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Frontiers in the Pharmacological Manipulation of Intracellular cAMP Levels

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198153 Year: Pages: 191 DOI: 10.3389/978-2-88919-815-3 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Cyclic adenosine monophosphate (cAMP) is a second messenger of paramount biological importance, involved in the regulation of a significant number of cellular functions through the cAMP-dependent intracellular signal transduction pathways. The aim of this "Frontiers in Pharmacology" Research Topic was to attract contributions that highlight emerging ideas in the cAMP field that: (i) describe its role in cellular function and homeostasis, (ii) present the current approaches to its pharmacological manipulation, and (iii) clarify its central role in the development of more targeted therapeutic approaches toward a spectrum of diseases. The present collection of articles highlights, in a representative (but certainly not exhaustive) way, the research activity and emerging concepts in the field, while it also reveals the therapeutic potential that targeted pharmacological manipulation of intracellular cAMP levels could exert on a number of pathological conditions.

Frontiers of Sulfur Metabolism in Plant Growth, Development, and Stress Response

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199037 Year: Pages: 368 DOI: 10.3389/978-2-88919-903-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany
Added to DOAB on : 2016-01-19 14:05:46
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Growing plants have a constitutive demand for sulfur to synthesize proteins, sulfolipids and other essential sulfur containing molecules for growth and development. The uptake and subsequent distribution of sulfate is regulated in response to demand and environmental cues. The importance of sulfate for plant growth and vigor and hence crop yield and nutritional quality for human and animal diets has been clearly recognized. The acquisition of sulfur by plants, however, has become an increasingly important concern for the agriculture due to the decreasing S-emissions from industrial sources and the consequent limitation of inputs from atmospheric deposition. Molecular characterization involving transcriptomics, proteomics and metabolomics in Arabidopsis thaliana as well as in major crops revealed that sulfate uptake, distribution and assimilation are finely regulated depending on sulfur status and demand, and that these regulatory networks are integrated with cell cycle, photosynthesis, carbohydrate metabolism, hormonal signaling, uptake and assimilation of other nutrients, etc., to enable plant growth, development, and reproduction even under different biotic and abiotic stresses. This knowledge can be used to underpin approaches to enhance plant growth and nutritional quality of major food crops around the world. Although considerable progress has been made regarding the central role of sulfur metabolism in plant growth, development and stress response, several frontiers need to be explored to reveal the mechanisms of the cross-talk between sulfur metabolism and these processes. In this research topic the knowledge on plant sulfur metabolism is reviewed and updated. Focus is put not only on molecular mechanisms of control of sulfur metabolism but also on its integration with other vital metabolic events. The topic covers 4 major areas of sulfur research: sulfate uptake, assimilation and metabolism, regulation, and role in stress response. We hope that the topic will promote interaction between researchers with different expertise and thus contribute to a more integrative approach to study sulfur metabolism in plants.

Extracellular Nucleotides in the Regulation of Kidney Functions

Authors: --- --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195046 Year: Pages: 77 DOI: 10.3389/978-2-88919-504-6 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2015-12-03 13:02:24
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ATP is normally regarded as the major source of fuel for the energy-demanding processes within cells; however, ATP and other nucleotides (such as ADP, UTP, UDP) can be released from cells, where they act as autocrine or paracrine signaling molecules to affect cellular and tissue functions. In response to various stimuli, ATP and other nucleotides are released from cells in a regulated fashion, either by exocytosis of nucleotide-containing vesicles, or through channels in the plasma membrane. This process occurs in virtually every organ or cell in the body. The cellular effects of these extracellular nucleotides are mediated through specific membrane receptors (P2X and P2Y). These nucleotide signals can be terminated by rapid degradation of the ligand molecules by ecto-nucleotidases (e.g., NTPDases and NPPs). Many of the molecular components essential to nucleotide signaling have been cloned and characterized in detail, and their crystal structures are beginning to emerge. The collected data on extracellular nucleotides suggest a vivid and dynamic signaling system that is modulated by the expression and sensitivity of specific receptors on cells, and by the regulated release and extracellular degradation of ATP and other nucleotides; thus creating a microenvironment of highly regulated paracrine or autocrine control mechanisms. Within the kidney, extracellular nucleotides have emerged as potent modulators of glomerular, tubular, and microvascular functions. These functions include, but are not limited to, tubular transport of water and sodium, tubuloglomerular feedback and auto-regulation, regulation of blood pressure and the microcirculation, oxidative stress, and cell proliferation/ necrosis/apoptosis. Moreover, studies have also uncovered the interaction of nucleotide signaling with other mediators of renal function, such as vasopressin, aldosterone, nitric oxide, prostaglandins, angiotensin II, and the ATP-break down product adenosine. These insights have provided a more comprehensive and cohesive picture of the role of extracellular nucleotides in the regulation of renal function in health and disease. The availability of transgenic mouse models of the key proteins involved in nucleotide signaling has markedly enhanced our understanding of the physiological and pathophysiological roles of the different components of the system in the kidney. Although at a preliminary stage, the pathophysiological significance of this system in the kidney holds the key for the development of an entirely new class of drugs for the treatment of disease conditions, including disorders of water and/or sodium homeostasis, hypertension, acute kidney injury, etc. Thus, the regulation of renal function by extracellular nucleotides is clearly emerging as a distinct field and discipline in renal physiology and pathophysiology that has the potential to develop new drug treatments. In this e-book, we bring together a spectrum of excellent papers by leading experts in the field which present and discuss the latest developments and state-of-the-art technologies.Last but not least, we thank all the authors for contributing their valuable work and the Frontiers in Physiology Editorial Office for bringing out this e-book.

Molecular Modeling in Drug Design

Authors: ---
ISBN: 9783038976141 Year: Pages: 220 DOI: 10.3390/books978-3-03897-615-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Chemistry (General) --- Science (General)
Added to DOAB on : 2019-04-05 10:34:31
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Abstract

This book is a printed edition of the Special Issue Molecular Modeling in Drug Design that was published in Molecules

Keywords

hyperlipidemia --- squalene synthase (SQS) --- molecular modeling --- drug discovery --- Traditional Chinese Medicine --- molecular dynamics simulation --- biophenols --- natural compounds --- amyloid fibrils --- Alzheimer’s disease --- ligand–protofiber interactions --- adhesion --- FimH --- rational drug design --- molecular dynamics --- molecular docking --- ligand binding --- EphA2-ephrin A1 --- PPI inhibition --- interaction energy --- in silico screening --- adenosine --- boron cluster --- adenosine receptors --- AR ligands --- aggregation --- promiscuous mechanism --- human ecto-5?-nucleotidase --- virtual screening --- enzymatic assays --- turbidimetry --- dynamic light scattering --- docking --- solvent effect --- binding affinity --- scoring function --- molecular dynamics --- target-focused pharmacophore modeling --- density-based clustering --- structure-based drug design --- AutoGrid --- grid maps --- probe energies --- method development --- steered molecular dynamics --- all-atom molecular dynamics simulation --- resultant dipole moment --- mechanical stability --- protein-peptide interactions --- molecular dynamics --- proteins --- molecular recognition --- protein protein interactions --- artificial intelligence --- deep learning --- neural networks --- property prediction --- quantitative structure-activity relationship (QSAR) --- quantitative structure-property prediction (QSPR) --- de novo design --- adenosine receptor --- metadynamics --- extracellular loops --- allosterism --- molecular dynamics --- cosolvent molecular dynamics --- drug design --- fragment screening --- docking

Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation

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ISBN: 9783039212651 / 9783039212668 Year: Pages: 356 DOI: 10.3390/books978-3-03921-266-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-08-28 11:21:27
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Transcriptional regulation is a critical biological process involved in the response of a cell, a tissue or an organism to a variety of intra- and extra-cellular signals. Besides, it controls the establishment and maintenance of cell identity throughout developmental and differentiation programs. This highly complex and dynamic process is orchestrated by a huge number of molecules and protein networks and occurs through multiple temporal and functional steps. Of note, many human disorders are characterized by misregulation of global transcription since most of the signaling pathways ultimately target components of transcription machinery. This book includes a selection of papers that illustrate recent advances in our understanding of transcriptional regulation and focuses on many important topics, from cis-regulatory elements to transcription factors, chromatin regulators and non-coding RNAs, other than several transcriptome studies and computational analyses.

Keywords

major depressive disorder --- glioblastoma --- differentially expressed genes --- transcriptomics --- common pathway --- mouse --- miR-25-3p --- Akt1 --- AP-2? --- promoter --- cell metabolism --- p57Kip2 --- CDKN1C --- epigenetics --- disease --- cell differentiation --- placenta --- long non-coding RNA (lncRNA) --- human --- pregnancy --- high-throughput RNA sequencing (RNA-Seq) --- transcriptome --- Rsh regulon --- Novosphingobium pentaromativorans US6-1 --- sphingomonads --- RNA-seq --- N-acyl-l-homoserine lactone --- ppGpp --- selenium --- selenocysteine --- selenoproteins --- selenocysteine insertion sequence --- nonsense-mediated decay --- G-quadruplex --- transcriptional regulation --- promoter --- CRISPR/Cas9 --- PRDM gene family --- TCGA data analysis --- somatic mutations --- transcriptome profiling --- human malignancies --- tristetraprolin (TTP) --- tumorigenesis --- posttranscriptional regulation --- adenosine and uridine-rich elements (AREs) --- circRNA-disease associations --- pathway --- heterogeneous network --- Patau Syndrome --- cytogenetics --- FOXO1 --- transcription factor --- molecular pathways --- bioinformatics --- molecular docking --- and drug design --- transcription regulation --- gene expression --- causal inference --- enhancer activity --- insect --- transcription factors --- structures and functions --- research methods --- progress and prospects --- Pax3 --- Pteria penguin (Röding, 1798) --- tyrosinase --- melanin --- RNA interference --- liquid chromatograph-tandem mass spectrometer (LC-MS/MS) --- epigenetics --- gene expression --- nutrition --- transcription --- disorders --- mechanisms --- Crassostrea gigas --- Pacific oyster --- pediveliger larvae --- bioadhesive --- transcriptome --- gene expression --- interactome --- microscopy --- fertilization --- self-incompatibility --- transcriptome --- tea --- long non-coding RNAs --- cancer --- acute leukemia --- therapeutic targets --- Adiponectin --- cancer --- Adiponectin receptors --- obesity --- inflammatory response --- inflammation --- nutritional status --- n/a

AMP-Activated Protein Kinase Signalling

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ISBN: 9783038976622 Year: Pages: 452 DOI: 10.3390/books978-3-03897-663-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-03-21 14:08:22
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Starting from a kinase of interest, AMP-activated protein kinase (AMPK) has gone far beyond an average biomolecule. Being expressed in all mammalian cell types and probably having a counterpart in every eukaryotic cell, AMPK has attracted interest in virtually all areas of biological research. Structural and biophysical insights have greatly contributed to a molecular understanding of this kinase. From good old protein biochemistry to modern approaches, such as systems biology and advanced microscopy, all disciplines have provided important information. Thus, multiple links to cellular events and subcellular localizations have been established. Moreover, the crucial involvement of AMPK in human health and disease has been evidenced. AMPK accordingly has moved from an interesting enzyme to a pharmacological target. However, despite our extensive current knowledge about AMPK, the growing community is busier than ever. This book provides a snapshot of recent and current AMPK research with an emphasis on work providing molecular insight, including but not limited to novel physiological and pathological functions, or regulatory mechanisms. Up-to-date reviews and research articles are included.

Keywords

exercise --- glucose uptake --- AMP-activated protein kinase --- TBC1D4 --- AS160 --- AMP-activated protein kinase --- developmental origins of health and disease (DOHaD) --- hypertension --- kidney disease --- nutrient-sensing signals --- oxidative stress --- renin-angiotensin system --- AMPK --- autophagy --- co-expression --- microarrays --- 3T3-L1 --- adipocyte --- differentiation --- AMPK --- tight junctions --- epithelial cells --- ZO-1 --- par complex --- MDCK --- nectin-afadin --- adherent junctions --- TAK1 --- AMPK --- phosphorylation --- AMPK kinase --- endothelial nitric-oxide synthase --- vasodilation --- phenylephrine --- vasoconstriction --- endothelial cells --- ionomycin --- AMPK --- liver --- lipid metabolism --- fatty acid oxidation --- indirect calorimetry --- atrophy --- regrowth --- sirtuin 1 (SIRT1) --- peroxisome proliferator-activated receptor gamma coactivator 1-? (PGC1?) --- heat shock protein --- fiber-type --- AMPK --- monocytes --- macrophages --- differentiation --- autophagy --- AML --- MDS --- CML --- CMML --- pregnancy --- catechol-O-methyltransferase --- 2-methoxyestradiol --- preeclampsia --- gestational diabetes mellitus --- AMPK --- IL-1? --- NLRP3 --- nutrition --- dietary fatty acids --- metabolic-inflammation --- nutrigenomics --- AMPK --- LKB1 --- autophagy --- proteasome --- hypertrophy --- atrophy --- skeletal muscle --- AICAR --- mTOR --- protein synthesis --- AMPK --- epigenetics --- chromatin remodeling --- histone modification --- DNA methylation --- medulloblastoma --- sonic hedgehog --- AMPK --- AMP-activated protein kinase (AMPK) --- spermatozoa --- motility --- mitochondria --- membranes --- signaling --- stress --- assisted reproduction techniques --- AMP-activated protein kinase --- epigenetics --- protein acetylation --- KATs --- HDACs --- acetyl-CoA --- NAD+ --- AMP-activated protein kinase --- glycogen --- exercise --- metabolism --- cellular energy sensing --- energy utilization --- liver --- skeletal muscle --- metabolic disease --- glycogen storage disease --- resveratrol --- AMPK --- hepatocyte --- liver --- steatosis --- transporter --- carrier --- pump --- membrane --- energy deficiency --- AMPK --- infection --- mycobacteria --- host defense --- energy metabolism --- AMPK --- activation loop --- AID --- ?-linker --- ?-linker --- CBS --- LKB1 --- CaMKK2 --- ?RIM --- hypothalamus --- adenosine monophosphate-activated protein kinase --- adipose tissue --- food intake --- adaptive thermogenesis --- beiging --- AMPK --- HDAC4/5 --- p70S6K --- MyHC I(?), motor endplate remodeling --- soleus muscle --- mechanical unloading --- hindlimb suspension --- AMPK --- synaptic activation --- PKA --- CREB --- soluble Adenylyl cyclase --- Immediate early genes --- transcription --- AMPK --- autophagy --- metabolism --- mTOR --- ULK --- AMP-activated protein kinase --- protein kinase B --- Akt --- insulin signalling --- A769662 --- endothelial function --- n/a

DNA Replication Stress

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ISBN: 9783039213894 / 9783039213900 Year: Pages: 368 DOI: 10.3390/books978-3-03921-390-0 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 16:10:12
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This Special Issue of International Journal of Molecular Sciences (IJMS) is dedicated to the mechanisms mediated at the molecular and cellular levels in response to adverse genomic perturbations and DNA replication stress. The relevant proteins and processes play paramount roles in nucleic acid transactions to maintain genomic stability and cellular homeostasis. A total of 18 articles are presented which encompass a broad range of highly relevant topics in genome biology. These include replication fork dynamics, DNA repair processes, DNA damage signaling and cell cycle control, cancer biology, epigenetics, cellular senescence, neurodegeneration, and aging. As Guest Editor for this IJMS Special Issue, I am very pleased to offer this collection of riveting articles centered on the theme of DNA replication stress. The blend of articles builds upon a theme that DNA damage has profound consequences for genomic stability and cellular homeostasis that affect tissue function, disease, cancer, and aging at multiple levels and through unique mechanisms. I thank the authors for their excellent contributions, which provide new insight into this fascinating and highly relevant area of genome biology.

Keywords

barley --- chromosome --- DNA replication pattern --- EdU --- mutagens --- DNA replication --- DNA damage --- DNA repair --- genome integrity --- A549 cells --- H1299 cells --- heterogeneity --- DNA damage response --- 8-chloro-adenosine --- DNA replication --- S phase --- origin firing --- TopBP1 --- ATR --- DNA fiber assay --- APE2 --- ATR-Chk1 DDR pathway --- Genome integrity --- SSB end resection --- SSB repair --- SSB signaling --- DNA replication stress --- genome stability --- ubiquitin --- replication fork restart --- translesion synthesis --- template-switching --- homologous recombination --- Fanconi Anemia --- G protein-coupled receptor (GPCR) --- aging --- DNA damage --- ?-arrestin --- G protein-coupled receptor kinase (GRK) --- interactome --- G protein-coupled receptor kinase interacting protein 2 (GIT2) --- ataxia telangiectasia mutated (ATM) --- clock proteins --- energy metabolism --- neurodegeneration --- cellular senescence --- ageing --- Alzheimer’s disease --- multiple sclerosis --- Parkinson’s disease --- lipofuscin --- SenTraGorTM (GL13) --- senolytics --- DNA replication --- DNA repair --- DNA damage response --- DNA translocation --- DNA helicase --- superfamily 2 ATPase --- replication restart --- fork reversal --- fork regression --- chromatin remodeler --- C9orf72 --- ALS --- motor neuron disease --- R loops, nucleolar stress --- neurodegeneration --- Difficult-to-Replicate Sequences --- replication stress --- non-B DNA --- Polymerase eta --- Polymerase kappa --- genome instability --- common fragile sites --- Microsatellites --- cancer --- DNA double-strand repair --- premature aging --- post-translational modification --- protein stability --- replication stress --- Werner Syndrome --- Werner Syndrome Protein --- dormant origins --- replicative stress --- replication timing --- DNA damage --- genome instability --- cancer --- Thermococcus eurythermalis --- endonuclease IV --- AP site analogue --- spacer --- DNA repair --- DNA repair --- double strand break repair --- exonuclease 1 --- EXO1 --- mismatch repair --- MMR --- NER --- nucleotide excision repair --- strand displacements --- TLS --- translesion DNA synthesis --- POL? --- mutation frequency --- mutations spectra --- SupF --- mutagenicity --- oxidative stress --- DNA damage --- DNA repair --- replication --- 8-oxoG --- epigenetic --- gene expression --- helicase --- cell cycle checkpoints --- genomic instability --- G2-arrest --- cell death --- repair of DNA damage --- adaptation --- n/a

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