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Frontiers in Molecular Biosciences

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https://www.readbyqxmd.com/read/30406112/dna-sliding-clamps-as-therapeutic-targets
#1
REVIEW
Amanda S Altieri, Zvi Kelman
Chromosomal DNA replication is achieved by an assembly of multi-protein complexes at the replication fork. DNA sliding clamps play an important role in this assembly and are essential for cell viability. Inhibitors of bacterial (β-clamp) and eukaryal DNA clamps, proliferating cell nuclear antigen (PCNA), have been explored for use as antibacterial and anti-cancer drugs, respectively. Inhibitors for bacterial β-clamps include modified peptides, small molecule inhibitors, natural products, and modified non-steroidal anti-inflammatory drugs...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30406111/the-role-of-pi3k-in-met-driven-cancer-a-recap
#2
REVIEW
Alexia Hervieu, Stéphanie Kermorgant
The Receptor Tyrosine Kinase (RTK) Met, overexpressed or mutated in cancer, plays a major role in cancer progression and represents an attractive target for cancer therapy. However RTK inhibitors can lead to drug resistance, explaining the necessity to develop therapies that target downstream signaling. Phosphatidylinositide 3-kinase (PI3K) is one of the most deregulated pathways in cancer and implicated in various types of cancer. PI3K signaling is also a major signaling pathway downstream of RTK, including Met...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30364190/the-inclusion-of-water-molecules-in-residue-interaction-networks-identifies-additional-central-residues
#3
Guillaume Brysbaert, Ralf Blossey, Marc F Lensink
The relevance of water molecules for the recognition and the interaction of biomolecules is widely appreciated. In this paper we address the role that water molecules associated to protein complexes play for the functional relevance of residues by considering their residue interaction networks (RINs). These are commonly defined on the basis of the amino acid composition of the proteins themselves, disregarding the solvation state of the protein. We determine properties of the RINs of two protein complexes, colicin E2/Im2 and barnase/barstar, with and without associated water molecules, using a previously developed methodology and its associated application RINspector...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30333982/editorial-the-role-of-aaa-proteins-in-protein-repair-and-degradation
#4
EDITORIAL
James Shorter, Walid A Houry
No abstract text is available yet for this article.
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30258844/continuous-immune-cell-differentiation-inferred-from-single-cell-measurements-following-allogeneic-stem-cell-transplantation
#5
Yang Chen, Tadepally Lakshmikanth, Axel Olin, Jaromir Mikes, Mats Remberger, Petter Brodin
The process of immune system regeneration after allogeneic stem cell transplantation is slow, complex, and insufficiently understood. An entire immune system with all of its cell populations must regenerate from infused donor hematopoietic stem cells over the course of weeks and months post-transplantation. Both innate and adaptive arms of the immune system differ in their capacity and speed to reconstitiute in the recipient, which contributes to inadequacy in global immunity during the delayed reconstitution period...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30255025/corrigendum-independent-evolution-of-strychnine-recognition-by-bitter-taste-receptor-subtypes
#6
Ava Yuan Xue, Antonella Di Pizio, Anat Levit, Tali Yarnitzky, Osnat Penn, Tal Pupko, Masha Y Niv
[This corrects the article DOI: 10.3389/fmolb.2018.00009.].
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30246013/the-cancer-spliceome-reprograming-of-alternative-splicing-in-cancer
#7
REVIEW
Ettaib El Marabti, Ihab Younis
Alternative splicing allows for the expression of multiple RNA and protein isoforms from one gene, making it a major contributor to transcriptome and proteome diversification in eukaryotes. Advances in next generation sequencing technologies and genome-wide analyses have recently underscored the fact that the vast majority of multi-exon genes under normal physiology engage in alternative splicing in tissue-specific and developmental-specific manner. On the other hand, cancer cells exhibit remarkable transcriptome alterations partly by adopting cancer-specific splicing isoforms...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30234128/quantification-of-intrinsically-disordered-proteins-a-problem-not-fully-appreciated
#8
Sara Contreras-Martos, Hung H Nguyen, Phuong N Nguyen, Nevena Hristozova, Mauricio Macossay-Castillo, Denes Kovacs, Angela Bekesi, Jesper S Oemig, Dominique Maes, Kris Pauwels, Peter Tompa, Pierre Lebrun
Protein quantification is essential in a great variety of biochemical assays, yet the inherent systematic errors associated with the concentration determination of intrinsically disordered proteins (IDPs) using classical methods are hardly appreciated. Routinely used assays for protein quantification, such as the Bradford assay or ultraviolet absorbance at 280 nm, usually seriously misestimate the concentrations of IDPs due to their distinct and variable amino acid composition. Therefore, dependable method(s) have to be worked out/adopted for this task...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30234127/protocols-for-subtomogram-averaging-of-membrane-proteins-in-the-dynamo-software-package
#9
Paula P Navarro, Henning Stahlberg, Daniel Castaño-Díez
Cryo-electron tomography allows low-resolution three-dimensional (3D) viewing of cellular organelles and macromolecular complexes present as multiple copies within a tomogram. These structures are computationally extracted and averaged in order to obtain high-resolution 3D structures, and provide a map of their spatial distribution and interaction with their biological microenvironment. To do so, we apply the user-friendly Dynamo software package on a tomographic data set. Dynamo acts as a modular toolbox adaptable to different biological scenarios, allowing a custom designed pipeline for subtomogram averaging...
2018: Frontiers in Molecular Biosciences
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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