. Alimohamadi ◽  
R. Vasan ◽  
J.E. Hassinger ◽  
J.C. Stachowiak ◽  
P. Rangamani
Keyword(s):  
Molecular Mechanisms ◽  
Unit Length ◽  
Line Tension ◽  
Membrane Curvature ◽  
Local Shape ◽  
Sources Of Uncertainty ◽  
Protein Scaffolding ◽  
Membrane Deformations ◽  
Membrane Shape

AbstractCurvature of biological membranes can be generated by a variety of molecular mechanisms including protein scaffolding, compositional heterogeneity, and cytoskeletal forces. These mechanisms have the net effect of generating tractions (force per unit length) on the bilayer that are translated into distinct shapes of the membrane. Here, we demonstrate how the local shape of the membrane can be used to infer the traction acting locally on the membrane. We show that buds and tubes, two common membrane deformations studied in trafficking processes, have different traction distributions along the membrane and that these tractions are specific to the molecular mechanism used to generate these shapes. Furthermore, we show that the magnitude of an axial force applied to the membrane as well as that of an effective line tension can be calculated from these tractions. Finally, we consider the sensitivity of these quantities with respect to uncertainties in material properties and follow with a discussion on sources of uncertainty in membrane shape.

scholarly journals Multidrug Resistance in Breast Cancer: FromIn VitroModels to Clinical Studies

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
N. S. Wind ◽  
I. Holen
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Abc Transporters ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Large Degree ◽  
Model Systems ◽  
Chemotherapy Drugs ◽  
Response To Chemotherapy

The development of multidrug resistance (MDR) and subsequent relapse on therapy is a widespread problem in breast cancer, but our understanding of the underlying molecular mechanisms is incomplete. Numerous studies have aimed to establish the role of drug transporter pumps in MDR and to link their expression to response to chemotherapy. The ATP-binding cassette (ABC) transporters are central to breast cancer MDR, and increases in ABC expression levels have been shown to correlate with decreases in response to various chemotherapy drugs and a reduction in overall survival. But as there is a large degree of redundancy between different ABC transporters, this correlation has not been seen in all studies. This paper provides an introduction to the key molecules associated with breast cancer MDR and summarises evidence of their potential roles reported from model systems and clinical studies. We provide possible explanations for why despite several decades of research, the precise role of ABC transporters in breast cancer MDR remains elusive.

scholarly journals Structure and activity of the Saccharomyces cerevisiae dUTP pyrophosphatase DUT1, an essential housekeeping enzyme

2011 ◽  
Vol 437 (2) ◽  
pp. 243-253 ◽  
Author(s):  
Anatoli Tchigvintsev ◽  
Alexander U. Singer ◽  
Robert Flick ◽  
Pierre Petit ◽  
Greg Brown ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Mechanisms ◽  
Site Directed Mutagenesis ◽  
Saturation Curve ◽  
Significant Activity ◽  
Active Site Residues ◽  
Living Organisms ◽  
Hydrolysis Of

Genomes of all free-living organisms encode the enzyme dUTPase (dUTP pyrophosphatase), which plays a key role in preventing uracil incorporation into DNA. In the present paper, we describe the biochemical and structural characterization of DUT1 (Saccharomyces cerevisiae dUTPase). The hydrolysis of dUTP by DUT1 was strictly dependent on a bivalent metal cation with significant activity observed in the presence of Mg2+, Co2+, Mn2+, Ni2+ or Zn2+. In addition, DUT1 showed a significant activity against another potentially mutagenic nucleotide: dITP. With both substrates, DUT1 demonstrated a sigmoidal saturation curve, suggesting a positive co-operativity between the subunits. The crystal structure of DUT1 was solved at 2 Å resolution (1 Å=0.1 nm) in an apo state and in complex with the non-hydrolysable substrate α,β-imido dUTP or dUMP product. Alanine-replacement mutagenesis of the active-site residues revealed seven residues important for activity including the conserved triad Asp87/Arg137/Asp85. The Y88A mutant protein was equally active against both dUTP and UTP, indicating that this conserved tyrosine residue is responsible for discrimination against ribonucleotides. The structure of DUT1 and site-directed mutagenesis support a role of the conserved Phe142 in the interaction with the uracil base. Our work provides further insight into the molecular mechanisms of substrate selectivity and catalysis of dUTPases.

scholarly journals Learning about microbial language: possible interactions mediated by microbial volatile organic compounds (VOCs) and relevance to understanding Malassezia spp. metabolism

Metabolomics ◽  
2021 ◽  
Vol 17 (4) ◽  
Author(s):  
Andrea Rios-Navarro ◽  
Mabel Gonzalez ◽  
Chiara Carazzone ◽  
Adriana Marcela Celis Ramírez
Keyword(s):  
Volatile Organic Compounds ◽  
Organic Compounds ◽  
Molecular Mechanisms ◽  
Host Interaction ◽  
Interaction Processes ◽  
Volatile Organic ◽  
Microbial Volatile Organic Compounds ◽  
Living Organisms ◽  
Malassezia Spp

Abstract Background Microorganisms synthesize and release a large diversity of small molecules like volatile compounds, which allow them to relate and interact with their environment. Volatile organic compounds (VOCs) are carbon-based compounds with low molecular weight and generally, high vapor pressure; because of their nature, they spread easily in the environment. Little is known about the role of VOCs in the interaction processes, and less is known about VOCs produced by Malassezia, a genus of yeasts that belongs to the human skin mycobiota. These yeasts have been associated with several dermatological diseases and currently, they are considered as emerging opportunistic yeasts. Research about secondary metabolites of these yeasts is limited. The pathogenic role and the molecular mechanisms involved in the infection processes of this genus are yet to be clarified. VOCs produced by Malassezia yeasts could play an important function in their metabolism; in addition, they might be involved in either beneficial or pathogenic host-interaction processes. Since these yeasts present differences in their nutritional requirements, like lipids to grow, it is possible that these variations of growth requirements also define differences in the volatile organic compounds produced in Malassezia species. Aim of review We present a mini review about VOCs produced by microorganisms and Malassezia species, and hypothesize about their role in its metabolism, which would reveal clues about host-pathogen interaction. Key scientific concepts of review Since living organisms inhabit a similar environment, the interaction processes occur naturally; as a result, a signal and a response from participants of these processes become important in understanding several biological behaviors. The efforts to elucidate how living organisms interact has been studied from several perspectives. An important issue is that VOCs released by the microbiota plays a key role in the setup of relationships between living micro and macro organisms. The challenge is to determine what is the role of these VOCs produced by human microbiota in commensal/pathogenic scenarios, and how these allow understanding the species metabolism. Malassezia is part of the human mycobiota, and it is implicated in commensal and pathogenic processes. It is possible that their VOCs are involved in these behavioral changes, but the knowledge about this remains overlocked. For this reason, VOCs produced by microorganisms and Malassezia spp. and their role in several biological processes are the main topic in this review.

scholarly journals ARPEGGIO: Automated Reproducible Polyploid EpiGenetic GuIdance workflOw

2020 ◽  
Author(s):  
Stefan Milosavljevic ◽  
Tony Kuo ◽  
Samuele Decarli ◽  
Lucas Mohn ◽  
Jun Sese ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Sequence Similarity ◽  
Implementation Strategies ◽  
Ground Truth ◽  
Ease Of Use ◽  
Whole Genome ◽  
Quality Checks ◽  
Living Organisms

AbstractWhole genome duplication (WGD) events are common in the evolutionary history of many living organisms. For decades, researchers have been trying to understand the genetic and epigenetic impact of WGD and its underlying molecular mechanisms. Particular attention was given to allopolyploid study systems, species resulting from an hybridization event accompanied by WGD. Investigating the mechanisms behind the survival of a newly formed allopolyploid highlighted the key role of DNA methylation. With the improvement of high-throughput methods, such as whole genome bisulfite sequencing (WGBS), an opportunity opened to further understand the role of DNA methylation at a larger scale and higher resolution. However, only a few studies have applied WGBS to allopolyploids, which might be due to lack of genomic resources combined with a burdensome data analysis process. To overcome these problems, we developed the Automated Reproducible Polyploid EpiGenetic GuIdance workflOw (ARPEGGIO): the first workflow for the analysis of epigenetic data in polyploids. This workflow analyzes WGBS data from allopolyploid species via the genome assemblies of the allopolyploid’s parent species. ARPEGGIO utilizes an updated read classification algorithm (EAGLE-RC), to tackle the challenge of sequence similarity amongst parental genomes. ARPEGGIO offers automation, but more importantly, a complete set of analyses including spot checks starting from raw WGBS data: quality checks, trimming, alignment, methylation extraction, statistical analyses and downstream analyses. A full run of ARPEGGIO outputs a list of genes showing differential methylation. ARPEGGIO’s design focuses on ease of use and reproducibility. ARPEGGIO was made simple to set up, run and interpret, and its implementation includes both package management and containerization. Here we discuss all the steps, challenges and implementation strategies; example datasets are provided to show how to use ARPEGGIO. In addition, we also test EAGLE-RC with publicly available datasets given a ground truth, and we show that EAGLE-RC decreases the error rate by 3 to 4 times compared to standard approaches. The goal of ARPEGGIO is to promote, support and improve polyploid research with a reproducible and automated set of analyses in a convenient implementation.

scholarly journals The Endosomal Recycling Pathway—At the Crossroads of the Cell

2020 ◽  
Vol 21 (17) ◽  
pp. 6074
Author(s):  
Mary J. O’Sullivan ◽  
Andrew J. Lindsay
Keyword(s):  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Human Pathogens ◽  
Transport Pathways ◽  
Endosomal Recycling ◽  
Wide Range ◽  
Secretory Transport ◽  
Recycling Pathway

The endosomal recycling pathway lies at the heart of the membrane trafficking machinery in the cell. It plays a central role in determining the composition of the plasma membrane and is thus critical for normal cellular homeostasis. However, defective endosomal recycling has been linked to a wide range of diseases, including cancer and some of the most common neurological disorders. It is also frequently subverted by many diverse human pathogens in order to successfully infect cells. Despite its importance, endosomal recycling remains relatively understudied in comparison to the endocytic and secretory transport pathways. A greater understanding of the molecular mechanisms that support transport through the endosomal recycling pathway will provide deeper insights into the pathophysiology of disease and will likely identify new approaches for their detection and treatment. This review will provide an overview of the normal physiological role of the endosomal recycling pathway, describe the consequences when it malfunctions, and discuss potential strategies for modulating its activity.

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