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Decades of research have identified a role for dopamine neurotransmission in prefrontal cortical function and flexible cognition. Abnormal dopamine neurotransmission underlies many cases of cognitive dysfunction. New techniques using optogenetics have allowed for ever more precise functional segregation of areas within the prefrontal cortex, which underlie separate cognitive functions. Learning theory predictions have provided a very useful framework for interpreting the neural activity of dopamine neurons, yet even dopamine neurons present a range of responses, from salience to prediction error signaling. The functions of areas like the Lateral Habenula have been recently described, and its role, presumed to be substantial, is largely unknown. Many other neural systems interact with the dopamine system, like cortical GABAergic interneurons, making it critical to understand those systems and their interactions with dopamine in order to fully appreciate dopamine's role in flexible behavior. Advances in human clinical research, like exome sequencing, are driving experimental hypotheses which will lead to fruitful new research directions, but how do (or should?) these clinical findings inform basic research? Following new information from these techniques, we may begin to develop a fresh understanding of human disease states which will inform novel treatment possibilities. However, we need an operational framework with which to interpret these new findings. Therefore, the purpose of this Research Topic is to integrate what we know of dopamine, the prefrontal cortex and flexible behavior into a clear framework, which will illuminate clear, testable directions for future research.

behavioral flexibility --- Dopamine --- medial prefrontal cortex (mPFC) --- Attentional set-shifting --- basal forebrain --- anterior cingulate cortex (ACC) --- endocannabinoid system --- lateral habenula (LHb) --- Locus coeruleus (LC) --- motivational salience

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This Book of Toxins comprises 11 original contributions and one review. New findings regarding presence of mycotoxins in aromatic and medicinal plants, mango and orange juice, juices, pulps, jams, and beer, from Morocco, Pakistan, and Portugal are reported. In these studies, innovative techniques to study their presence has been developed, including liquid chromatography coupled with time-of-flight mass spectrometry to analyse mycotoxins and conjugated mycotoxins. Novel strategies to detect mycotoxin presence and comparisons the characteristics of a rapid quantitative analysis of different mycotoxins (deoxynivalenol, ochratoxin A, patulin, sterigmatocystin, and zearalenone) are also presented using acetyl- and butyrylcholinesterases and photobacterial strains of luminescent cells. Additionally, toxicological effects of zearalenone metabolites and beauvericin on SH-SY5Y neuronal cells are presented. One important point in the control of mycotoxins is related to decontaminated strategies, and in this sense the efficacy of potentially probiotic fruit-derived Lactobacillus isolates in removing aflatoxin M1 (AFM1) is presented. Other mycotoxin decontaminated techniques included in this book are electron beam irradiation (EBI) and degradation of zearalenone and ochratoxin A using ozone. Finally, a review that summarizes the newly discovered macrocyclic trichothecenes and their bioactivities over the last decade is included.The evaluation of the presence of mycotoxins in different matrices is achieved through different analytical tools (including quantitative or qualitative determinations). Studies of mycotoxin isolation, using chromatographyc equipment coupled to spectrometry detectors (QTrap-MS/MS, MS/MS tandem, QTOF-MS/MS), are the most useful tools to control their presence. All these studies represent key steps in the establishment of the limits of detection, limits of quantification, points of identification, accuracy, reproducibility, and repeatability of different procedures. The maximum permitted or recommended levels for mycotoxins in different matrices are within a wide range (including the levels tolerated by infants and animals). In addition, decontaminated strategies, as well as control and evaluation of exposure, are demanded by authorities and food safety systems.

Medicine --- patulin --- mango --- orange --- fruit-derived products --- food safety --- regulatory limits --- chitosan --- mycotoxins --- detoxification --- LC-MS/MS --- optimization --- Destruxins --- Bombyx mori --- BmArgRS --- BmLamin-C --- RNA helicase --- binding protein --- ozone --- electron beam irradiation --- degradation --- zearalenone --- ochratoxin A --- SH-SY5Y cells --- zearalenone derivates --- beauvericin --- MTT --- qTOF–MS/MS --- beer --- immunoaffinity clean-up --- LC-FD --- human risk assessment --- Enniatin B1 --- biomonitoring --- in vivo --- metabolomics --- high resolution mass spectrometry (HRMS) --- macrocyclic trichothecenes --- bioactivities --- putative biosynthetic pathway --- macrocycle formation --- entomopathogens --- mycoinsecticides --- secondary metabolites --- insect pathogenesis --- acetamiprid accumulation --- aflatoxin M1 --- Lactobacillus --- probiotics --- binding --- bioluminescent bacteria --- immobilized cells --- cholinesterase-based analysis --- analytical characteristics --- enzymatic detoxification --- co-occurrence --- Q-TOF-LC/MS --- exposure --- Morocco --- n/a --- qTOF-MS/MS

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In recent years, there has been rapid growth in the availability of innovative, non-combustible products, including oral tobacco-derived nicotine (OTDN) products, heated tobacco products (HTPs), and electronic cigarettes (also referred to as e-vapor products; EVPs). Industry, academic, and government researchers are developing and validating analytical methods to extract, separate, identify, and quantitate a variety of analytes from these innovative tobacco products using a wide range of analytical techniques. These analytes include constituents such as nicotine, degradants and impurities, flavors, non-tobacco ingredients, HPHCs, and other currently unknown constituents. In this Special Issue, we received nine contributions that covered the latest analytical methods that have been developed and applied for the chemical characterization or exposure assessment to tobacco product constituents of innovative non-combustible products. This Special Issue is representative of the importance of analytical sciences research in characterizing innovative non-combustible products for guiding product design, determining relative product performance, ensuring consistency during the manufacturing process, informing toxicological risk assessment, and enabling regulatory reporting. The current advances in the development and applications of the analytical methods reported in this Special Issue can be used to inform the harm reduction potential of innovative non-combustible products for adult smokers.

Research & information: general --- Chemistry --- Analytical chemistry --- on!® nicotine pouches --- nicotine --- dissolution --- release profile --- validation --- product assessment --- smokeless tobacco product --- nicotine degradants --- nicotine-related impurities --- alkaloids --- nicotine degradation products --- nicotine pouches --- reduced-risk products --- constituents --- method development --- method validation --- JUUL --- aerosol --- non-targeted analysis --- chemical characterization --- ENDS --- e-cigarette --- GC–MS --- LC–HRMS --- e-liquid --- 2,4-DNPH derivatization --- formaldehyde --- “hidden formaldehyde” --- formaldehyde-containing hemiacetal/acetal adducts --- HPHC --- GC-MS --- 3-hydroxybenzo[a]pyrene --- LC–MS/MS --- urine --- human biomonitoring --- derivatization --- potentially reduced-risk products --- propylene glycol --- electronic cigarette --- biomarker of exposure --- compliance marker --- oral tobacco derived nicotine (OTDN) pouches --- snus --- nicotine release --- nicotine dissolution --- nicotine extraction --- equivalence --- modern oral nicotine products --- HPHCs --- product characterizations --- n/a --- LC-HRMS --- --- LC-MS/MS

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At present, cyanobacteria and their toxins (also known as cyanotoxins) constitute a major threat for freshwater resources worldwide. Cyanotoxin occurrence in water bodies around the globe is constantly increasing, whereas emerging, less studied or completely new variants and congeners of various chemical classes of cyanotoxins, as well as their degradation/transformation products are often detected. In addition to planctic cyanobacteria, benthic cyanobacteria, in many cases, appear to be important toxin producers, although far less studied and more difficult to manage and control. This Special Issue highlights novel research results on the structural diversity of cyanotoxins from planktic and benthic cyanobacteria, as well as on their expanding global geographical spread in freshwaters.

Research & information: general --- Environmental economics --- Meiktila Lake --- Raphidiopsis --- Microcystis --- cylindrospermopsin --- deoxycylindrospermopsin --- microcystin --- cyanobacteria --- cyanopeptides --- harmful bloom --- liquid chromatography-tandem mass spectrometry --- global natural product social networking (GNPS) --- dereplication strategy --- earthquakes --- harmful algal blooms --- sediment --- sediment cores --- co-occurrence --- toxicity --- plastics --- metals --- biocide --- anatoxin-a --- dihydroanatoxin-a --- Tychonema --- neurotoxicosis --- cyanotoxins --- macrophytes --- benthic --- tychoplanktic --- reservoir --- Maumee Bay --- Sandusky Bay --- Planktothrix --- anatoxin --- cyanotoxin detection --- harmful cyanobacterial blooms --- next-generation biomonitoring --- real-time PCR --- qPCR --- LC-MS/MS --- saxitoxin --- ESI-LC-MS/MS --- 16S rRNA phylogeny --- Azores --- eutrophication --- long term monitoring --- water quality --- microcystins --- anabaenopeptins --- microginins --- aeruginosins --- aeruginosamide --- SPE --- Lake Vegoritis --- deep-chlorophyll layers (DCLs) --- cyanobacterial toxins --- allelopathy --- bioactive metabolites --- hypoxia --- Georgian Bay --- peptide --- NRPS --- anabaenopeptin --- Synechococcus --- temperate lakes --- cyanotoxins (CTs) --- microcystins (MCs) --- volatile organic compounds (VOCs) --- taste and odor (T&O) compounds --- SPE-LC-MS/MS --- HS-SPME-GC/MS --- LC–qTRAP MS/MS --- fragmentation spectra --- structure elucidation --- cyanobacterial metabolites --- Greek freshwaters --- planktonic cyanobacteria --- blooms --- monitoring --- analysis --- mass spectrometry --- Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) --- fish tissue --- shellfish --- detection methods --- n/a --- LC-qTRAP MS/MS

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Since its early introduction by the Russian botanist Mikhail Semyonovich Tsvet, chromatography has been undoubtedly the most powerful analytical tool in analytical chemistry. Separation, qualitative analysis, and quantitative analysis can be achieved by choosing the right conditions. Thus, numerous gas chromatographic, liquid chromatographic, and supercritical fluid chromatographic methods have been developed and applied for most types of samples and most kinds of analytes. Additionally, older varieties such as paper chromatography and thin-layer chromatography were pioneer analytical techniques in many laboratories. Especially when hyphenated to spectrometric techniques, chromatography also allows the identification of separated analytes in a single run. Highly sophisticated equipment can answer all analytical problems very quickly. Chromatographers cooperate with many scientific fields and give their lights to medical doctors, veterinarians, food scientists, biologists, dentists, archaeologists, etc. In this Special Issue, analytical chemists were invited to prove that chromatography-based separation techniques are the ultimate analytical tool and their significant contribution is reflected in ten interesting articles.

Research & information: general --- Chemistry --- Analytical chemistry --- polyamine --- steroid --- breast cancer --- liquid chromatography–tandem mass spectrometry --- serum --- photoaging --- proteomics --- genomics --- Swietenia macrophylla --- UV irradiation --- keratinocytes --- epidermal layer --- cosmetics --- natural product --- LC-MS/MS --- metabolomics --- targeted analysis --- nontargeted analysis --- sample preparation --- derivatization --- validation --- biomarkers --- mycophenolate mofetil --- mycophenolic acid --- pediatric patients --- limited sampling strategy --- multiple linear regression --- therapeutic drug monitoring --- almonds --- HPLC --- authenticity --- PCA --- tocopherols --- phenolics --- method validation --- Miang --- catechins --- caffeine --- gallic acid --- walnut septum --- UAE --- SPE --- flavonoids --- functional --- HPLC-DAD --- biotin acceptor peptide (BAP) --- biotin ligase BirA --- liquid chromatography tandem mass spectrometry (LC-MS/MS) --- multiple reaction monitoring (MRM) --- protein–protein interactions (PPIs) --- proximity utilizing biotinylation (PUB) --- greener HPTLC --- paracetamol --- simultaneous determination --- microflow LC-MS --- mLC-MS/MS --- liver fibrosis --- hemopexin --- biomarker