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Fungal Pathogenesis in Humans: The Growing Threat

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ISBN: 9783038979005 9783038979012 Year: Pages: 232 DOI: 10.3390/books978-3-03897-901-2 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Genetics
Added to DOAB on : 2019-06-26 08:44:06
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Cancer survival rates and successful organ transplantation in patients continues to increase due to improvements in early diagnosis and treatments. Since immuno-suppressive therapies are frequently used, the mortality rate due to secondary infections has become an ever-increasing problem. Opportunistic fungal infections are probably the deadliest threat to these patients due to their difficult early diagnosis, the limited effect of antifungal drugs and the appearance of resistances. In recent years, a considerable effort has been devoted to investigating the role of many virulence traits in the pathogenic outcome of fungal infections. New virulence factors (hypoxia adaptation, CO2 sensing, pH regulation, micronutrient acquisition, secondary metabolites, immunity regulators, etc.) have been reported and their molecular mechanisms of action are being thoroughly investigated. The recent application of gene-editing technologies such as CRISPr-Cas9, has opened a whole new window to the discovery of new fungal virulence factors. Accurate fungal genotyping, Next Generation Sequencing and RNAseq approaches will undoubtedly provide new clues to interpret the plethora of molecular interactions controlling these complex systems. Unraveling their intimate regulatory details will provide insights for a more target-focused search or a rational design of more specific antifungal agents. This Special Issue is show significant discoveries, proofs of concept of new theories or relevant observations in fungal pathogenesis and its regulation.

Carbonic Anhydrases and Metabolism

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ISBN: 9783038978008 9783038978015 Year: Pages: 184 DOI: 10.3390/books978-3-03897-801-5 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-04-25 16:37:17
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Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism.

Arthropod Venom Components and Their Potential Usage

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ISBN: 9783039285402 9783039285419 Year: Pages: 404 DOI: 10.3390/books978-3-03928-541-9 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Public Health --- Medicine (General)
Added to DOAB on : 2020-04-07 23:07:09
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Thousands of arthropod species, ranging from arachnids (spiders and scorpions) to hymenopterans (ants, bees, and wasps) and myriapods (centipedes), are venomous and use their venoms for both defense and predation. These venoms are invariably harmful to humans, and some may cause serious injuries, e.g., those from scorpions, spiders, and wasps. Arthropods’ venoms are also known as rich sources of biologically active compounds and have attracted the attention of toxin researchers for years. In this century, venom component analysis has progressed considerable due to the advances in analytical techniques, in particular, mass spectrometry and next-generation deep (DNA and RNA) sequencing. As such, proteomic and peptidomic analyses using LC–MS have enabled the full analysis of venom components, revealing a variety of novel peptide and protein toxins sequences and scaffolds, potentially useful as pharmacological research tools and for the development of highly selective peptide ligands and therapeutic leads, like chlorotoxin. Due to their specificity for numerous ion-channel subtypes, including voltage- and ligand-gated ion channels, arthropod neurotoxins have been investigated to dissect and treat neurodegenerative diseases and control epileptic syndromes. This Special Issue collects information on such progress, encouraging contributions on the chemical and biological characterization of venom components, not only peptides and proteins, but also small molecules, their mechanisms of action, and the development of venom-derived peptide leads.

Keywords

ant --- venom --- mass spectrometry analysis --- pilosulin-like peptide --- phospholipases D --- metalloproteases --- Loxosceles spp. --- recombinant toxins --- hybrid immunogen --- neutralizing antibodies --- antivenoms --- LyeTxI-b --- Staphylococcus aureus --- keratitis --- AMP --- mastoparan --- Acinetobacter baumannii --- stent --- cantharidin --- blister beetle --- Berberomeloe majalis --- nematicide --- ixodicide --- antifeedant --- scorpion venom --- insecticidal peptide --- mass spectrometric analysis --- de novo sequencing --- Centruroides limpidus Karch --- proteome --- scorpion --- transcriptome --- venom toxicity --- brown spider --- venom --- Loxosceles --- toxins --- biotools --- drug targets --- novel therapeutics --- spider toxin --- directed disulfide bond formation --- Nav channel activity --- Nav1.7 --- pain target --- automated patch-clamp --- bee venom --- alternative treatment --- skin --- cutaneous disease --- mechanism --- chemotherapy --- cold allodynia --- mechanical allodynia --- melittin --- neuropathic pain --- oxaliplatin --- natural antibiotics --- piperidine heterocyclic amines --- industrial biotechnology --- LTQ Orbitrap Hybrid Mass Spectrometer --- myrmecology --- venom --- pain --- ants --- wasps --- bees --- Hymenoptera --- envenomation --- toxins --- peptides --- pharmacology --- Dinoponera quadriceps --- Formicidae --- Hymenoptera venom --- proteomics --- venom allergens --- ICK-like toxins --- melittin --- insect immune system --- apoptosis --- heart contractility --- Tenebrio molitor --- bee venom --- bioinformatics --- computational docking --- homology modelling --- ion channel structure --- protein–peptide interactions --- tertiapin --- venom peptides --- virtual screening --- small hive beetle --- solitary wasp --- venom --- antimicrobial peptide --- linear cationic ?-helical peptide --- amphipathic ?-helix structure --- channel-like pore-forming activity --- antimicrobial peptide --- venom --- arthropod --- malaria --- Chagas disease --- human African trypanosomiasis --- leishmaniasis --- toxoplasmosis --- venom peptides --- FMRF-amide --- insect neurotoxin --- protons --- pH regulation --- acid-sensing ion channels --- acid-gated currents --- chronic pain --- ICK peptide --- knottins --- NaV --- spider venom --- voltage-gated sodium channel --- n/a

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