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Head of Institute: Prof. Oren Tirosh

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

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Email Address: rakefetk@savion.huji.ac.il

Publications

2021
Daniel, T. ; Ben-Shachar, M. ; Drori, E. ; Hamad, S. ; Permyakova, A. ; Ben-Cnaan, E. ; Tam, J. ; Kerem, Z. ; Rosenzweig, T. Grape pomace reduces the severity of non-alcoholic hepatic steatosis and the development of steatohepatitis by improving insulin sensitivity and reducing ectopic fat deposition in mice. JOURNAL OF NUTRITIONAL BIOCHEMISTRY 2021, 98.Abstract
While non-alcoholic fatty liver disease (NAFLD) represents the common cause of chronic liver disease, specific therapies are currently unavailable. The wine industry produces millions of tons of residue (pomace), which contains high levels of bioactive phytochemicals. The aim of this study was to clarify the potential benefits of grape pomace for the treatment of NAFLD at different levels of severity, and to clarify the mechanism of action. C57Bl/6 mice were given high fat diet (HFD) or western diet (WD) as models of obesity and hepatic steatosis or steatohepatitis, respectively, with or without pomace supplementation (50-250 mg/day). Pomace inhibited food intake, and reduced serum leptin and body weight gain. Ectopic fat deposition was reduced, while white adipose tissue mass was preserved. In addition, pomace improved glucose tolerance and insulin sensitivity, prevented the development of adipose tissue inflammation, and reduced hepatic steatosis. Higher expression of genes involved in fatty acids transport and oxidation was observed in adipose tissue, while lipogenic genes were attenuated in the liver of pomace-treated mice. In WD-fed mice, pomace reduced the severity of hepatic steatosis and inflammation and improved blood lipid profile, but was ineffective in reversing hepatic damage of advanced NASH. In conclusion, pomace improved insulin sensitivity and reduced ectopic fat deposition, leading to a healthier metabolic profile. Pomace may hold the potential as a supplement with beneficial health outcomes for the prevention and treatment of hepatic steatosis and other obesity-related pathologies. (c) 2021 Elsevier Inc. All rights reserved.
Friesem, G. ; Reznik, N. ; Cohen, M. S. ; Carmi, N. ; Kerem, Z. ; Yedidia, I. Root-Associated Microbiomes, Growth and Health of Ornamental Geophytes Treated with Commercial Plant Growth-Promoting Products. MICROORGANISMS 2021, 9.Abstract
The microbial community inhabiting a plant's root zone plays a crucial role in plant health and protection. To assess the ability of commercial plant growth-promoting products to enhance the positive effects of this environment, two products containing beneficial soil bacteria and a product containing plant extracts were tested on Zantedeschia aethiopica and Ornithogalum dubium. The products were tested in two different growing media: a soil and a soilless medium. The effects of these products on Pectobacterium brasiliense, the causal agent of soft rot disease, were also evaluated in vitro, and on naturally occurring infections in the greenhouse. The growing medium was found to have the strongest effect on the microbial diversity of the root-associated microbiome, with the next-strongest effect due to plant type. These results demonstrate that either a single bacterial strain or a product will scarcely reach the level that is required to influence soil microbial communities. In addition, the microbes cultured from these products, could not directly inhibit Pectobacterium growth in vitro. We suggest density-based and functional analyses in the future, to study the specific interactions between plants, soil type, soil microbiota and relevant pathogens. This should increase the effectiveness of bio-supplements and soil disinfestation with natural products, leading to more sustainable, environmentally friendly solutions for the control of bacterial plant diseases.
Guttman, Y. ; Joshi, J. R. ; Chriker, N. ; Khadka, N. ; Kleiman, M. ; Reznik, N. ; Wei, Z. ; Kerem, Z. ; Yedidia, I. Ecological adaptations influence the susceptibility of plants in the genus Zantedeschia to soft rot Pectobacterium spp. HORTICULTURE RESEARCH 2021, 8.Abstract
Soft rot disease caused by Pectobacterium spp. is responsible for severe agricultural losses in potato, vegetables, and ornamentals. The genus Zantedeschia includes two botanical groups of tuberous ornamental flowers that are highly susceptible to the disease. Previous studies revealed that Z. aethiopica, a member of the section Zantedeschia, is significantly more resistant to Pectobacterium spp. than members of the same genus that belong to the section Aestivae. During early infection, we found different patterns of bacterial colonization on leaves of hosts belonging to the different sections. Similar patterns of bacterial colonization were observed on polydimethylsiloxane (PDMS) artificial inert replicas of leaf surfaces. The replicas confirmed the physical effect of leaf texture, in addition to a biochemical plant-bacterium interaction. The differential patterns may be associated with the greater roughness of the abaxial leaf surfaces of Aestivae group that have evolutionarily adapted to mountainous environments, as compared to Zantedeschia group species that have adapted to warm, marshy environments. Transverse leaf sections also revealed compact aerenchyma and reduced the total volume of leaf tissue air spaces in Aestivae members. Finally, an analysis of defense marker genes revealed differential expression patterns in response to infection, with significantly higher levels of lipoxygenase 2 (lox2) and phenylalanine ammonia lyase (pal) observed in the more resistant Z. aethiopica, suggesting greater activation of induced systemic resistance (ISR) mechanisms in this group. The use of Zantedeschia as a model plant sheds light on how natural ecological adaptations may underlay resistance to bacterial soft rot in cultivated agricultural environments.
Pun, M. ; Khazanov, N. ; Galsurker, O. ; Weitman, M. ; Kerem, Z. ; Senderowitz, H. ; Yedidia, I. Phloretin, an Apple Phytoalexin, Affects the Virulence and Fitness of Pectobacterium brasiliense by Interfering With Quorum-Sensing. FRONTIERS IN PLANT SCIENCE 2021, 12.Abstract
The effects of phloretin a phytoalexin from apple, was tested on Pectobacterium brasiliense (Pb1692), an emerging soft-rot pathogen of potato. Exposure of Pb1692 to 0.2 mM phloretin a concentration that does not affect growth, or to 0.4 mM a 50% growth inhibiting concentration (50% MIC), reduced motility, biofilm formation, secretion of plant cell wall-degrading enzymes, production of acyl-homoserine lactone (AHL) signaling molecules and infection, phenotypes that are associated with bacterial population density-dependent system known as quorum sensing (QS). To analyze the effect of growth inhibition on QS, the activity of ciprofloxacin, an antibiotic that impairs cell division, was compared to that of phloretin at 50% MIC. Unlike phloretin, the antibiotic hardly affected the tested phenotypes. The use of DH5 alpha, a QS-negative Escherichia coli strain, transformed with an AHL synthase (ExpI) from Pb1692, allowed to validate direct inhibition of AHL production by phloretin, as demonstrated by two biosensor strains, Chromobacterium violaceaum (CV026) and E. coli (pSB401). Expression analysis of virulence-related genes revealed downregulation of QS-regulated genes (expI, expR, luxS, rsmB), plant cell wall degrading enzymes genes (pel, peh and prt) and motility genes (motA, fim, fliA, flhC and flhD) following exposure to both phloretin concentrations. The results support the inhibition of ExpI activity by phloretin. Docking simulations were used to predict the molecular associations between phloretin and the active site of ExpI, to suggest a likely mode of action for the compound's inhibition of virulence.
2020
Milenkovic, D. ; Declerck, K. ; Guttman, Y. ; Kerem, Z. ; Claude, S. ; Weseler, A. R. ; Bast, A. ; Schroeter, H. ; Morand, C. ; Vanden Berghe, W. (-)-Epicatechin metabolites promote vascular health through epigenetic reprogramming of endothelial-immune cell signaling and reversing systemic low-grade inflammation. BIOCHEMICAL PHARMACOLOGY 2020, 173.Abstract
Ingestion of (-)-epicatechin flavanols reverses endothelial dysfunction by increasing flow mediated dilation and by reducing vascular inflammation and oxidative stress, monocyte-endothelial cell adhesion and transendothelial monocyte migration in vitro and in vivo. This involves multiple changes in gene expression and epigenetic DNA methylation by poorly understood mechanisms. By in silico docking and molecular modeling we demonstrate favorable binding of different glucuronidated, sulfated or methylated (-)-epicatechin metabolites to different DNA methyltransferases (DNMT1/DNMT3A). In favor of this model, genome-wide DNA methylation profiling of endothelial cells treated with TNF and different (-)-epicatechin metabolites revealed specific DNA methylation changes in gene networks controlling cell adhesion-extravasation endothelial hyperpermeability as well as gamma-aminobutyric acid, renin-angiotensin and nitric oxide hypertension pathways. Remarkably, blood epigenetic profiles of an 8 weeks intervention with monomeric and oligomeric flavanols (MOF) including (-)-epicatechin in male smokers revealed individual epigenetic gene changes targeting similar pathways as the in vitro exposure experiments in endothelial cells. Furthermore, epigenetic changes following MOF diet intervention oppose atherosclerosis associated epigenetic changes. In line with biological data, the individual epigenetic response to a MOF diet is associated with different vascular health parameters (glutathione peroxidase 1 and endothelin-1 expression, acetylcholine-mediated microvascular response), in part involving systemic shifts in blood immune cell types which reduce the neutrophil-lymphocyte ratio (NLR). Altogether, our study suggests that different (-)-epicatechin metabolites promote vascular health in part via epigenetic reprogramming of endothelial-immune cell signaling and reversing systemic low-grade inflammation.
Nissim, Y. ; Shlosberg, M. ; Biton, I. ; Many, Y. ; Doron-Faigenboim, A. ; Hovav, R. ; Kerem, Z. ; Avidan, B. ; Ben-Ari, G. A High Temperature Environment Regulates the Olive Oil Biosynthesis Network. PLANTS-BASEL 2020, 9.Abstract
Climate change has been shown to have a substantial impact on agriculture and high temperatures and heat stress are known to have many negative effects on the vegetative and reproductive phases of plants. In a previous study, we addressed the effects of high temperature environments on olive oil yield and quality, by comparing the fruit development and oil accumulation and quality of five olive cultivars placed in high temperature and moderate temperature environments. The aim of the current study was to explore the molecular mechanism resulting in the negative effect of a high temperature environment on oil quantity and quality. We analyzed the transcriptome of two extreme cultivars, `Barnea', which is tolerant to high temperatures in regard to quantity of oil production, but sensitive regarding its quality, and `Souri', which is heat sensitive regarding quantity of oil produced, but relatively tolerant regarding its quality. Transcriptome analyses have been carried out at three different time points during fruit development, focusing on the genes involved in the oil biosynthesis pathway. We found that heat-shock protein expression was induced by the high temperature environment, but the degree of induction was cultivar dependent. The `Barnea' cultivar, whose oil production showed greater tolerance to high temperatures, exhibited a larger degree of induction than the heat sensitive `Souri'. On the other hand, many genes involved in olive oil biosynthesis were found to be repressed as a response to high temperatures.OePDCTas well asOeFAD2 genes showed cultivar dependent expression patterns according to their heat tolerance characteristics. The transcription factors OeDof4.3, OeWRI1.1, OeDof4.4 and OeWRI1.2 were identified as key factors in regulating the oil biosynthesis pathway in response to heat stress, based on their co-expression characteristics with other genes involved in this pathway. Our results may contribute to identifying or developing a more heat tolerant cultivar, which will be able to produce high yield and quality oil in a future characterized by global warming.
Khadka, N. ; Joshi, J. R. ; Reznik, N. ; Chriker, N. ; Nudel, A. ; Zelinger, E. ; Kerem, Z. ; Yedidia, I. Host Specificity and Differential Pathogenicity of Pectobacterium Strains from Dicot and Monocot Hosts. MICROORGANISMS 2020, 8.Abstract
Recent phylogenetic studies have transferred certain isolates from monocot plants previously included in the heterogeneous group of Pectobacterium carotovorum (Pc) to a species level termed Pectobacterium aroidearum. The specificity of Pectobacterium associated infections had received less attention, and may be of high scientific and economic importance. Here, we have characterized differential responses of Pectobacterium isolates from potato (WPP14) and calla lily (PC16) on two typical hosts: Brassica oleracea var. capitata (cabbage) a dicot host; and Zantedeschia aethiopica (calla lily) a monocot host. The results revealed clear host specific responses following infection with the two bacterial strains. This was demonstrated by differential production of volatile organic compounds (VOCs) and the expression of plant defense-related genes (pal, PR-1, lox2, ast). A related pattern was observed in bacterial responses to each of the host's extract, with differential expression of virulence-related determinants and genes associated with quorum-sensing and plant cell wall-degrading enzymes. The differences were associated with each strain's competence on its respective host.
Nissim, Y. ; Shloberg, M. ; Biton, I. ; Many, Y. ; Doron-Faigenboim, A. ; Zemach, H. ; Hovav, R. ; Kerem, Z. ; Avidan, B. ; Ben-Ari, G. High temperature environment reduces olive oil yield and quality. PLOS ONE 2020, 15.Abstract
Global warming is predicted to have a negative effect on plant growth due to the damaging effect of high temperatures. In order to address the effect of high temperature environments on olive oil yield and quality, we compared its effect on the fruit development of five olive cultivars placed in a region noted for its high summer temperatures, with trees of the same cultivars placed in a region of relatively mild summers. We found that the effects of a high temperature environment are genotype dependent and in general, high temperatures during fruit development affected three important traits: fruit weight, oil concentration and oil quality. None of the tested cultivars exhibited complete heat stress tolerance. Final dry fruit weight at harvest of the `Barnea' cultivar was not affected by the high temperature environment, whereas the `Koroneiki', `Coratina', `Souri' and `Picholine' cultivars exhibited decreased dry fruit weight at harvest in response to higher temperatures by 0.2, 1, 0.4 and 0.2 g respectively. The pattern of final oil concentration was also cultivar dependent, `Barnea', `Coratina' and `Picholine' not being affected by the high temperature environment, whereas the `Koroneiki' and `Souri' cultivars showed a decreased dry fruit oil concentration at harvest under the same conditions by 15 and 8% respectively. Regarding the quality of oil produced, the `Souri' cultivar proved more tolerant to a high temperature environment than any other of the cultivars analyzed in this study. These results suggest that different olive cultivars have developed a variety of mechanisms in dealing with high temperatures. Elucidation of the mechanism of each of these responses may open the way to development of a variety of olives broadly adapted to conditions of high temperatures.
Yedidia, I. ; Kerem, Z. ; Pun, M. Potentiation of plant-derived anti-quorum sensing compounds. PHYTOPATHOLOGY 2020, 110, 188.
Guttman, Y. ; Yedidia, I. ; Nudel, A. ; Zhmykhova, Y. ; Kerem, Z. ; Carmi, N. New grapefruit cultivars exhibit low cytochrome P4503A4-Inhibition activity. FOOD AND CHEMICAL TOXICOLOGY 2020, 137.Abstract
Furanocoumarins are the main compounds responsible for the food-drug interactions known as the grapefruit effect, which is caused by the inhibition of CYP3A4-mediated drug metabolism. We evaluated the effects of two new, low-furanocoumarin grapefruit cultivars on CYP3A4 activity and the roles of different furanocoumarins, individually and together with other juice compounds, in the inhibition of CYP3A4 by grapefruit. Whereas a standard grapefruit cultivar inhibited CYP3A4 activity in a dose-dependent manner, neither of the two examined low-furanocoumarin cultivars had an inhibitory effect. Despite the fact that bergamottin and 6',7'-dihydroxybergamottin are weak inhibitors of CYP3A4, their relatively high levels in grapefruit make them the leading cause of the grapefruit effect. We found that furanocoumarins together with other juice compounds inhibit CYP3A4 in an additive manner. In silico docking simulation was employed, and differentiated between high- and low-potency inhibitors, suggesting that modeling may be useful for identifying potentially harmful food-drug interactions.
2019
Basheer, L. ; Dag, A. ; Yermiyahu, U. ; Ben-Gal, A. ; Zipori, I. ; Kerem, Z. Effects of reclaimed wastewater irrigation and fertigation level on olive oil composition and quality. Journal of the Science of Food and Agriculture 2019, 99, 6342-6349. Publisher's VersionAbstract
BACKGROUND: Irrigation of olives increases fruit and oil yields. Due to scarcity of freshwater, low-quality water including recycled wastewater (RWW) is utilized in orchards. Here, effects of irrigation with RWW and of fertilization on the composition and quality of olive oil were studied. RESULTS: Long-term RWW irrigation of ‘Barnea’ and ‘Leccino’ olive had no significant negative effects on either oil composition or quality parameters, including free fatty acids (FFAs), peroxide value (PV), total phenolics content (TPC), fatty acid profiles and organoleptic characteristics. The average FFA contents for both cultivars were less than 0.8% during most of the experimental period, except the seasons 2009 and 2012–2013 for Barnea where the values were raised up to 1.4%. The measured PV levels were less than 9 and 5 mmol O2 kg-1 oil for Barnea and Leccino, respectively. In the last season of the experiment for each cultivar, higher TPC were observed in oils obtained from RWW irrigation with reduced fertilization (Re–) as compared to the treatments with the recommended fertilization [freshwater irrigation (Fr) and RWW irrigation (Re+) with standard dose of fertilizers], where the TPC increment exceeded 70% in Barnea and 25% in Leccino. The treatments had only minor effects on the fatty acid profile, reflected in slightly altered levels of C18:2 and C18:3 fatty acids. CONCLUSION: The use of RWW, combined with the consideration of nutrients arriving with such water to provide appropriate fertilization, was found suitable for olive irrigation to ensure optimal yields while preserving oil quality. © 2019 Society of Chemical Industry. © 2019 Society of Chemical Industry
Goldental-Cohen, S. ; Biton, I. ; Many, Y. ; Tavrizov, K. ; Dourou, A. M. ; Zemach, H. ; Tonutti, P. ; Kerem, Z. ; Avidan, B. ; Sperling, O. ; et al. Removal of flowers or inflorescences affects ‘Barnea’ olive fruitlet post-anthesis abscission. Journal of Horticultural Science and Biotechnology 2019, 94, 488-498. Publisher's VersionAbstract
A typical olive (Olea europaea L.) inflorescence consists of about 20 flowers. However, in many cultivars, only one fruit develops. This is due to massive abscission of flowers and fruitlets, which occurs during the first month after anthesis. In this study, we used the olive cultivar 'Barnea' to characterize the abscission mechanism and to try to increase fruit set by increasing the number of developed fruit per inflorescence. Removing the lateral flowers 3 weeks before anthesis increased fruit set by more than 50%. Removing all inflorescences but one from a branch increased the number of developed fruits from 0.93 to 2.8 during 2017 and from 0.91 to 3.34 fruits per inflorescence in 2018. Sugar quantification in the pistil revealed that starch level is high on the day of anthesis and low 25 days later in abscised as well as in developed fruit. Soluble carbohydrates are low on the day of anthesis, low in abscised flowers/fruitlets 25 days after anthesis and high in developed fruit. Screening the natural variation found in the Israeli germplasm collection revealed that in most cultivars less than one fruit per inflorescence has developed. However, there are unique cultivars with a higher fruit set. © 2018, © 2018 The Journal of Horticultural Science & Biotechnology Trust.
Yedidia, I. ; Schultz, K. ; Golan, A. ; Gottlieb, H. E. ; Kerem, Z. Structural elucidation of three novel kaempferol otri-glycosides that are involved in the defense response of hybrid ornithogalum to pectobacterium carotovorum. Molecules 2019, 24. Publisher's VersionAbstract
Ornithogalum is an ornamental flowering species that grows from a bulb and is highly susceptible to soft-rot disease caused by Pectobacterium carotovorum (Pc). Interspecific hybridization between O. thyrsoides and O. dubium yielded hybrids with enhanced resistance to that pathogen. The hybrids displayed distinct phenolic-compound profiles with several peaks that were specifically heightened following Pc infection. Three of these compounds were isolated and identified as novel kaempferol O-tri-glycosides. The structures of these compounds were elucidated using reversed phase high-performance liquid chromatography (RP-LC), RP-LC coupled to high-resolution mass spectrometry (RP-LC-MS), and nuclear magnetic resonance (NMR) (1D 1H and 13C, DEPT, HMQC, HMBC, COSY, and NOE), in order to achieve pure and defined compounds data. The new compounds were finally identified as kaempferol 3-O-[4-O-α-L-(3-O-acetic)-rhamnopyranosyl-6-O- β-D-xylopyranosyl]-β-D-glucopyranoside, kaempferol 3-O-[4-O-α-L-(2-O-acetic)-rhamnopyranosyl- 6-O-β-D-xylopyranosyl]-β-D-glucopyranoside and kaempferol 3-O-[4-O-α-L-(2,3-O-diacetic)- rhamnopyranosyl-6-O-β-D-xylopyranosyl]-β-D-glucopyranoside. © 2019 MDPI AG. All rights reserved.
de Roos, B. ; Aura, A. - M. ; Bronze, M. ; Cassidy, A. ; Conesa, M. - T. G. ; Gibney, E. R. ; Greyling, A. ; Kaput, J. ; Kerem, Z. ; Knežević, N. ; et al. Targeting the delivery of dietary plant bioactives to those who would benefit most: from science to practical applications. European Journal of Nutrition 2019, 58, 65-73. Publisher's VersionAbstract
Background: A healthy diet and optimal lifestyle choices are amongst the most important actions for the prevention of cardiometabolic diseases. Despite this, it appears difficult to convince consumers to select more nutritious foods. Furthermore, the development and production of healthier foods do not always lead to economic profits for the agro-food sector. Most dietary recommendations for the general population represent a “one-size-fits-all approach” which does not necessarily ensure that everyone has adequate exposure to health-promoting constituents of foods. Indeed, we now know that individuals show a high variability in responses when exposed to specific nutrients, foods, or diets. Purpose: This review aims to highlight our current understanding of inter-individual variability in response to dietary bioactives, based on the integration of findings of the COST Action POSITIVe. We also evaluate opportunities for translation of scientific knowledge on inter-individual variability in response to dietary bioactives, once it becomes available, into practical applications for stakeholders, such as the agro-food industry. The potential impact from such applications will form an important impetus for the food industry to develop and market new high quality and healthy foods for specific groups of consumers in the future. This may contribute to a decrease in the burden of diet-related chronic diseases. © 2019, The Author(s).
Milenkovic, D. ; Declerck, K. ; Guttman, Y. ; Kerem, Z. ; Claude, S. ; Weseler, A. R. ; Bast, A. ; Schroeter, H. ; Morand, C. ; Vandenberghe, W. (−)-Epicatechin metabolites promote vascular health through epigenetic reprogramming of endothelial-immune cell signaling and reversing systemic low-grade inflammation. Biochemical Pharmacology 2019. Publisher's VersionAbstract
Ingestion of (−)-epicatechin flavanols reverses endothelial dysfunction by increasing flow mediated dilation and by reducing vascular inflammation and oxidative stress, monocyte-endothelial cell adhesion and transendothelial monocyte migration in vitro and in vivo. This involves multiple changes in gene expression and epigenetic DNA methylation by poorly understood mechanisms. By in silico docking and molecular modeling we demonstrate favorable binding of different glucuronidated, sulfated or methylated (−)-epicatechin metabolites to different DNA methyltransferases (DNMT1/DNMT3A). In favor of this model, genome-wide DNA methylation profiling of endothelial cells treated with TNF and different (−)-epicatechin metabolites revealed specific DNA methylation changes in gene networks controlling cell adhesion-extravasation endothelial hyperpermeability as well as gamma-aminobutyric acid, renin-angiotensin and nitric oxide hypertension pathways. Remarkably, blood epigenetic profiles of an 8 weeks intervention with monomeric and oligomeric flavanols (MOF) including (−)-epicatechin in male smokers revealed individual epigenetic gene changes targeting similar pathways as the in vitro exposure experiments in endothelial cells. Furthermore, epigenetic changes following MOF diet intervention oppose atherosclerosis associated epigenetic changes. In line with biological data, the individual epigenetic response to a MOF diet is associated with different vascular health parameters (glutathione peroxidase 1 and endothelin-1 expression, acetylcholine-mediated microvascular response), in part involving systemic shifts in blood immune cell types which reduce the neutrophil–lymphocyte ratio (NLR). Altogether, our study suggests that different (−)-epicatechin metabolites promote vascular health in part via epigenetic reprogramming of endothelial-immune cell signaling and reversing systemic low-grade inflammation. © 2019 Elsevier Inc.
Guttman, Y. ; Nudel, A. ; Kerem, Z. Polymorphism in Cytochrome P450 3A4 Is Ethnicity Related. Front. Genet., 2019, 10, 224. Publisher's VersionAbstract
Can mutations in cytochrome P450 3A4 (CYP3A4), the major food- and drug-metabolizing enzyme, serve as biomarkers for personalized precise medicine? Classical genetic studies provide only limited data regarding the frequencies of CYP3A4 mutations and their role in food-drug interactions. Here, in an analysis of one large database of 141,456 individuals, we found 856 SNPs (single nucleotide polymorphism), of which 312 are missense mutations, far more than the previously reported dozens. Analyzing the data further, it is demonstrated that the frequency of mutations differs among ethnic groups. Hierarchical clustering divided the mutations into seven groups, each corresponding to a specific ethnicity. To the best of our knowledge, this is the first comprehensive analysis of CYP3A4 allele frequencies in distinct ethnic groups. We suggest ethnicity based classification of CYP3A4 SNPs as the first step towards precise diet and medicine. Understanding which and when polymorphism might have clinical significance is a tremendously complex task. Using a modeling approach, we could predict changes in the binding poses of ligands in the active site of single variants. These changes might imply clinical effects of the overlooked protein-altering CYP3A4 mutations, by modifying drug metabolism and FDI. It may be concluded that dietary habits, and hence FDI, are matters of ethnicity. Consequently, ethnic-related polymorphism in CYP3A4 and diet may be one underlying mechanism of response to medical regimes. The approaches presented here have the power to highlight mutations of clinical relevance in any gene of interest, thus to complement the arsenal of classic genetic screening tools.
2018
Cohen-Goldental, S. ; Biton, I. ; Zemach, H. ; Many, Y. ; Tonutti, P. ; Kerem, Z. ; Ben-Ari, G. Fruitlet abscission in olive (Olea europaea L.). In Acta Horticulturae; Acta Horticulturae; International Society for Horticultural Science (ISHS), Leuven, Belgium, 2018; pp. 215 - 220. Publisher's Version
Dag, A. ; Erel, R. ; Kerem, Z. ; Ben-Gal, A. ; Stern, N. ; Bustan, A. ; Zipori, I. ; Yermiyahu, U. Effect of nitrogen availability on olive oil quality. In Acta Horticulturae; Acta Horticulturae; International Society for Horticultural Science (ISHS), Leuven, Belgium, 2018; pp. 465 - 470. Publisher's Version
van-Oss, R. P. ; Gopher, A. ; Kerem, Z. ; Peleg, Z. ; Lev-Yadun, S. ; Sherman, A. ; Zhang, H. - B. ; Vandemark, G. ; Coyne, C. J. ; Reany, O. ; et al. Independent selection for seed free tryptophan content and vernalization response in chickpea domestication. Plant Breeding 2018, 137, 290-300. Publisher's VersionAbstract
Abstract Chickpea shows a distinct domestication trajectory vis-a-vis pod dehiscence and growth cycle mediated by vernalization insensitivity compared with its companion Near Eastern legumes. Our objectives were: (i) to map the quantitative trait loci (QTLs) associated with vernalization response and seed free tryptophan in domesticated × wild chickpea progeny and (ii) estimate the genetic correlation between vernalization response and free tryptophan content. A domesticated × wild chickpea cross was used to document phenotypic segregation in both traits and to construct a skeletal genetic map for QTL detection. A number of vernalization response and seed free tryptophan content QTLs were documented in both F2 and F3 generations. No significant genetic correlation between these two traits was observed. Epistatic relationship between two free tryptophan loci was documented. It is evident that selection for high seed tryptophan is easier to accomplish relative to selection for vernalization insensitivity. This suggests that the two traits were selected independently in antiquity, thereby corroborating earlier claims for conscious selection processes associated with chickpea domestication.
2017
Barazani, O. ; Waitz, Y. ; Tugendhaft, Y. ; Dorman, M. ; Dag, A. ; Hamidat, M. ; Hijawi, T. ; Kerem, Z. ; Westberg, E. ; Kadereit, J. W. Testing the potential significance of different scion/rootstock genotype combinations on the ecology of old cultivated olive trees in the southeast Mediterranean area. 2017, 17, 3. Publisher's VersionAbstract
A previous multi-locus lineage (MLL) analysis of SSR-microsatellite data of old olive trees in the southeast Mediterranean area had shown the predominance of the Souri cultivar (MLL1) among grafted trees. The MLL analysis had also identified an MLL (MLL7) that was more common among rootstocks than other MLLs. We here present a comparison of the MLL combinations MLL1 (scion)/MLL7 (rootstock) and MLL1/MLL1 in order to investigate the possible influence of rootstock on scion phenotype.