Qiryat Shemona, Israel
Qiryat Shemona, Israel

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PubMed | Ben - Gurion University of the Negev, Migal Galilee Research Center, Tel Aviv University, Harvard University and 2 more.
Type: Journal Article | Journal: The New phytologist | Year: 2016

Plants have two kinds of fructokinases (FRKs) that catalyze the key step of fructose phosphorylation, cytosolic and plastidic. The major cytosolic tomato FRK, SlFRK2, is essential for the development of xylem vessels. In order to study the role of SlFRK3, which encodes the only plastidic FRK, we generated transgenic tomato (Solanum lycopersicon) plants with RNAi suppression of SlFRK3 as well as plants expressing beta-glucoronidase (GUS) under the SlFRK3 promoter. GUS staining indicated SlFRK3 expression in vascular tissues of the leaves and stems, including cambium, differentiating xylem, young xylem fibers and phloem companion cells. Suppression of SlFRK3 reduced the stem xylem area, stem and root water conductance, and whole-plant transpiration, with minor effects on plant development. However, suppression of SlFRK3 accompanied by partial suppression of SlFRK2 induced significant growth-inhibition effects, including the wilting of mature leaves. Grafting experiments revealed that these growth effects are imposed primarily by the leaves, whose petioles had unlignified, thin-walled xylem fibers with collapsed parenchyma cells around the vessels. A cross between the SlFRK2-antisense and SlFRK3-RNAi lines exhibited similar wilting and anatomical effects, confirming that these effects are the result of the combined suppression of SlFRK3 and SlFRK2. These results demonstrate a role of the plastidic SlFRK3 in xylem development and hydraulic conductance.


Alexander K.A.,Scottish Association for Marine Science | Angel D.,Haifa University | Freeman S.,Migal Galilee Research Center | Israel D.,Migal Galilee Research Center | And 8 more authors.
Environmental Science and Policy | Year: 2016

Research into stakeholder perceptions of conventional aquaculture has focused upon issues such as risk, impact on other users of marine space, and the factors influencing consumers. However, some of these issues may become redundant with new aquaculture practices such as Integrated Multi-trophic Aquaculture (IMTA). For practices such as IMTA to realise their potential they must be socially acceptable and this may depend on satisfying key stakeholders. This study used in-depth interviews to identify potential concerns of stakeholders as well as perceived benefits in relation to the development of IMTA to a commercial level of production. A total of 44 interviews were conducted across 12 stakeholder groups in six countries: Cyprus, Ireland, Israel, Italy, Norway and Scotland. Levels of awareness and understanding of IMTA were mixed across stakeholder groups and across countries. Concerns were raised including: spatial location issues, food safety and disease. Perceived benefits of IMTA included: waste utilisation, minimisation of impacts to the benthos and the filtering of sea lice larvae. Also recognised as important was the creation of new income streams. The results showed that some issues/benefits were more important in certain countries. Risks to the environment, risks arising from governance and risks to the industry itself were raised, but stakeholders felt that these sources of risk could be addressed by research studies, education and changes to legislation. Stakeholders also believed that IMTA could contribute to improving the image of the aquaculture industry. For IMTA to successfully move forward from pilot scale to commercial scale development, it is imperative that the issues raised in this study form priorities for reform and action. © 2015 Elsevier Ltd.


Freeman S.,Migal Galilee Research Center | Freeman S.,Hebrew University of Jerusalem | Kaufman-Shriqui V.,Hebrew University of Jerusalem | Kaufman-Shriqui V.,Ben - Gurion University of the Negev | And 5 more authors.
Food and Chemical Toxicology | Year: 2016

The presence of pesticides in the Israeli food supply is well documented but little is known about the risks posed by children's diets for potential exposures. We investigated potential exposures to food-borne pesticides in a sample of 301 urban Israeli children (2008-10). Data from a food frequency questionnaire, 24 hour food recall, and Israel's national pesticide monitoring program were used to estimate uptake factors for 26 compounds in 27 fruits and vegetables. A pilot risk assessment was performed and the findings were compared with the Israel Ministry of Health's 2012 pesticide risk assessment for the general population. The surveyed children had higher potential exposures than the general population for over one third of the compounds, and uptake factors exceeded the Acceptable Daily Intake in ten compounds. Methamidophos, exceeded the ADI at the 25th percentile and fenamiphos, iprodione, and oxydemethon methyl, exceeded the ADI at the 50 percentile. ADIs for several compounds were exceeded even though the residues detected were below the statutory limit. Improved monitoring, enforcement, and revision of the Maximum Residue Limit for certain food/pesticide pairs are indicated as is the need to incorporate data on children's actual food consumption in national risk assessments. © 2015 Elsevier Ltd.


Gal M.,Migal Galilee Research Center | Bloch I.,Migal Galilee Research Center | Shechter N.,Migal Galilee Research Center | Romanenko O.,Migal Galilee Research Center | Shir O.M.,Migal Galilee Research Center
Combinatorial Chemistry and High Throughput Screening | Year: 2016

Protein-protein interactions (PPI) play a critical role in regulating many cellular processes. Finding novel PPI inhibitors that interfere with specific binding of two proteins is considered a great challenge, mainly due to the complexity involved in characterizing multi-molecular systems and limited understanding of the physical principles governing PPIs. Here we show that the combination of virtual screening techniques, which are capable of filtering a large library of potential small molecule inhibitors, and a unique secondary screening by isothermal titration calorimetry, a label-free method capable of observing direct interactions, is an efficient tool for finding such an inhibitor. In this study we applied this strategy in a search for a small molecule capable of interfering with the interaction of the tumor-suppressor p53 and the E3-ligase MDM2. We virtually screened a library of 15 million small molecules that were filtered to a final set of 80 virtual hits. Our in vitro experimental assay, designed to validate the activity of mixtures of compounds by isothermal titration calorimetry, was used to identify an active molecule against MDM2. At the end of the process the small molecule (4S,7R)-4-(4-chlorophenyl)-5-hydroxy-2,7-dimethyl-N-(6-methylpyridin-2-yl)-4,6,7,8 tetrahydrIoquinoline-3-carboxamide was found to bind MDM2 with a dissociation constant of ~2 μM. Following the identification of this single bioactive compound, spectroscopic measurements were used to further characterize the interaction of the small molecule with the target protein. 2D NMR spectroscopy was used to map the binding region of the small molecule, and fluorescence polarization measurement confirmed that it indeed competes with p53. © 2016 Bentham Science Publishers.


PubMed | Migal Galilee Research Center
Type: Journal Article | Journal: Combinatorial chemistry & high throughput screening | Year: 2016

Protein-protein interactions (PPI) play a critical role in regulating many cellular processes. Finding novel PPI inhibitors that interfere with specific binding of two proteins is considered a great challenge, mainly due to the complexity involved in characterizing multi-molecular systems and limited understanding of the physical principles governing PPIs. Here we show that the combination of virtual screening techniques, which are capable of filtering a large library of potential small molecule inhibitors, and a unique secondary screening by isothermal titration calorimetry, a label-free method capable of observing direct interactions, is an efficient tool for finding such an inhibitor. In this study we applied this strategy in a search for a small molecule capable of interfering with the interaction of the tumor-suppressor p53 and the E3-ligase MDM2. We virtually screened a library of 15 million small molecules that were filtered to a final set of 80 virtual hits. Our in vitro experimental assay, designed to validate the activity of mixtures of compounds by isothermal titration calorimetry, was used to identify an active molecule against MDM2. At the end of the process the small molecule (4S,7R)-4-(4-chlorophenyl)-5-hydroxy-2,7-dimethyl-N-(6-methylpyridin-2-yl)-4,6,7,8 tetrahydrIoquinoline-3-carboxamide was found to bind MDM2 with a dissociation constant of ~2 M. Following the identification of this single bioactive compound, spectroscopic measurements were used to further characterize the interaction of the small molecule with the target protein. 2D NMR spectroscopy was used to map the binding region of the small molecule, and fluorescence polarization measurement confirmed that it indeed competes with p53.

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