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Frontiers in Molecular Biosciences

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https://www.readbyqxmd.com/read/30214903/systematic-analysis-of-gene-expression-profiles-controlled-by-hnrnp-q-and-hnrnp-r-two-closely-related-human-rna-binding-proteins-implicated-in-mrna-processing-mechanisms
#1
Sara Cappelli, Maurizio Romano, Emanuele Buratti
Heteregeneous ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins that take part in all processes that involve mRNA maturation. As a consequence, alterations of their homeostasis may lead to many complex pathological disorders, such as neurodegeneration and cancer. For many of these proteins, however, their exact function and cellular targets are still not very well known. Here, we focused the attention on two hnRNP family members, hnRNP Q and hnRNP R, that we previously found affecting TDP-43 activity both in Drosophila melanogaster and human neuronal cell line...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30211170/engagement-rules-that-underpin-dbl-darc-interactions-for-ingress-of-plasmodium-knowlesi-and-plasmodium-vivax-into-human-erythrocytes
#2
REVIEW
Manickam Yogavel, Jyoti Chhibber-Goel, Abhishek Jamwal, Swati Gupta, Amit Sharma
Malaria parasite erythrocytic stages comprise of repeated bursts of parasites via cyclical invasion of host erythrocytes using dedicated receptor-ligand interactions. A family of erythrocyte-binding proteins from Plasmodium knowlesi ( Pk ) and Plasmodium vivax ( Pv ) attach to human Duffy antigen receptor for chemokines (DARC) via their Duffy binding-like domains (DBLs) for invasion. Here we provide a novel, testable and overarching interaction model that rationalizes even contradictory pieces of evidence that have so far existed in the literature on Pk / Pv -DBL/DARC binding determinants...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30211169/molecular-diagnostics-in-clinical-oncology
#3
REVIEW
Anna P Sokolenko, Evgeny N Imyanitov
There are multiple applications of molecular tests in clinical oncology. Mutation analysis is now routinely utilized for the diagnosis of hereditary cancer syndromes. Healthy carriers of cancer-predisposing mutations benefit from tight medical surveillance and various preventive interventions. Cancers caused by germ-line mutations often require significant modification of the treatment strategy. Personalized selection of cancer drugs based on the presence of actionable mutations has become an integral part of cancer therapy...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30197885/activation-of-the-calcium-sensing-receptor-corrects-the-impaired-mitochondrial-energy-status-observed-in-renal-polycystin-1-knockdown-cells-modeling-autosomal-dominant-polycystic-kidney-disease
#4
Annarita Di Mise, Marianna Ranieri, Mariangela Centrone, Maria Venneri, Grazia Tamma, Daniela Valenti, Giovanna Valenti
Autosomal Dominant Polycistic kidney Disease (ADPKD) is a renal channelopathy due to loss-of-function mutations in the PKD1 or PKD2 genes, encoding polycystin-1 (PC1) or polycystin-2 (PC2), respectively. PC1 is a large protein found predominantly on the plasma membrane where interacts with different proteins, including PC2. PC2 is a smaller integral membrane protein also expressed in intracellular organelles, acting as a non-selective cation channel permeable to calcium. Both PC1 and PC2 are also localized to the primary cilium of renal epithelial cells serving as mechanosensor that controls calcium influx through the plasma membrane and regulates intracellular calcium release from the endoplasmic reticulum...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30155470/extracellular-atp-regulates-cd73-and-abcc6-expression-in-hepg2-cells
#5
Fabio Martinelli, Flavia Cuviello, Maria C Pace, Maria F Armentano, Rocchina Miglionico, Angela Ostuni, Faustino Bisaccia
The ATP-binding cassette sub-family C member 6 transporter (ABCC6) is an ATP dependent transporter mainly found in the basolateral plasma membrane of hepatic and kidney cells. Mutations in ABCC6 gene were associated to the Pseudoxanthoma elasticum (PXE), an autosomal recessive disease characterized by a progressive ectopic calcification of elastic fibers in dermal, ocular, and vascular tissues. It is reported that the over-expression of ABCC6 in HEK293 cells results in the cellular efflux of ATP and other nucleoside triphosphates, which in turn are rapidly converted into nucleoside monophosphates and pyrophosphate (PPi)...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30155469/trp-channels-as-potential-targets-for-sex-related-differences-in-migraine-pain
#6
REVIEW
Maite Artero-Morales, Sara González-Rodríguez, Antonio Ferrer-Montiel
Chronic pain is one of the most debilitating human diseases and represents a social and economic burden for our society. Great efforts are being made to understand the molecular and cellular mechanisms underlying the pathophysiology of pain transduction. It is particularly noteworthy that some types of chronic pain, such as migraine, display a remarkable sex dimorphism, being up to three times more prevalent in women than in men. This gender prevalence in migraine appears to be related to sex differences arising from both gonadal and genetic factors...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30131964/cryo-em-grid-preparation-of-membrane-protein-samples-for-single-particle-analysis
#7
REVIEW
Germán G Sgro, Tiago R D Costa
Recent advances in cryo-electron microscopy (cryo-EM) have made it possible to solve structures of biological macromolecules at near atomic resolution. Development of more stable microscopes, improved direct electron detectors and faster software for image processing has enabled structural solution of not only large macromolecular (megadalton range) complexes but also small (~60 kDa) proteins. As a result of the widespread use of the technique, we have also witnessed new developments of techniques for cryo-EM grid preparation of membrane protein samples...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30131963/editorial-type-i-chaperonins-mechanism-and-beyond
#8
EDITORIAL
Adina Breiman, Abdussalam Azem
No abstract text is available yet for this article.
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30109234/network-architecture-and-mutational-sensitivity-of-the-c-elegans-metabolome
#9
Lindsay M Johnson, Luke M Chandler, Sarah K Davies, Charles F Baer
A fundamental issue in evolutionary systems biology is understanding the relationship between the topological architecture of a biological network, such as a metabolic network, and the evolution of the network. The rate at which an element in a metabolic network accumulates genetic variation via new mutations depends on both the size of the mutational target it presents and its robustness to mutational perturbation. Quantifying the relationship between topological properties of network elements and the mutability of those elements will facilitate understanding the variation in and evolution of networks at the level of populations and higher taxa...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30094239/structural-components-for-amplification-of-positive-and-negative-strand-veev-splitzicons
#10
Anna K Blakney, Paul F McKay, Robin J Shattock
RNA is a promising nucleic acid technology for both vaccines and therapeutics, and replicon RNA has gained traction as a next-generation RNA modality. Replicon RNA self-amplifies using a replicase complex derived from alphaviral non-structural proteins and yields higher protein expression than a similar dose of messenger RNA. Here, we debut RNA splitzicons; a split replicon system wherein the non-structural proteins (NSPs) and the gene of interest are encoded on separate RNA molecules, but still exhibit the self-amplification properties of replicon RNA...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30094238/precision-medicine-for-neonatal-sepsis
#11
REVIEW
Sherrianne Ng, Tobias Strunk, Pingping Jiang, Tik Muk, Per T Sangild, Andrew Currie
Neonatal sepsis remains a significant cause of morbidity and mortality especially in the preterm infant population. The ability to promptly and accurately diagnose neonatal sepsis based on clinical evaluation and laboratory blood tests remains challenging. Advances in high-throughput molecular technologies have increased investigations into the utility of transcriptomic, proteomic and metabolomic approaches as diagnostic tools for neonatal sepsis. A systems-level understanding of neonatal sepsis, obtained by using omics-based technologies (at the transcriptome, proteome or metabolome level), may lead to new diagnostic tools for neonatal sepsis...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30094237/insect-arylalkylamine-n-acyltransferases-mechanism-and-role-in-fatty-acid-amide-biosynthesis
#12
REVIEW
Brian G O'Flynn, Gabriela Suarez, Aidan J Hawley, David J Merkler
Arylalkylamine N -acyltransferases (AANATs) catalyze the formation of an N -acylamide from an acyl-CoA thioester and an amine. One well known example is the production of N -acetylserotonin from acetyl-CoA and serotonin, a reaction in the melatonin biosynthetic pathway from tryptophan. AANATs have been identified from a variety of vertebrates and invertebrates. Considerable efforts have been devoted to the mammalian AANAT because a cell-permeable inhibitor specifically targeted against this enzyme could prove useful to treat diseases related to dysfunction in melatonin production...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30090811/fumarase-from-the-tca-cycle-to-dna-damage-response-and-tumor-suppression
#13
REVIEW
Michael Leshets, Yardena B H Silas, Norbert Lehming, Ophry Pines
Fumarase is an enzyme of the tricarboxylic acid (TCA) cycle in mitochondria, but in recent years, it has emerged as a participant in the response to DNA double strand breaks (DSBs) in the nucleus. In fact, this enzyme is dual-targeted and can be also readily detected in the mitochondrial and cytosolic/nuclear compartments of all the eukaryotic organisms examined. Intriguingly, this evolutionary conserved cytosolic population of fumarase, its enzymatic activity and the associated metabolite fumarate, are required for the cellular DNA damage response (DDR) to double-strand breaks...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30073169/lps-induces-mtorc1-and-mtorc2-activation-during-monocyte-adhesion
#14
Marcelle C Ribeiro, Diogo B Peruchetti, Leandro S Silva, João L Silva-Filho, Mariana C Souza, Maria das Graças Henriques, Celso Caruso-Neves, Ana Acacia S Pinheiro
Monocyte adhesion is a crucial step in transmigration and can be induced by lipopolysaccharide (LPS). Here, we studied the role of mammalian target of rapamycin (mTOR) complexes, mTORC1 and mTORC2, and PKC in this process. We used THP-1 cells, a human monocytic cell line, to investigate monocyte adhesion under static and flow conditions. We observed that 1.0 μg/mL LPS increased PI3K/mTORC2 pathway and PKC activity after 1 h of incubation. WYE-354 10-6 M (mTORC2/mTORC1 inhibitor) and 10-6 M wortmannin avoided monocyte adhesion in culture plates...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30057902/how-does-solvation-layer-mobility-affect-protein-structural-dynamics
#15
Jayangika N Dahanayake, Katie R Mitchell-Koch
Solvation is critical for protein structural dynamics. Spectroscopic studies have indicated relationships between protein and solvent dynamics, and rates of gas binding to heme proteins in aqueous solution were previously observed to depend inversely on solution viscosity. In this work, the solvent-compatible enzyme Candida antarctica lipase B, which functions in aqueous and organic solvents, was modeled using molecular dynamics simulations. Data was obtained for the enzyme in acetonitrile, cyclohexane, n- butanol, and tert- butanol, in addition to water...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30057901/3-rna-uridylation-in-epitranscriptomics-gene-regulation-and-disease
#16
REVIEW
Miriam R Menezes, Julien Balzeau, John P Hagan
Emerging evidence implicates a wide range of post-transcriptional RNA modifications that play crucial roles in fundamental biological processes including regulating gene expression. Collectively, they are known as epitranscriptomics. Recent studies implicate 3' RNA uridylation, the non-templated addition of uridine(s) to the terminal end of RNA, as a key player in epitranscriptomics. In this review, we describe the functional roles and significance of 3' terminal RNA uridylation that has diverse functions in regulating both mRNAs and non-coding RNAs...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30042949/the-impairment-of-torsina-s-binding-to-and-interactions-with-its-activator-an-atomistic-molecular-dynamics-study-of-primary-dystonia
#17
Emmanuel O Salawu
Primary dystonia's prolonged muscle contractions and the associated abnormal postures and twisting movements remain incurable. Genetic mutation/deletion of GAG from TorsonA's gene resulting in ΔE303 (which weakens the binding between TorsinA and its activator, such as LULL1) primarily cause this neurodegenerative disorder. We studied TorsinA-LULL1 (or TorsinAΔE303-LULL1) bindings and interactions. For the first time, we show the atomic details of TorsinA-LULL1 dynamic interactions and TorsinAΔE303-LULL1 dynamic interactions and their binding affinities...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30038906/possible-mechanisms-by-which-enzymatic-degradation-of-human-serum-albumin-can-lead-to-bioactive-peptides-and-biomarkers
#18
Ulrich Kragh-Hansen
Partial enzymatic degradation of human serum albumin in vivo can lead to the generation of peptides with novel functions or to peptides that might serve as biomarkers for disease. In pathological conditions, biomarkers are possibly produced from the protein in the lysosomes and set free by cell death, or cell death could release acid endoproteases which produce biomarkers by degrading extracellular albumin. Alternatively, lysosomes or secretory granules can be stimulated to release enzymes which produce bioactive peptides from albumin...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30027092/high-quality-de-novo-transcriptome-assembly-of-croton-tiglium
#19
Markus Haak, Svenja Vinke, Willy Keller, Julian Droste, Christian Rückert, Jörn Kalinowski, Boas Pucker
No abstract text is available yet for this article.
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30018958/structural-and-functional-insights-into-lysostaphin-substrate-interaction
#20
Helena Tossavainen, Vytas Raulinaitis, Linda Kauppinen, Ulla Pentikäinen, Hannu Maaheimo, Perttu Permi
Lysostaphin from Staphylococcus simulans and its family enzymes rapidly acquire prominence as the next generation agents in treatment of S. aureus infections. The specificity of lysostaphin is promoted by its C-terminal cell wall targeting domain selectivity toward pentaglycine bridges in S. aureus cell wall. Scission of these cross-links is carried out by its N-terminal catalytic domain, a zinc-dependent endopeptidase. Understanding the determinants affecting the efficiency of catalysis and strength and specificity of interactions lies at the heart of all lysostaphin family enzyme applications...
2018: Frontiers in Molecular Biosciences
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