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Ribosome inactivating proteins (RIPs) form a vast family of hundreds of toxins from plants, fungi, algae and bacteria. RIP activities have also been detected in animal tissues. They target a single adenine of a ribosomal RNA, thereby blocking protein synthesis and leading intoxicated cells to apoptosis. The role of plant RIPs may be related to plant defense against predators and viruses, plant senescence or bacterial pathogenesis. Most RIPs are no threat to human or animal health. However, several bacterial RIPs are major virulence factors involved in severe epidemic diseases such as dysentery or the hemolytic uremic syndrome that may occur in patients suffering from Shiga toxin-producing entero-hemorrhagic Escherichia coli infection. Several plant RIPs such as ricin toxin, abrin or sarcin have been, or may be involved in accidental or criminal poisonings, political intimidation or bio-suicides. Health crisis, biosafety and biosecurity issues became a major concern and many efforts are made to develop treatments. Finally, RIPs can be engineered into immunotoxins to destroy cancer cells or cells chronically infected by viruses. This book presents the most recent data on all aspects of RIPs including function, diversity and evolution, mechanism, pathophysiology, medical countermeasures and engineering into anticancer drugs.
toxin --- Shiga toxin --- ricin --- Ribosome inactivating protein
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The nucleolus is a prominent nuclear domain that is common to eukaryotes. Since the nucleolus was first described in the 1830s, its identity had remained a mystery for longer than 100 years. Major advances in understanding of the nucleolus were achieved through electron microscopic and biochemical studies in the 1960s to 1970s followed by molecular biological studies. These studies finally established the view of the nucleolus that it is a large aggregate of RNA-protein complexes associated with the rRNA gene region of chromosome DNA, serving mainly as a site of ribosome biogenesis, where pre-rRNA transcription, pre-rRNA processing, and ribosome assembly occur. This function of the nucleolus appears to indicate that the nucleolus plays a constitutive and essential role in fundamental cellular activities by producing ribosomes. Recent research has shown, however, that the nucleolus is more dynamic and can have more specific and wider functions. In plants, nucleolar functions have been implicated in developmental regulations and environmental responses by accumulating pieces of evidence obtained mostly from genetic studies of nucleolar factor-related mutants. Comprehensive analysis of nucleolar proteins and molecular cytological characterization of sub-nucleolar and peri-nucelolar bodies have also provided new insights into behaviors and functions of the plant nucleolus.
In this Research Topic, we would like to collect physiological and molecular links between the nucleolus to plant growth and development, shed light on novel aspects of nucleolar functions beyond its classical view, and stimulate research activities focusing on the nucleolus across various fields of plant science, including molecular biology, cell biology, genetics, developmental biology, physiology, and evolutionary biology.environmental response --- development --- plant --- nucleolus --- growth --- ribosome biogenesis
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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact
antibiotic resistance --- antibiotic inactivation --- multi-drug-resistance --- cell wall alteration --- efflux pumps --- ribosome --- bacteria
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This Open Access volume provides comprehensive reviews and describes the latest techniques to study eukaryotic ribosome biogenesis. For more than 50 years ribosomes are a major research topic. Our knowledge about ribosome biogenesis and function such as transcription, mRNA modification, and translation was the sine qua non for developing the powerful RNA-based vaccines against RNA-viruses causing the world-threatening Covid-19 pandemia. The chapters in this book are organized into six parts. Part One discusses a comparative survey about the unity and diversity of ribosome biogenesis in pro- and eukaryotic cells. Part Two deals with the genomic organization of eukaryotic rDNA and the role of RNA polymerase I in ribosomal RNA transcription. Part Three explores in vitro methods to study RNA polymerase I structure and its function, and Part Four analyzes the nucleo-cytoplasmic transport of assembled ribosomes and RNP complexes. Part Five covers modifications that increase the complexity of rRNAs, and Part Six provides readers with a review of eukaryotic translation and - for the first time - describes a new method to analyze translation in vitro. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, Ribosome Biogenesis: Methods and Protocols is a valuable resource for scientists and researchers interested in learning more about the increasing importance of in vitro RNA-technologies.
Medical genetics. --- Medical Genetics. --- Clinical genetics --- Diseases --- Heredity of disease --- Human genetics --- Medical sciences --- Pathology --- Genetic disorders --- Genetic aspects --- cryo-electron microscopy --- ribosome biogenesis --- subtunit protein composition --- eukaryotes --- maturation
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The intent of this volume of Current Topics in Microbiology and Immunology was to bring together a collection of in-depth and cutting edge reviews that highlight our current understanding of the biology of ricin and Shiga toxin (Stx), with the long term goal of advancing the development of countermeasures against these toxic agents. In May of 2011, Western Europe experienced a severe outbreak of Stx-producing E. coli (STEC) that culminated in more than 3200 cases and 39 deaths. While Stx is not the only virulence factor associated with STEC, it is certainly the primary determinant associated with the onset of hemolytic uremic syndrome (HUS). At the present time, there are no clinically approved measures to neutralize Stx in individuals suffering from STEC infection. Nor are there any preventatives or therapeutics for ricin toxin. Although incidents of ricin exposure are largely unheard of, federal agencies and public health officials consider it a significant threat. It is well documented that domestic and international terrorist groups have stockpiled, and in some cases weaponized ricin with the intent of releasing it into the public sphere and causing panic, illness and/or death on a local, regional, or possibly national scale. As the title of this volume indicates, the chapters, written by leading experts in the field, are organized so as to cover all aspects of ricin and Stx, including pathogenesis, immunity, vaccines and therapeutics. This outstanding collection of reviews will serve as an important and readily accessible resource for the research community in the coming years. .
Antigens and antibodies. --- Chemical agents (Munitions) -- Toxicology. --- Ricin. --- Toxins. --- Verocytotoxins. --- Ricin --- Verocytotoxins --- Chemical agents (Munitions) --- Immunoglobulins --- Ribosome Inactivating Proteins, Type 2 --- Enterotoxins --- Plant Lectins --- Bacterial Toxins --- Albumins --- Ribosome Inactivating Proteins --- Proteins --- Toxins, Biological --- Lectins --- Biological Factors --- N-Glycosyl Hydrolases --- Amino Acids, Peptides, and Proteins --- Plant Proteins --- Glycoside Hydrolases --- Chemicals and Drugs --- Hydrolases --- Enzymes --- Enzymes and Coenzymes --- Shiga Toxins --- Biology --- Health & Biological Sciences --- Microbiology & Immunology --- Pharmacy, Therapeutics, & Pharmacology --- Toxicology --- Immunotherapy. --- Vaccines. --- Therapeutic immunology --- Natural toxicants --- Toxicants, Natural --- Toxins and antitoxins --- Castor bean lectin --- Ricinus lectin --- Medicine. --- Pharmacology. --- Biomedicine. --- Pharmacology/Toxicology. --- Drug effects --- Medical pharmacology --- Medical sciences --- Chemicals --- Chemotherapy --- Drugs --- Pharmacy --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Pathology --- Physicians --- Physiological effect --- Biologicals --- Clinical immunology --- Therapeutics --- Antigens --- Metabolites --- Poisons --- Antitoxins --- Detoxification (Health) --- Plant lectins --- Plant toxins --- Toxalbumins --- Toxicology. --- Medicine --- Pharmacology --- Poisoning
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Protein import into the endoplasmic reticulum (ER) is the first step in the biogenesis of approximately 10,000 different soluble and membrane proteins of human cells, which amounts to about 30% of the proteome. Most of these proteins fulfill their functions either in the membrane or lumen of the ER plus the nuclear envelope, in one of the organelles of the pathways for endo- and exocytosis (ERGIC, Golgi apparatus, endosome, lysosome, and trafficking vesicles), or at the cell surface as plasma membrane or secreted proteins. An increasing number of membrane proteins destined to lipid droplets, peroxisomes or mitochondria are first targeted to and inserted into the ER membrane prior to their integration into budding lipid droplets or peroxisomes or prior to their delivery to mitochondria via the ER-SURF pathway. ER protein import involves two stages, ER targeting, which guarantees membrane specificity, and the insertion of nascent membrane proteins into or translocation of soluble precursor polypeptides across the ER membrane. In most cases, both processes depend on amino-terminal signal peptides or transmembrane helices, which serve as signal peptide equivalents. However, the targeting reaction can also involve the ER targeting of specific mRNAs or ribosome–nascent chain complexes. Both processes may occur co- or post-translationally and are facilitated by various sophisticated machineries, which reside in the cytosol and the ER membrane, respectively. Except for resident ER and mitochondrial membrane proteins, the mature proteins are delivered to their functional locations by vesicular transport.
chaperones --- contact sites --- endoplasmic reticulum --- ER-SURF --- membrane extraction --- mitochondria --- protein targeting --- bimolecular luminescence complementation --- competition --- split luciferase --- membrane proteins --- protein–protein interactions --- Sec61 complex --- Sec63 --- synthetic peptide complementation --- TRAP complex --- ER protein translocase --- signal peptide --- protein translocation --- nascent peptide chain --- membrane insertion --- molecular modelling --- molecular dynamics simulations --- molecular docking --- signal peptidase --- ER translocon --- signal recognition particle dependent protein targeting --- Sec61 dependent translocation --- co-translational translocation --- inhibitor --- high throughput screening --- Sec61 --- Sec62 --- folding --- insertion --- membrane protein --- translocon --- ribosome --- transmembrane segment --- lipid droplets --- peroxisomes --- PEX3 --- membrane protein insertion --- label-free quantitative mass spectrometry --- differential protein abundance analysis --- Zellweger syndrome --- GET --- protein transport --- SND --- SRP --- EMC --- positive-inside rule --- hydrophobicity --- transmembrane helix --- signal recognition particle --- nascent polypeptide-associated complex --- fidelity --- cyclotriazadisulfonamide --- ER quality control --- DNAJC3 --- preprotein --- Sec61 translocon --- ribosome stalling --- signal sequence --- Sec61 translocase --- NAC --- n/a --- protein-protein interactions
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Many plants produce enzymes collectively known as ribosome-inactivating proteins (RIPs). RIPs catalyze the removal of an adenine residue from a conserved loop in the large ribosomal RNA. The adenine residue removed by this depurination is crucial for the binding of elongation factors. Ribosomes modified in this way are no longer able to carry out protein synthesis. Most RIPs exist as single polypeptides (Type 1 RIPs) which are largely non-toxic to mammalian cells because they are unable to enter them and thus cannot reach their ribosomal substrate. In some instances, however, the RIP forms part of a heterodimer where its partner polypeptide is a lectin (Type 2 RIPs). These heterodimeric RIPs are able to bind to and enter mammalian cells. Their ability to reach and modify ribosomes in target cells means these proteins are some of the most potently cytotoxic poisons found in nature, and are widely assumed to play a protective role as part of the host plant’s defenses. RIPs are able to further damage target cells by inducing apoptosis. In addition, certain plants produce lectins lacking an RIP component but which are also cytotoxic. This book focuses on the structure/function and some potential applications of these toxic plant proteins.
Plant proteins. --- Polypeptides. --- Plant proteins --- Polypeptides --- Plant Proteins --- Lectins --- N-Glycosyl Hydrolases --- Proteins --- Glycoside Hydrolases --- Plant Lectins --- Ribosome Inactivating Proteins --- Amino Acids, Peptides, and Proteins --- Hydrolases --- Enzymes --- Chemicals and Drugs --- Enzymes and Coenzymes --- Botany --- Earth & Environmental Sciences --- Plant Physiology --- Life sciences. --- Plant biochemistry. --- Cell biology. --- Plant science. --- Botany. --- Plant physiology. --- Life Sciences. --- Plant Biochemistry. --- Cell Biology. --- Plant Physiology. --- Plant Sciences. --- Biopolymers --- Peptides --- Plant polymers --- Biochemistry. --- Cytology. --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Biology --- Chemistry --- Medical sciences --- Botanical science --- Phytobiology --- Phytography --- Phytology --- Plant biology --- Plant science --- Natural history --- Plants --- Physiology --- Cell biology --- Cellular biology --- Cells --- Cytologists --- Composition --- Floristic botany --- Phytochemistry --- Plant biochemistry --- Plant chemistry --- Biochemistry --- Phytochemicals --- Plant biochemical genetics
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This Special Issue examines state-of-the-art in-cell NMR spectroscopy as it relates to biological systems of increasing complexity. The compendia of research and recent innovations from prominent laboratories in the field of solid state and solution in-cell NMR spectroscopy, metabolomics and technology development are presented. The work establishes in-cell NMR spectroscopy as the premier method for determining the structures and interaction capabilities of biological molecules at high resolution within the delicately intricate interior of living cells, and the means of utilizing cells as living laboratories to directly assess the effects of exogenous and endogenous stimuli on cell physiology.]
protein NMR --- time-resolved NMR --- Ribosome --- structural calculation 4 --- crystalline and amorphous starch --- in-cell NMR --- protein dynamics --- DNP --- protein modification --- Tau --- spectrum reconstruction 3 --- mRNA --- Thioredoxin --- protein structure --- protein interactions --- drug discovery --- protein structure determination 1 --- review --- enzyme activity --- MARK2 phosphorylation --- post-translational modifications --- Dihydrofolate reductase --- mammalian cells --- target engagement --- non-uniform sampling 2 --- paramagnetic effects --- protein structure-function --- cross-correlated relaxation --- structure function --- rRNA --- 2D INADEQUATE --- lipid membrane --- Thymidylate synthase --- whole cell NMR --- enzyme kinetics --- magic-angle spinning --- live cell --- solid-state NMR --- Adenylate kinase --- DNA --- in-situ NMR --- antimicrobial peptide --- NMR spectroscopy --- intrinsically disordered proteins
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Apomixis is the consequence of a concerted mechanism that harnesses the sexual machinery and coordinates developmental steps in the ovule to produce an asexual (clonal) seed. Altered sexual developments involve widely characterized functional and anatomical changes in meiosis, gametogenesis, and embryo and endosperm formation. The ovules of apomictic plants skip meiosis and form unreduced female gametophytes whose egg cells develop into a parthenogenetic embryo, and the central cells may or may not fuse to a sperm to develop the seed endosperm. Thus, functional apomixis involves at least three components, apomeiosis, parthenogenesis, and endosperm development, modified from sexual reproduction that must be coordinated at the molecular level to progress through the developmental steps and form a clonal seed. Despite recent progress uncovering specific genes related to apomixis-like phenotypes and the formation of clonal seeds, the molecular basis and regulatorynetwork of apomixis is still unknown. This is a central problem underlying the current limitations of apomixis breeding. This book collates twelve publications addressing different topics around the molecular basis of apomixis, illustrating recent discoveries and advances toward understanding the genetic regulation of the trait, discussing the possible origins of apomixis and the remaining challenges for its commercial deployment in plants.
apomixis --- evolution --- germline --- gene regulation --- sporogenesis --- plant reproduction --- ribosome --- RNA helicase --- sexual development --- stress response --- apomeiosis --- clonal seeds --- endosperm --- heterosis capture --- molecular breeding --- parthenogenesis --- differentially expressed genes --- hybridization --- microarrays --- polyploidy --- Ranunculus --- sexuality --- character segregation --- crop biotechnology --- heterosis --- meiosis --- recombination --- agamospermy --- basal angiosperms (ANA-grade) --- sporocyteless --- polycomb-group proteins --- reproductive systems --- apomixis evolution --- APOSTART --- Poa pratensis --- diplospory --- autonomous endosperm --- genetics --- Taraxacum --- dandelion --- weeping lovegrass --- drought stress --- RNA-seq --- plant breeding --- plant development --- Hieracium piloselloides --- CRISPR/Cas9 --- PHYTOENE DESATURASE (PDS) --- amplicon sequencing --- genome editing --- tissue culture --- haploid progeny --- dicotyledon --- PsASGR-BBML --- pseudogamy --- 5-azacytidine --- abscisic acid --- apospory --- expression profiling --- fluridone --- metabolic homeostasis --- oxidative stress --- sucrose non-fermenting-related protein kinase --- n/a
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Targeted therapy has developed significantly in the last one and half decades, prescribing specific medications for treatment of particular diseases, such as cancer, diabetes, and heart disease. One of the most exciting recent developments in targeted therapies was the isolation of disease-specific molecules from natural resources, such as animal venoms and plant metabolites/toxins, for use as templates for new drug motif designs. In addition, the study of venom proteins/peptides and toxins naturally targeted mammalian receptors and demonstrated high specificity and selectivity towards defined ion channels of cell membranes. Research has also focsed intensely on receptors. The focus of this Special Issue of Toxins addressed the most recent advances using animal venoms, such as frog secretions, bee/ant venoms and plant/fungi toxins, as medicinal therapy. Recent advances in venom/toxin/immunotoxins for targeted cancer therapy and immunotherapy, along with using novel disease-specific venom-based protein/peptide/toxin and currently available FDA-approved drugs for combinationtreatments will be discussed. Finally, we included an overview of select promising toad/snake venom-based peptides/toxins potentially able to address the forthcoming challenges in this field. Both research and review articles proposing novelties or overviews, respectively, were published in this Special Issue after rigorous evaluation and revision by expert peer reviewers.
cane toad --- n/a --- B cell non-Hodgkin lymphoma --- Malaysian cobras --- complement system --- decay accelerating factor --- neuroblastoma --- atopic dermatitis --- complement dependent cytotoxicity --- antioxidant enzymes --- bacterial adhesion --- cancer therapy --- N. kaouthia --- anuran skin secretion --- frog --- Apis mellifera syriaca --- solid phase extraction --- bee venom phospholipase A2 (bvPLA2) --- disintegrin --- toad toxins --- immunotoxins --- ribosome-inactivating proteins --- antimicrobial peptide (AMP) --- drug design --- Moxetumomab pasudotox --- snake venom --- antiviral activity --- in vitro effects --- bombesin-related peptide --- oxidative stress biomarkers --- half-life --- blood vessel formation --- target therapy --- 2 --- MYCN --- indolealkylamines --- Huachansu --- membrane attack complex --- bouganin --- bee venom --- SEM --- anticancer activity --- antimicrobial peptide --- house dust mite extract (DFE) --- mannose receptor --- O. hannah --- bicarinalin --- gastric cells --- melittin --- LC-ESI-MS --- dermaseptin --- smooth muscle --- apoptosis --- anticancer --- N. sumatrana --- Helicobacter pylori --- inflammation --- immunotherapy --- atopic dermatitis (AD) --- immunotoxin --- mantle cell lymphoma --- clearance --- mass spectrometry --- Bougainvillea --- rRNA N-glycosylase activity --- fungal toxin --- skin inflammation --- targeted therapy --- 4-dinitrochlorobenzene (DNCB) --- Bee venom --- VEGF --- Chansu --- bufadienolides --- obsessive–compulsive disorder (OCD) --- BLF1 --- antimicrobial activity --- orellanine --- VB6-845 --- acute lymphoblastic leukemia --- ribosome-inactivating protein --- CD206 --- molecular cloning --- cancer --- CD22 --- eIF4A --- obsessive-compulsive disorder (OCD)
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