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Head of Institute: Prof. Ido Braslavsky

Administrative manager: Rakefet Kalev

Office Address:
Institute of Biochemistry, Food Science and Nutrition,
Robert H. Smith Faculty of Agriculture, Food and Environment,
The Hebrew University of Jerusalem, 
Herzl 229, Rehovot 7610001, ISRAEL

Tel: +972 - (0)8-9489385
Fax: +972 - (0)8-9363208
Email Address: rakefetk@savion.huji.ac.il

Publications

2019
Arafeh, R. ; Di Pizio, A. ; Elkahloun, A. G. ; Dym, O. ; Niv, M. Y. ; Samuels, Y. . Rasa2 And Nf1; Two-Negative Regulators Of Ras With Complementary Functions In Melanoma. Oncogene 2019, 38, 2432 - 2434. Publisher's Version
Qutob, N. ; Masuho, I. ; Alon, M. ; Emmanuel, R. ; Cohen, I. ; Di Pizio, A. ; Madore, J. ; Elkahloun, A. ; Ziv, T. ; Levy, R. ; et al. Author Correction: Rgs7 Is Recurrently Mutated In Melanoma And Promotes Migration And Invasion Of Human Cancer Cells. Scientific Reports 2019, 9, 4523. Publisher's VersionAbstract
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Qin, C. ; Qin, Z. ; Zhao, D. ; Pan, Y. ; Zhuang, L. ; Wan, H. ; Di Pizio, A. ; Malach, E. ; Niv, M. Y. ; Huang, L. ; et al. A Bioinspired In Vitro Bioelectronic Tongue With Human T2R38 Receptor For High-Specificity Detection Of N-C=S-Containing Compounds. Talanta 2019, 199, 131 - 139. Publisher's VersionAbstract
Detection and identification of bitter compounds draw great attention in pharmaceutical and food industry. Several well-known agonists of specific bitter taste receptors have been found to exhibit anti-cancer effects. For example, N-C=S-containing compounds, such as allyl-isothiocyanates, have shown cancer chemo-preventive effects. It is worth noting that human T2R38 receptor is specific for compounds containing N-C=S moiety. Here, a bioinspired cell-based bioelctronic tongue (BioET) is developed for the high-specificity isothiocyanate-induced bitter detection, utilizing human Caco-2 cells as a primary sensing element and interdigitated impedance sensor as a secondary transducer. As an intestinal carcinoma cell line, Caco-2 endogenously expresses human bitter receptor T2R38, and the activation of T2R38 induces the changes of cellular morphology which can be detected by electric cell-substrate impedance sensing (ECIS). After configuration and optimization of parameters including timing of compound administration and cell density, quantitative bitter evaluation models were built for two well-known bitter compounds, phenylthiocarbamide (PTC) and propylthiouracil (PROP). The bitter specific detection of this BioET is inhibited by probenecid and U-73122, and is not elicited by other taste modalities or bitter ligands that do not activate T2R38. Moreover, by combining different computational tools, we designed a ligand-based virtual screening (LBVS) protocol to select ligands that are likely to activate T2R38 receptor. Three computationally predicted agonists of T2R38 were selected using the LBVS protocol, and the BioET presented response to the predicted agonists, validating the capability of the LBVS protocol. This study suggests this unique cell-based BioET paves a general and promising way to specifically detect N-C=S-containing compounds that can be used for pharmaceutical study and drug development.
2018
Bahia, M. S. ; Nissim, I. ; Niv, M. Y. . Bitterness Prediction In-Silico: A Step Towards Better Drugs. International Journal of Pharmaceutics 2018, 536, 526 - 529. Publisher's VersionAbstract
Bitter taste is innately aversive and thought to protect against consuming poisons. Bitter taste receptors (Tas2Rs) are G-protein coupled receptors, expressed both orally and extra-orally and proposed as novel targets for several indications, including asthma. Many clinical drugs elicit bitter taste, suggesting the possibility of drugs re-purposing. On the other hand, the bitter taste of medicine presents a major compliance problem for pediatric drugs. Thus, efficient tools for predicting, measuring and masking bitterness of active pharmaceutical ingredients (APIs) are required by the pharmaceutical industry. Here we highlight the BitterDB database of bitter compounds and survey the main computational approaches to prediction of bitter taste based on compound's chemical structure. Current in silico bitterness prediction methods provide encouraging results, can be constantly improved using growing experimental data, and present a reliable and efficient addition to the APIs development toolbox.
Xue, A. Y. ; Di Pizio, A. ; Levit, A. ; Yarnitzky, T. ; Penn, O. ; Pupko, T. ; Niv, M. Y. . Corrigendum: Independent Evolution Of Strychnine Recognition By Bitter Taste Receptor Subtypes. Frontiers in Molecular Biosciences 2018, 5, 84. Publisher's Version
Di Pizio, A. ; Shy, N. ; Behrens, M. ; Meyerhof, W. ; Niv, M. Y. . Molecular Features Underlying Selectivity In Chicken Bitter Taste Receptors. Frontiers in Molecular Biosciences 2018, 5, 6. Publisher's VersionAbstract
Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors (Gallus gallus taste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles towards the three receptors, to shed light on the molecular recognition complexity in bitter taste. Using homology modeling and induced-fit docking simulations, we investigated the binding modes of ggTas2r agonists. Interestingly, promiscuous compounds are predicted to establish polar interactions with position 6.51 and hydrophobic interactions with positions 3.32 and 5.42 in all ggTas2rs; whereas certain residues are responsible for receptor selectivity. Lys3.29 and Asn3.36 are suggested as ggTas2r1-specificity-conferring residues; Gln6.55 as ggTas2r2-specificity-conferring residue; Ser5.38 and Gln7.42 as ggTas2r7-specificity conferring residues. The selectivity profile of quinine analogs, quinidine, epiquinidine and ethylhydrocupreine, was then characterized by combining calcium-imaging experiments and in-silico approaches. ggTas2r models were used to virtually screen BitterDB compounds.  50% of compounds known to be bitter to human are likely to be bitter to chicken, with 25%, 20%, 37% predicted to be ggTas2r1, ggTas2r2, ggTas2r7 agonists, respectively. Predicted ggTas2rs agonists can be tested with in-vitro and in-vivo experiments, contributing to our understanding of bitter taste in chicken and, consequently, to the improvement of chicken feed.
Xue, A. Y. ; Di Pizio, A. ; Levit, A. ; Yarnitzky, T. ; Penn, O. ; Pupko, T. ; Niv, M. Y. . Independent Evolution Of Strychnine Recognition By Bitter Taste Receptor Subtypes. Frontiers in Molecular Biosciences 2018, 5, 9. Publisher's VersionAbstract
The 25 human bitter taste receptors (hT2Rs) recognize thousands of structurally and chemically diverse bitter substances. The binding modes of human bitter taste receptors hT2R10 and hT2R46, which are responsible for strychnine recognition, were previously established using site-directed mutagenesis, functional assays and molecular modeling. Here we construct a phylogenetic tree and reconstruct ancestral sequences of the T2R10 and T2R46 clades. We next analyze the binding sites in view of experimental data to predict their ability to recognize strychnine. This analysis suggests that the common ancestor of hT2R10 and hT2R46 is unlikely to bind strychnine in the same mode as either of its two descendants. Estimation of relative divergence times shows that hT2R10 evolved earlier than hT2R46. Strychnine recognition was likely acquired first by the earliest common ancestor of the T2R10 clade before the separation of primates from other mammals, and was highly conserved within the clade. It was probably independently acquired by the common ancestor of T2R43-47 before the homo-ape speciation, lost in most T2Rs within this clade, but enhanced in the hT2R46 after humans diverged from the rest of primates. Our findings suggest hypothetical strychnine T2R receptors in several species, and serve as an experimental guide for further study. Improved understanding of how bitter taste receptors acquire the ability to be activated by particular ligands is valuable for the development of sensors for bitterness and for potential toxicity.
Ben Abu, N. ; Harries, D. ; Voet, H. ; Niv, M. Y. . The Taste Of Kcl &Ndash; What A Difference A Sugar Makes. Food Chemistry 2018, 255, 165 - 173. Publisher's VersionAbstract
Dramatic increase in NaCl consumption lead to sodium intake beyond health guidelines. KCl substitution helps reduce sodium intake but results in a bitter-metallic off-taste. Two disaccharides, trehalose and sucrose, were tested in order to untangle the chemical (increase in effective concentration of KCl due to sugar addition) from the sensory effects. The bitter-metallic taste of KCl was reduced by these sugars, while saltiness was enhanced or unaltered. The perceived sweetness of sugar, regardless of its type and concentration, was an important factor in KCl taste modulation. Though KCl was previously shown to increase the chemical activity of trehalose but not of sucrose, we found that it suppressed the perceived sweetness of both sugars. Therefore, sensory integration was the dominant factor in the tested KCl-sugar combinations.
Nowak, S. ; Di Pizio, A. ; Levit, A. ; Niv, M. Y. ; Meyerhof, W. ; Behrens, M. . Reengineering The Ligand Sensitivity Of The Broadly Tuned Human Bitter Taste Receptor Tas2R14. Biochimica et Biophysica Acta (BBA) - General Subjects 2018, 1862, 2162 - 2173. Publisher's VersionAbstract
BackgroundIn humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute disproportionally high to the perception of bitterness. Perhaps the most broadly tuned receptor is the TAS2R14, which may represent, because of its prominent expression in extraoral tissues, a receptor of particular importance for the physiological actions of bitter compounds beyond taste. Methods To investigate how the architecture and composition of the TAS2R14 binding pocket enables specific interactions with a complex array of chemically diverse bitter agonists, we carried out homology modeling and ligand docking experiments, subjected the receptor to point-mutagenesis of binding site residues and performed functional calcium mobilization assays. Results In total, 40 point-mutated receptor constructs were generated to investigate the contribution of 19 positions presumably located in the receptor's binding pocket to activation by 7 different TAS2R14 agonists. All investigated positions exhibited moderate to pronounced agonist selectivity. Conclusions Since numerous modifications of the TAS2R14 binding pocket resulted in improved responses to individual agonists, we conclude that this bitter taste receptor might represent a suitable template for the engineering of the agonist profile of a chemoreceptive receptor. General significance The detailed structure-function analysis of the highly promiscuous and widely expressed TAS2R14 suggests that this receptor must be considered as potentially frequent target for known and novel drugs including undesired off-effects.
Dagan-Wiener, A. ; Di Pizio, A. ; Nissim, I. ; Bahia, M. S. ; Dubovski, N. ; Margulis, E. ; Niv, M. Y. . Bitterdb: Taste Ligands And Receptors Database In 2019. Nucleic Acids Researchnar 2018, 47, D1179 - D1185. Publisher's VersionAbstract
BitterDB (http://bitterdb.agri.huji.ac.il) was introduced in 2012 as a central resource for information on bitter-tasting molecules and their receptors. The information in BitterDB is frequently used for choosing suitable ligands for experimental studies, for developing bitterness predictors, for analysis of receptors promiscuity and more. Here, we describe a major upgrade of the database, including significant increase in content as well as new features. BitterDB now holds over 1000 bitter molecules, up from the initial 550. When available, quantitative sensory data on bitterness intensity as well as toxicity information were added. For 270 molecules, at least one associated bitter taste receptor (T2R) is reported. The overall number of ligand–T2R associations is now close to 800. BitterDB was extended to several species: in addition to human, it now holds information on mouse, cat and chicken T2Rs, and the compounds that activate them. BitterDB now provides a unique platform for structure-based studies with high-quality homology models, known ligands, and for the human receptors also data from mutagenesis experiments, information on frequently occurring single nucleotide polymorphisms and links to expression levels in different tissues.
Di Pizio, A. ; Shy, N. ; Behrens, M. ; Meyerhof, W. ; Niv, M. Y. . Molecular Features Underlying Selectivity In Chicken Bitter Taste Receptors. Front Mol Biosci 2018, 5, 6.Abstract
Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors ( taste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles toward the three receptors, to shed light on the molecular recognition complexity in bitter taste. Using homology modeling and induced-fit docking simulations, we investigated the binding modes of ggTas2r agonists. Interestingly, promiscuous compounds are predicted to establish polar interactions with position 6.51 and hydrophobic interactions with positions 3.32 and 5.42 in all ggTas2rs; whereas certain residues are responsible for receptor selectivity. Lys and Asn are suggested as ggTas2r1-specificity-conferring residues; Gln as ggTas2r2-specificity-conferring residue; Ser and Gln as ggTas2r7-specificity conferring residues. The selectivity profile of quinine analogs, quinidine, epiquinidine and ethylhydrocupreine, was then characterized by combining calcium-imaging experiments and approaches. ggTas2r models were used to virtually screen BitterDB compounds. ~50% of compounds known to be bitter to human are likely to be bitter to chicken, with 25, 20, 37% predicted to be ggTas2r1, ggTas2r2, ggTas2r7 agonists, respectively. Predicted ggTas2rs agonists can be tested with and experiments, contributing to our understanding of bitter taste in chicken and, consequently, to the improvement of chicken feed.
Qutob, N. ; Masuho, I. ; Alon, M. ; Emmanuel, R. ; Cohen, I. ; Di Pizio, A. ; Madore, J. ; Elkahloun, A. ; Ziv, T. ; Levy, R. ; et al. Rgs7 Is Recurrently Mutated In Melanoma And Promotes Migration And Invasion Of Human Cancer Cells. Scientific Reports 2018, 8, 653. Publisher's VersionAbstract
Analysis of 501 melanoma exomes revealed RGS7, which encodes a GTPase-accelerating protein (GAP), to be a tumor-suppressor gene. RGS7 was mutated in 11% of melanomas and was found to harbor three recurrent mutations (p.R44C, p.E383K and p.R416Q). Structural modeling of the most common recurrent mutation of the three (p.R44C) predicted that it destabilizes the protein due to the loss of an H-bond and salt bridge network between the mutated position and the serine and aspartic acid residues at positions 58 as 61, respectively. We experimentally confirmed this prediction showing that the p.R44C mutant protein is indeed destabilized. We further show RGS7 p.R44C has weaker catalytic activity for its substrate Gαo, thus providing a dual mechanism for its loss of function. Both of these effects are expected to contribute to loss of function of RGS7 resulting in increased anchorage-independent growth, migration and invasion of melanoma cells. By mutating position 56 in the R44C mutant from valine to cysteine, thereby enabling the formation of a disulfide bridge between the two mutated positions, we slightly increased the catalytic activity and reinstated protein stability, leading to the rescue of RGS7′s function as a tumor suppressor. Our findings identify RGS7 as a novel melanoma driver and point to the clinical relevance of using strategies to stabilize the protein and, thereby, restore its function.
2017
Oren, T. ; Nimri, L. ; Yehuda-Shnaidman, E. ; Staikin, K. ; Hadar, Y. ; Friedler, A. ; Amartely, H. ; Slutzki, M. ; Di Pizio, A. ; Niv, M. Y. ; et al. Recombinant Ostreolysin Induces Brown Fat-Like Phenotype In Hib-1B Cells. Mol Nutr Food Res 2017, 61.Abstract
SCOPE: Brown adipose tissue (BAT) is the main regulator of thermogenesis by increasing energy expenditure through the uncoupling of oxidative metabolism from ATP synthesis. There is a growing body of evidence for BAT being the key responsible organ in combating obesity and its related disorders. Herein we propose the fungal protein ostreolysin (Oly), which has been previously shown to bind to cholesterol-enriched raft-like membrane domains (lipid rafts) of mammalian cells, as a suitable candidate for interaction with brown preadipocytes. The aim of the present study was therefore to characterize the mechanism by which a recombinant version of ostreolysin (rOly) induces brown adipocyte differentiation. METHODS AND RESULTS: Primary isolated brown preadipocytes or HIB-1B brown preadipocyte cells were treated with rOly and the effects on morphology, lipid accumulation, respiration rate, and associated gene and protein expression were measured. rOly upregulated mRNA and protein levels of factors related to brown adipocyte differentiation, induced lipid droplet formation, and increased cellular respiration rate due to expression of uncoupling protein 1. rOly also upregulated β-tubulin expression, and therefore microtubules might be involved in its mechanism of action. CONCLUSION: rOly promotes brown adipocyte differentiation, suggesting a new mechanism for rOly's contribution to the battle against obesity.
Oren, T. ; Nimri, L. ; Yehuda-Shnaidman, E. ; Staikin, K. ; Hadar, Y. ; Friedler, A. ; Amartely, H. ; Slutzki, M. ; Di Pizio, A. ; Niv, M. Y. ; et al. Recombinant Ostreolysin Induces Brown Fat-Like Phenotype In Hib-1B Cells. Molecular Nutrition & Food ResearchMolecular Nutrition & Food ResearchMol. Nutr. Food Res. 2017, 61, 1700057. Publisher's VersionAbstract
Scope Brown adipose tissue (BAT) is the main regulator of thermogenesis by increasing energy expenditure through the uncoupling of oxidative metabolism from ATP synthesis. There is a growing body of evidence for BAT being the key responsible organ in combating obesity and its related disorders. Herein we propose the fungal protein ostreolysin (Oly), which has been previously shown to bind to cholesterol-enriched raft-like membrane domains (lipid rafts) of mammalian cells, as a suitable candidate for interaction with brown preadipocytes. The aim of the present study was therefore to characterize the mechanism by which a recombinant version of ostreolysin (rOly) induces brown adipocyte differentiation. Methods and results Primary isolated brown preadipocytes or HIB-1B brown preadipocyte cells were treated with rOly and the effects on morphology, lipid accumulation, respiration rate, and associated gene and protein expression were measured. rOly upregulated mRNA and protein levels of factors related to brown adipocyte differentiation, induced lipid droplet formation, and increased cellular respiration rate due to expression of uncoupling protein 1. rOly also upregulated ?-tubulin expression, and therefore microtubules might be involved in its mechanism of action. Conclusion rOly promotes brown adipocyte differentiation, suggesting a new mechanism for rOly's contribution to the battle against obesity.
Slutzki, M. ; Ben-Shimon, A. ; Niv, M. Y. . Anchordock For Blind Flexible Docking Of Peptides To Proteins. In Modeling Peptide-Protein Interactions: Methods and Protocols; Schueler-Furman, O. ; London, N., Eds.; Springer New York: New York, NY, 2017; pp. 95–108. Publisher's VersionAbstract
Due to increasing interest in peptides as signaling modulators and drug candidates, several methods for peptide docking to their target proteins are under active development. The ``blind'' docking problem, where the peptide-binding site on the protein surface is unknown, presents one of the current challenges in the field. AnchorDock protocol was developed by Ben-Shimon and Niv to address this challenge.
Cheled-Shoval, S. ; Behrens, M. ; Korb, A. ; Di Pizio, A. ; Meyerhof, W. ; Uni, Z. ; Niv, M. Y. . From Cell To Beak: In-Vitro And In-Vivo Characterization Of Chicken Bitter Taste Thresholds. Molecules 2017, 22.Abstract
Bitter taste elicits an aversive reaction, and is believed to protect against consuming poisons. Bitter molecules are detected by the Tas2r family of G-protein-coupled receptors, with a species-dependent number of subtypes. Chickens demonstrate bitter taste sensitivity despite having only three bitter taste receptors-ggTas2r1, ggTas2r2 and ggTas2r7. This minimalistic bitter taste system in chickens was used to determine relationships between in-vitro (measured in heterologous systems) and in-vivo (behavioral) detection thresholds. ggTas2r-selective ligands, nicotine (ggTas2r1), caffeine (ggTas2r2), erythromycin and (+)-catechin (ggTas2r7), and the Tas2r-promiscuous ligand quinine (all three ggTas2rs) were studied. Ligands of the same receptor had different in-vivo:in-vitro ratios, and the ggTas2r-promiscuous ligand did not exhibit lower in-vivo:in-vitro ratios than ggTas2r-selective ligands. In-vivo thresholds were similar or up to two orders of magnitude higher than the in-vitro ones.
Cheled-Shoval, S. L. ; Reicher, N. ; Niv, M. Y. ; Uni, Z. . Detecting Thresholds For Bitter, Umami, And Sweet Tastants In Broiler Chicken Using A 2-Choice Test Method. Poultry Science 2017, 96, 2206 - 2218. Publisher's VersionAbstract
The sense of taste has a key role in nutrient sensing and food intake in animals. A standardized and simple method for determination of tastant-detection thresholds is required for chemosensory research in poultry. We established a 24-h, 2-alternative, forced-choice solution-consumption method and applied it to measure detection thresholds for 3 G-protein-coupled receptor-mediated taste modalities—bitter, sweet, and umami—in chicken. Four parameters were used to determine a significant response: 1) tastant-solution consumption; 2) water (tasteless) consumption; 3) total consumption (tastant and water together); 4) ratio of tastant consumption to total consumption. Our results showed that assignment of the taste solutions and a water control to 2 bottles on random sides of the pen can be reliably used for broiler chicks, even though 47% of the chicks groups demonstrated a consistently preferred side. The detection thresholds for quinine (bitter), L-monosodium glutamate (MSG) (umami), and sucrose (sweet) were determined to be 0.3 mM, 300 mM, and 1 M, respectively. The threshold results for quinine were similar to those for humans and rodents, but the chicks were found to be less sensitive to sucrose and MSG. The described method is useful for studying detection thresholds for tastants that have the potential to affect feed and water consumption in chickens.
Oren, T. ; Nimri, L. ; Yehuda-Shnaidman, E. ; Staikin, K. ; Hadar, Y. ; Friedler, A. ; Amartely, H. ; Slutzki, M. ; Di Pizio, A. ; Niv, M. Y. ; et al. Recombinant Ostreolysin Induces Brown Fat-Like Phenotype In Hib-1B Cells. Molecular Nutrition & Food Research 2017, 61, 1700057. Publisher's VersionAbstract
Scope Brown adipose tissue (BAT) is the main regulator of thermogenesis by increasing energy expenditure through the uncoupling of oxidative metabolism from ATP synthesis. There is a growing body of evidence for BAT being the key responsible organ in combating obesity and its related disorders. Herein we propose the fungal protein ostreolysin (Oly), which has been previously shown to bind to cholesterol-enriched raft-like membrane domains (lipid rafts) of mammalian cells, as a suitable candidate for interaction with brown preadipocytes. The aim of the present study was therefore to characterize the mechanism by which a recombinant version of ostreolysin (rOly) induces brown adipocyte differentiation. Methods and results Primary isolated brown preadipocytes or HIB-1B brown preadipocyte cells were treated with rOly and the effects on morphology, lipid accumulation, respiration rate, and associated gene and protein expression were measured. rOly upregulated mRNA and protein levels of factors related to brown adipocyte differentiation, induced lipid droplet formation, and increased cellular respiration rate due to expression of uncoupling protein 1. rOly also upregulated β-tubulin expression, and therefore microtubules might be involved in its mechanism of action. Conclusion rOly promotes brown adipocyte differentiation, suggesting a new mechanism for rOly's contribution to the battle against obesity.
Dubovski, N. ; Ert, E. ; Niv, M. Y. . Bitter Mouth-Rinse Affects Emotions. Food Quality and Preference 2017, 60, 154 - 164. Publisher's VersionAbstract
The sense of taste enables evaluation of food and is an important regulator of food consumption. In general, sweet is an attractive taste modality that leads to ingestion of nutritive food, while sour and bitter are aversive taste modalities that lead to avoidance of spoiled and toxic food. Recent studies suggest inter-connections between taste, emotion and cognition. Here we test the potential effects of two prototypical taste modalities, bitter and sweet, on emotions and on generalized avoidance behaviors, such as risk aversion and mistrust. Three experiments included over 250 participants who tasted, without swallowing, one of the following stimuli: water control, quinine solution, sucrose solution, quinine-sucrose mixture solution, or propylthiouracil (PROP) solution. The participants had to identify the taste, rank its intensity, perform seemingly unrelated behavioral tasks, and fill a PANAS mood questionnaire. Our results indicate that oral exposure to bitter compounds negatively correlates with mood scores; that the effect depends on perceiving the solution as bitter; that bitter mouth rinse can lower PANAS mood score and that there is a potential asymmetry in the effects of bitter and sweet taste modalities on mood.
Dagan-Wiener, A. ; Nissim, I. ; Ben Abu, N. ; Borgonovo, G. ; Bassoli, A. ; Niv, M. Y. . Bitter Or Not? Bitterpredict, A Tool For Predicting Taste From Chemical Structure. 2017, 7, 12074. Publisher's VersionAbstract
Bitter taste is an innately aversive taste modality that is considered to protect animals from consuming toxic compounds. Yet, bitterness is not always noxious and some bitter compounds have beneficial effects on health. Hundreds of bitter compounds were reported (and are accessible via the BitterDB http://bitterdb.agri.huji.ac.il/dbbitter.php), but numerous additional bitter molecules are still unknown. The dramatic chemical diversity of bitterants makes bitterness prediction a difficult task. Here we present a machine learning classifier, BitterPredict, which predicts whether a compound is bitter or not, based on its chemical structure. BitterDB was used as the positive set, and non-bitter molecules were gathered from literature to create the negative set. Adaptive Boosting (AdaBoost), based on decision trees machine-learning algorithm was applied to molecules that were represented using physicochemical and ADME/Tox descriptors. BitterPredict correctly classifies over 80% of the compounds in the hold-out test set, and 70–90% of the compounds in three independent external sets and in sensory test validation, providing a quick and reliable tool for classifying large sets of compounds into bitter and non-bitter groups. BitterPredict suggests that about 40% of random molecules, and a large portion (66%) of clinical and experimental drugs, and of natural products (77%) are bitter.