Publications by year

<embed>

Publications by Authors

Recent Publications

More<embed>

Contact Us

Head of Institute: Prof. Oren Froy

Administrative manager: Ms. Yael Fruchter

Office Address:
Institute of Biochemistry, Food Science and Nutrition,
Robert H. Smith Faculty of Agriculture, Food and Environment,
The Hebrew University of Jerusalem, 
P.O.Box 12, Rehovot 7610001, ISRAEL

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

Publications

2020
Ben Abu, N. ; Mason, P. E. ; Klein, H. ; Dubovski, N. ; Ben Shoshan-Galeczki, Y. ; Malach, E. ; Prazienkova, V. ; Maletinska, L. ; Tempra, C. ; Chamorro, V. C. ; et al. Sweet taste of heavy water. bioRxiv 2020. Publisher's VersionAbstract
Hydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish D2O from H2O by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and adds to perceived sweetness of sweeteners. In contrast, mice do not prefer D2O over H2O, indicating that they are not likely to perceive heavy water as sweet. For humans, the sweet taste of D2O is suppressed by lactisole, which is a known sweetness inhibitor acting via the TAS1R3 monomer of the TAS1R2/TAS1R3 sweet taste receptor. HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and the chimeric Gα16gust44 G-protein are activated by D2O but not by H2O. The present study resolves a long-standing controversy about the taste of heavy water, confirms that its sweet taste is mediated by the human TAS1R2/TAS1R3 taste receptor, and opens way to future studies of potential sites and modes of action.Competing Interest StatementThe authors have declared no competing interest.
Parma, V. ; Ohla, K. ; Veldhuizen, M. G. ; Niv, M. Y. ; Kelly, C. E. ; Bakke, A. J. ; Cooper, K. W. ; Bouysset, C. ; Pirastu, N. ; Dibattista, M. ; et al. More than just smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis. medRxiv 2020. Publisher's VersionAbstract
Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, generally lacked quantitative measurements, and were mostly restricted to data from single countries. Here, we report the development, implementation and initial results of a multi-lingual, international questionnaire to assess self-reported quantity and quality of perception in three distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, 8 other, ages 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7±28.7, mean±SD), taste (-69.0±32.6), and chemesthetic (-37.3±36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell, but also affects taste and chemesthesis. The multimodal impact of COVID-19 and lack of perceived nasal obstruction suggest that SARS-CoV-2 infection may disrupt sensory-neural mechanisms.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported financially with discretionary funds from the Pennsylvania State University (Penn State), including a gift from James and Helen Zallie given in support of Sensory Science at Penn State.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe data will be available at the OSF project: osf.io/a3vkwhttp://osf.io/a3vkw
Asseo, K. ; Fierro, F. ; Slavutsky, Y. ; Frasnelli, J. ; Niv, M. Y. Utility and limitations of Google searches on sensory loss as markers for new COVID-19 cases. medRxiv 2020. Publisher's VersionAbstract
Evidence of smell loss in COVID-19 is growing. Researchers and analysts have suggested to use Google searches on smell loss as indicators of COVID-19 cases. However, such searches may be due to interest elicited by media coverage of the COVID-19-related smell loss, rather than attempts to understand self-symptoms. We analyzed searches related to 4 senses: smell and taste (both recently shown to be impaired in some COVID-19 patients), vision and sight (senses not currently known to be impaired in COVID-19 patients), and an additional general control (“COVID-19 symptoms”). Focusing on two countries with a large number of cases, Italy and the United States, we have compared Google Trends results per region or state to the number of new cases prevalence in that region. The analysis was performed for each of the 8 weeks ranging from March 4th till April 28th. No correlation with vision loss or sight loss searches was identified, while taste and smell loss searches were correlated with new COVID-19 cases during a limited time window, that starts when the number of weekly new cases reached for the first time 21357 cases in Italy (11-17 March) and 47553 in the US (18-24 March). Media effect on the specific symptoms searches was also analyzed, establishing a different impact according to the country. Our results suggest that Google Trends for taste loss and smell loss searches captured a genuine connection between these symptoms and new COVID-19 cases prevalence in the population. However, due to variability in correlation from week to week, and overall decrease in correlation as taste and smell loss are becoming known COVID-19 symptoms, recognized now by CDC and World Health Organization, Google Trends is no longer a reliable marker for monitoring the disease spread. The “surprise rise” followed by decrease, probably attributable to knowledge saturation, should be kept in mind for future digital media analyses of potential new symptoms of COVID-19 or future pandemics.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by the ISF grant #1129/19Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData will be made available on GitHub
Shoshan-Galeczki], Y. [B. ; Niv, M. Y. Structure-based screening for discovery of sweet compounds. Food Chemistry 2020, 315, 126286. Publisher's VersionAbstract
Sweet taste is a cue for calorie-rich food and is innately attractive to animals, including humans. In the context of modern diets, attraction to sweetness presents a significant challenge to human health. Most known sugars and sweeteners bind to the Venus Fly Trap domain of T1R2 subunit of the sweet taste heterodimer. Because the sweet taste receptor structure has not been experimentally solved yet, a possible approach to finding sweet molecules is virtual screening using compatibility of candidate molecules to homology models of sugar-binding site. Here, the constructed structural models, docking and scoring schemes were validated by their ability to rank known sweet-tasting compounds higher than properties-matched random molecules. The best performing models were next used in virtual screening, retrieving recently patented sweeteners and providing novel predictions.
Leung, N. Y. ; Thakur, D. P. ; Gurav, A. S. ; Kim, S. H. ; Pizio], A. [D. ; Niv, M. Y. ; Montell, C. Functions of Opsins in Drosophila Taste. Current Biology 2020, 30, 1367 - 1379.e6. Publisher's VersionAbstract
Summary Rhodopsin is a light receptor comprised of an opsin protein and a light-sensitive retinal chromophore. Despite more than a century of scrutiny, there is no evidence that opsins function in chemosensation. Here, we demonstrate that three Drosophila opsins, Rh1, Rh4, and Rh7, are needed in gustatory receptor neurons to sense a plant-derived bitter compound, aristolochic acid (ARI). The gustatory requirements for these opsins are light-independent and do not require retinal. The opsins enabled flies to detect lower concentrations of aristolochic acid by initiating an amplification cascade that includes a G-protein, phospholipase Cβ, and the TRP channel, TRPA1. In contrast, responses to higher levels of the bitter compound were mediated through direct activation of TRPA1. Our study reveals roles for opsins in chemosensation and raise questions concerning the original roles for these classical G-protein-coupled receptors.
Littmann, M. ; Selig, K. ; Cohen-Lavi, L. ; Frank, Y. ; Hönigschmid, P. ; Kataka, E. ; Mösch, A. ; Qian, K. ; Ron, A. ; Schmid, S. ; et al. Validity of machine learning in biology and medicine increased through collaborations across fields of expertise. 2020, 2 18 - 24. Publisher's VersionAbstract
Machine learning (ML) has become an essential asset for the life sciences and medicine. We selected 250 articles describing ML applications from 17 journals sampling 26 different fields between 2011 and 2016. Independent evaluation by two readers highlighted three results. First, only half of the articles shared software, 64% shared data and 81% applied any kind of evaluation. Although crucial for ensuring the validity of ML applications, these aspects were met more by publications in lower-ranked journals. Second, the authors’ scientific backgrounds highly influenced how technical aspects were addressed: reproducibility and computational evaluation methods were more prominent with computational co-authors; experimental proofs more with experimentalists. Third, 73% of the ML applications resulted from interdisciplinary collaborations comprising authors from at least two of the three disciplines: computational sciences, biology, and medicine. The results suggested collaborations between computational and experimental scientists to generate more scientifically sound and impactful work integrating knowledge from both domains. Although scientifically more valid solutions and collaborations involving diverse expertise did not correlate with impact factors, such collaborations provide opportunities to both sides: computational scientists are given access to novel and challenging real-world biological data, increasing the scientific impact of their research, and experimentalists benefit from more in-depth computational analyses improving the technical correctness of work.
Di Pizio, A. ; Waterloo, L. A. W. ; Brox, R. ; Löber, S. ; Weikert, D. ; Behrens, M. ; Gmeiner, P. ; Niv, M. Y. Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back. Cell Mol Life Sci 2020, 77, 531-542.Abstract
Human bitter taste receptors (TAS2Rs) are a subfamily of 25 G protein-coupled receptors that mediate bitter taste perception. TAS2R14 is the most broadly tuned bitter taste receptor, recognizing a range of chemically diverse agonists with micromolar-range potency. The receptor is expressed in several extra-oral tissues and is suggested to have physiological roles related to innate immune responses, male fertility, and cancer. Higher potency ligands are needed to investigate TAS2R14 function and to modulate it for future clinical applications. Here, a structure-based modeling approach is described for the design of TAS2R14 agonists beginning from flufenamic acid, an approved non-steroidal anti-inflammatory analgesic that activates TAS2R14 at sub-micromolar concentrations. Structure-based molecular modeling was integrated with experimental data to design new TAS2R14 agonists. Subsequent chemical synthesis and in vitro profiling resulted in new TAS2R14 agonists with improved potency compared to the lead. The integrated approach provides a validated and refined structural model of ligand-TAS2R14 interactions and a general framework for structure-based discovery in the absence of closely related experimental structures.
Stoeger, V. ; Holik, A. - K. ; Hölz, K. ; Dingjan, T. ; Hans, J. ; Ley, J. P. ; Krammer, G. E. ; Niv, M. Y. ; Somoza, M. M. ; Somoza, V. Bitter-Tasting Amino Acids l-Arginine and l-Isoleucine Differentially Regulate Proton Secretion via T2R1 Signaling in Human Parietal Cells in Culture. J Agric Food Chem 2020, 68, 3434-3444.Abstract
This study aimed at identifying whether the bitter-tasting amino acids l-arginine (l-ARG) and l-isoleucine (l-ILE) differentially regulate mechanisms of gastric acid secretion in human parietal cells (HGT-1 cells) via activation of bitter taste sensing receptors (T2Rs). In a first set of experiments, involvement of T2Rs in l-ARG and l-ILE-modulated proton secretion was demonstrated by co-treatment of HGT-1 cells with T2R antagonists. Subsequent whole genome screenings by means of cDNA arrays revealed T2R1 as a prominent target for both amino acids. Next, the functional role of T2R1 was verified by means of a CRISPR-Cas9 knock-out approach. Here, the effect of l-ARG on proton secretion decreased by 65.7 ± 21.9% and the effect of l-ILE increased by 93.2 ± 24.1% in HGT-1 T2R1 ko versus HGT-1 wt cells ( < 0.05). Overall, our results indicate differential effects of l-ARG and l-ILE on proton secretion in HGT-1 cells and our molecular docking studies predict distinct binding for these amino acids in the binding site of T2R1. Further studies will elucidate whether the mechanism of differential effects involves structure-specific ligand-biased signaling of T2R1 or additional cellular targets.
Cruces-Sande, M. ; Arcones, A. C. ; Vila-Bedmar, R. ; Val-Blasco, A. ; Sharabi, K. ; Díaz-Rodríguez, D. ; Puigserver, P. ; Mayor, F. ; Murga, C. Autophagy mediates hepatic GRK2 degradation to facilitate glucagon-induced metabolic adaptation to fasting. FASEB J 2020, 34, 399-409.Abstract
The liver plays a key role during fasting to maintain energy homeostasis and euglycemia via metabolic processes mainly orchestrated by the insulin/glucagon ratio. We report here that fasting or calorie restriction protocols in C57BL6 mice promote a marked decrease in the hepatic protein levels of G protein-coupled receptor kinase 2 (GRK2), an important negative modulator of both G protein-coupled receptors (GPCRs) and insulin signaling. Such downregulation of GRK2 levels is liver-specific and can be rapidly reversed by refeeding. We find that autophagy, and not the proteasome, represents the main mechanism implicated in fasting-induced GRK2 degradation in the liver in vivo. Reducing GRK2 levels in murine primary hepatocytes facilitates glucagon-induced glucose production and enhances the expression of the key gluconeogenic enzyme Pck1. Conversely, preventing full downregulation of hepatic GRK2 during fasting using adenovirus-driven overexpression of this kinase in the liver leads to glycogen accumulation, decreased glycemia, and hampered glucagon-induced gluconeogenesis, thus preventing a proper and complete adaptation to nutrient deprivation. Overall, our data indicate that physiological fasting-induced downregulation of GRK2 in the liver is key for allowing complete glucagon-mediated responses and efficient metabolic adaptation to fasting in vivo.
Ben-Yacov, L. ; Ainembabazi, P. ; Stark, A. H. ; Kizito, S. ; Bahendeka, S. Prevalence and sex-specific patterns of metabolic syndrome in rural Uganda. BMJ Nutrition, Prevention & Health 2020. Publisher's VersionAbstract
{Background and aims In sub-Saharan Africa, infectious diseases are still the leading causes of mortality; however, this may soon be surpassed by non-communicable illnesses, namely hypertension, diabetes and cardiovascular disease. This study determined the prevalence and patterns of metabolic syndrome and cardio-risk factors in men and women in rural Uganda.Methods A household-based, cross-sectional survey was carried out following the WHO STEP-wise approach to surveillance. It included demographic and lifestyle questionnaires, anthropometric measurements and biochemical analyses. Of the 200 randomly recruited participants, 183 successfully completed two steps of the study and 161 provided blood samples.Results Data were collected from 183 adults, aged 18–69 years; 62% were female. Based on the National Cholesterol Education Program-Adult Treatment Panel-III criteria, the prevalence of metabolic syndrome was 19.1% (95% CI 14.0 to 22.5). Elevated fasting plasma glucose was observed in 14.2% (95% CI 9.1 to 19.3) of participants, hypertriglyceridaemia in 16.9% (95% CI 12.1 to 23.1); hypertension in 36.1% (95% CI 29.0 to 43.0) and 52.5% (95% CI 45.2 to 59.6) had low HDL (high-density lipoprotein) cholesterol. Abdominal obesity was found in 24.6% (95% CI 18.8 to 31.4) of participants. Sex disparities were significant for several risk factors. Females had significantly higher prevalence of abdominal obesity (38.6% vs 1.5% in males