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Home > Press > Nanotechnology delivery system offers new approach to skin disease therapies: Hebrew University formula that activates the body's natural defense against free radicals could control a variety of skin pathologies and disorders Abstract: Researchers at The Hebrew University of Jerusalem have developed a nanotechnology-based delivery system containing a protective cellular pathway inducer that activates the body's natural defense against free radicals efficiently, a development that could control a variety of skin pathologies and disorders. The human skin is constantly exposed to various pollutants, UV rays, radiation and other stressors that exist in our day-to-day environment. When they filter into the body they can create Reactive Oxygen Species (ROS) - oxygen molecules known as Free Radicals, which are able to damage and destroy cells, including lipids, proteins and DNA. In the skin - the largest organ of the body - an excess of ROS can lead to various skin conditions, including inflammatory diseases, pigmenting disorders, wrinkles and some types of skin cancer, and can also affect internal organs. This damage is known as Oxidative Stress. The body is naturally equipped with defense mechanisms to counter oxidative stress. It has anti-oxidants and, more importantly, anti-oxidant enzymes that attack the ROS before they cause damage. In a review article published in the journal Cosmetics, a PhD student from The Hebrew University of Jerusalem, working in collaboration with researchers at the Technion - Israel Institute of Technology, suggested an innovative way to invigorate the body to produce antioxidant enzymes, while maintaining skin cell redox balance - a gentle equilibrium between Reactive Oxygen Species and their detoxification. "The approach of using the body's own defense system is very effective. We showed that activation of the body's defense system with the aid of a unique delivery system is feasible, and may leverage dermal cure," said Hebrew University researcher Maya Ben-Yehuda Greenwald. Ben-Yehuda Greenwald showed that applying nano-size droplets of microemulsion liquids containing a cellular protective pathway inducer into the skin activates the natural skin defense systems. "Currently, there are many scientific studies supporting the activation of the body's defense mechanisms. However, none of these studies has demonstrated the use of a nanotechnology-based delivery system to do so," Ben-Yehuda Greenwald said. Production of antioxidant enzymes in the body is signaled in the DNA by activation of Nrf2 - a powerful protein that exists in every cell in our body. This Nrf2 cellular-protective signaling pathway is a major intersection of many other signaling pathways affecting each other and determining cell functionality and fate. Nrf2 is capable of coordinating the cellular response to internal as well as external stressors by tight regulation of phase-II protective enzymes, such as the antioxidant enzymes. Ben-Yehuda Greenwald has also discovered a new family of compounds capable of activating the Nrf2 pathway. Moreover, by incorporating them into the unique delivery system she has developed, she managed to efficiently stimulate the activation of the Nrf2 pathway and mimic the activity of the body's' natural way of coping with a variety of stress conditions. "The formula we have created could be used in topical medication for treating skin conditions. Our formula could be used both as preventive means and for treatment of various skin conditions, such as infections, over-exposure to UV irradiation, inflammatory conditions, and also internal disease," she said. While the researchers focused on the skin, the formulation could prove to be effective in enhancing the body's natural protection against the damaging effects of ROS in other parts of the body, such as inflammation in cardiovascular diseases, heart attack, cancer, multiple sclerosis and Alzheimer's. ### Ben-Yehuda Greenwald integrated several fields of research into her work and was guided by experts in their fields - Prof. Roni Kohen, the Director of the School of Pharmacy, The Institute of Drug Research in the Hebrew University's Faculty of Medicine; Prof. Shmuel Ben-Sasson from the Department of Developmental Biology and Cancer Research at The Institute for Medical Research Israel-Canada in the Hebrew University's Faculty of Medicine; and Prof. Havazelet Bianco-Peled from the Department of Chemical Engineering at the Technion-Israel Institute of Technology. She conducted her study at the David and Ines Myers Skin Research Laboratory at The Institute for Drug Research in the School of Pharmacy at The Hebrew University's Faculty of Medicine. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


Yair R.,The Hebrew University | Uni Z.,The Hebrew University
Poultry Science | Year: 2011

Although embryo and chicken growth anddevelopment rely on mineral nutrition, information onmineral levels in the egg compartments during incubationis limited. Accordingly, we examined P, Ca, Fe, Zn,Cu, and Mn levels in the yolk of breeder eggs duringincubation and the effect of embryonic mineral (withspecific nutrients) enrichment on yolk mineral levelsand consumption. First, fertile eggs were examined onday of setting (DOS), embryonic day (E) 11, E13, E15,E17, E19, E20, and day of hatch (DOH) for the mineralcontent in the yolk (and albumen on DOS) by inductivelycoupled plasma atomic emission spectroscopy.Results showed that on DOS, the yolk is the majororigin for Mn, P, Fe, Ca, Cu, and Zn. Interestingly, P,Fe, Zn, Cu, and Mn were mostly consumed from theyolk until E17, after which their consumption was verylow. Consumption of P was constant until E17 and thendecreased until E20. Consumption of Fe, Zn, Cu, andMn was medium to mild until E11, increased betweenE11 and E17, and minimal between E17 and DOH.Enrichment treatment, where fertile eggs were dividedinto 2 groups [nonenriched (control) and enriched (withminerals, vitamins, and carbohydrates on E17 usingthe in ovo feeding method)] showed that the enrichedgroup had higher Fe, Zn, Cu, and Mn levels than thenonenriched group and exhibited higher consumptionof Fe, Zn, and Mn between E20 and DOH. Analysis ofthe shell mineral composition along incubation showedthat the shell released low amounts of P, Fe, and Mn incomparison with the yolk mineral content. Therefore,we concluded that the shell is a minor source of theseminerals. Studying the mineral resources and consumptionof embryos can lead to a better understanding ofthe mineral limitations of embryos during incubation.Additionally, because minerals are important for thedevelopment of the embryo, the higher mineral levelsand consumption observed in the enriched group mayaffect the development of critical organs, such as the skeletal system. © 2011 Poultry Science Association Inc.


Environmental stress-induced alterations in oocyte mitochondria are suggested to deleteriously affect developmental competence of the ovarian pool of oocytes. We examined the association between seasonal effects on oocyte developmental competence and mitochondrial distribution, polarization, mitochondrial DNA (mtDNA) content, and RNA expression, and whether the incorporation of coenzyme Q10 (CoQ10) might improve these effects. Bovine oocytes were collected during the summer (June-August), fall (September-November), and winter (December-May), matured in vitro with or without 50 lM CoQ10, fertilized, and cultured for 8 days. The proportion of developed blastocysts was highest in the winter, intermediate in the fall, and lowest in the summer. Matured oocytes were classified into categories I-IV according to their mitochondrial distribution pattern (MitoTracker green). The proportion of highand low-polarized mitochondria (JC-1 assay) differed between oocyte categories but was not affected by season. On the other hand, oocyte distribution into categories differed between seasons and was affected by CoQ10, with an increased proportion of category I oocytes in the fall. Oocyte mtDNA did not differ between seasons, but expression of mitochondrionassociated genes involved in the respiratory chain (ND2, SDHD, CYTB, COXII, ATP5B, and TFAM) did. Coenzyme Q10 increased the expression of CYTB, COXII, and ATP5B and the proportions of blastocysts developed in the fall. In summary, season-induced alterations in mitochondrial functions might explain, in part, the reduced oocyte developmental competence. It seems that in the fall, under modest harm, CoQ10 incorporation can alleviate these deleterious effects somewhat. © 2012 by the Society for the Study of Reproduction, Inc.


Yadgary L.,The Hebrew University | Uni Z.,The Hebrew University
Poultry Science | Year: 2012

Glycogen and glucose concentrations (mg/g of tissue) and amounts (mg) were determined in the yolks of fertile eggs on the day of set and in the yolk sac (YS) and liver of broiler chick embryos between 11 and 21 embryonic days of age (E). On the day of set, the yolk contained 50 mg of glucose (0.31% of yolk) but did not contain glycogen. During incubation, the amount of glucose in the YS increased from 20 mg on E11 to 60 mg on E19. A parallel increase in YS and liver glycogen concentrations (mg/g) during the last week of incubation implied a similar capacity for glycogen synthesis per gram of tissue. However, due to its larger size, the YS capacity for glycogen storage far exceeded that of the liver, which stored less than 12 mg of glycogen up to E19, as compared with more than 200 mg in the YS. Between E19 and 21, liver and YS glycogen amounts decreased by 10 mg and 100 mg, respectively. These results indicated that the YS is a glycogenic and perhaps gluconeogenic organ. We therefore evaluated the gene expression of glycogen synthase and glycogen phosphorylase as well as gluconeogenic enzymes (fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose 6-phosphatase) in the YS membrane and liver by real-time reverse-transcription PCR. Although the YS membrane and liver displayed different patterns of mRNA abundance, the high abundance of fructose 1,6-bisphosphatase mRNA in the YS membrane between E11 and 15, and the expression of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, supported the postulated gluconeogenic abilities of the YS membrane and indicated its role in providing glucose to the embryo. Thus, glucose is probably synthesized in the YS, stored in the form of glycogen, and toward hatch, the YS may have the potential to transfer 10 times more glycogen-derived glucose to the embryo as compared with the liver. As such, the YS may play a major role in the synthesis and storage of glucose and its supply to the chick embryo toward hatch. © 2012 Poultry Science Association Inc.


Weisburd D.,George Mason University | Weisburd D.,The Hebrew University
Criminology | Year: 2015

According to Laub (2004), criminology has a developmental life course with specific turning points that allow for innovations in how we understand and respond to crime. I argue that criminology should take another turn in direction, focusing on microgeographic hot spots. By examining articles published in Criminology, I show that only marginal attention has been paid to this area of study to date-often termed the criminology of place. I illustrate the potential utility of a turning point by examining the law of crime concentration at place, which states that for a defined measure of crime at a specific microgeographic unit, the concentration of crime will fall within a narrow bandwidth of percentages for a defined cumulative proportion of crime. By providing the first cross-city comparison of crime concentration using a common geographic unit, the same crime type, and examining a general crime measure, I find strong support for a law of crime concentration. I also show that crime concentration stays within a narrow bandwidth across time, despite strong volatility in crime incidents. By drawing from these findings, I identify several key research questions for future study. In conclusion, I argue that a focus on the criminology of place provides significant opportunity for young scholars and has great promise for advancing criminology as a science. © 2015 American Society of Criminology.


Levit A.,The Hebrew University
Methods in molecular biology (Clifton, N.J.) | Year: 2012

G protein-coupled receptors (GPCRs) are important mediators of cell signaling and a major family of drug targets. Despite recent breakthroughs, experimental elucidation of GPCR structures remains a formidable challenge. Homology modeling of 3D structures of GPCRs provides a practical tool for elucidating the structural determinants governing the interactions of these important receptors with their ligands. The working model of the binding site can then be used for virtual screening of additional ligands that may fit this site, for determining and comparing specificity profiles of related receptors, and for structure-based design of agonists and antagonists. The current review presents the protocol and enumerates the steps for modeling and validating the residues involved in ligand binding. The main stages include (a) modeling the receptor structure using an automated fragment-based approach, (b) predicting potential binding pockets, (c) docking known binders, (d) analyzing predicted interactions and comparing with positions that have been shown to bind ligands in other receptors, (e) validating the structural model by mutagenesis.


Yadgary L.,The Hebrew University | Wong E.A.,Virginia Polytechnic Institute and State University | Uni Z.,The Hebrew University
BMC Genomics | Year: 2014

Background: The yolk sac (YS) is an extra-embryonic tissue that surrounds the yolk and absorbs, digests and transports nutrients during incubation of the avian embryo as well as during early term mammalian embryonic development. Understanding YS functions and development may enhance the efficient transfer of nutrients and optimize embryo development. To identify temporal large-scale patterns of gene expression and gain insights into processes and mechanisms in the YS, we performed a transcriptome study of the YS of chick embryos on embryonic days (E) E13, E15, E17, E19, and E21 (hatch). Results: 3547 genes exhibited a significantly changed expression across days. Clustering and functional annotation of these genes as well as histological sectioning of the YS revealed that we monitored two cell types: the epithelial cells and the erythropoietic cells of the YS. We observed a significant up-regulation of epithelial genes involved in lipid transport and metabolism between E13 and E19. YS epithelial cells expressed a vast array of lipoprotein receptors and fatty acid transporters. Several lysosomal genes (CTSA, PSAP, NPC2) and apolipoproteins genes (apoA1, A2, B, C3) were among the highest expressed, reflecting the intensive digestion and re-synthesis of lipoproteins in YS epithelial cells. Genes associated with cytoskeletal structure were down-regulated between E17 and E21 supporting histological evidence of a degradation of YS epithelial cells towards hatch. Expression patterns of hemoglobin synthesis genes indicated a high erythropoietic capacity of the YS between E13 and E15, which decreased towards hatch. YS histological sections confirmed these results. We also observed that YS epithelial cells expressed high levels of genes coding for plasma carrier proteins (ALB, AFP, LTF, TTR), normally produced by the liver. Conclusions: Here we expand current knowledge on developmental, nutritional and molecular processes in the YS. We demonstrate that in the final week of chick embryonic development, the YS plays different roles to support or replace the functions of several organs that have not yet reached their full functional capacity. The YS has a similar functional role as the intestine in digestion and transport of nutrients, the liver in producing plasma carrier proteins and coagulation factors, and the bone marrow in synthesis of blood cells. © 2014 Yadgary et al.


Challa T.D.,The Hebrew University | Rais Y.,The Hebrew University | Ornan E.M.,The Hebrew University
Molecular and Cellular Endocrinology | Year: 2010

Adiponectin, an adipose-secreted adipocytokine, exhibits various metabolic functions but has no known effect on bone development through the growth plate and specifically, in chondrocytes. Using the mouse ATDC5 cell line, a widely used in vitro model of chondrogenesis, we demonstrated the expression of adiponectin and its receptors during chondrogenic differentiation. Adiponectin at 0.5. μg/ml increased chondrocyte proliferation, proteoglycan synthesis and matrix mineralization, as reflected by upregulation of the expression of type II collagen, aggrecan, Runx2 and type X collagen, and of alkaline phosphatase activity. Quantitative RT-PCR and gelatin zymography showed a significant increase in the matrix metalloproteinase MMP9's expression and activity following adiponectin treatment. We therefore concluded that adiponectin can directly stimulate chondrocyte proliferation and differentiation. To evaluate the underlying mechanisms, we examined the effect of adiponectin on the expression of chondrogenic signaling molecules: Ihh, PTHrP, Ptc1, FGF18, BMP7, IGF1 and p21 were all upregulated while FGF9 was downregulated. This study reveals novel and direct activity of adiponectin in chondrocytes, suggesting its positive effects on bone development. © 2010 Elsevier Ireland Ltd.


Dayan E.,Hebrew University of Jerusalem | Bar-Hillel M.,The Hebrew University
Judgment and Decision Making | Year: 2011

"Very small but cumulated decreases in food intake may be sufficient to have significant effects, even erasing obesity over a period of years" (Rozin et al., 2011). In two studies, one a lab study and the other a real-world study, we examine the effect of manipulating the position of different foods on a restaurant menu. Items placed at the beginning or the end of the list of their category options were up to twice as popular as when they were placed in the center of the list. Given this effect, placing healthier menu items at the top or bottom of item lists and less healthy ones in their center (e.g., sugared drinks vs. calorie-free drinks) should result in some increase in favor of healthier food choices.


All the Plutonium used on Earth is artificially produced in nuclear reactors. Still, it turns out that it is also produced in nature. "The origin of heavy elements produced in nature through rapid neutron capture ('r-process') by seed nuclei is one of the current nucleosynthesis mysteries," Dr. Kenta Hotokezaka, Prof. Tsvi Piran and Prof. Michael Paul from the Racah Institute of Physics at the Hebrew University of Jerusalem said in their letter. Plutonium is a radioactive element. Its longest-lived isotope is plutonium-244 with a lifetime of 120 million years. Detection of plutonium-244 in nature would imply that the element was synthesized in astrophysical phenomena not so long ago (at least in Galactic time scales) and hence its origin cannot be too far from us. Several years ago it was discovered that the early Solar system contained a significant amount of plutonium-244. Considering its short-lived cycle, plutonium-244 that existed over four billion years ago when Earth formed has long since decayed but its daughter elements have been detected. But recent measurements of the deposition of plutonium-244, including analysis of Galactic debris that fell to Earth and settled in deep sea, suggest that only very small amount of plutonium has reached Earth from outer space over the recent 100 million years. This is in striking contradiction to its presence at the time when the Solar system was formed, and that is why the Galactic radioactive plutonium remained a puzzle. The Hebrew University team of scientists have shown that these contradicting observations can be reconciled if the source of radioactive plutonium (as well as other rare elements, such as gold and uranium) is in mergers of binary neutron stars. These mergers are extremely rare events but are expected to produce large amounts of heavy elements. The model implies that such a merger took place accidentally in the vicinity of our Solar System within less than a hundred million years before it was born. This has led to the relatively large amount of plutonium-244 observed in the early Solar system. On the other hand, the relatively small amount of plutonium-244 reaching Earth from interstellar space today is simply accounted for by the rarity of these events. Such an event hasn't occurred in the last 100 million years in the vicinity of our Solar system. Explore further: Plutonium tricks cells by 'pretending' to be iron More information: Kenta Hotokezaka et al. Short-lived 244Pu points to compact binary mergers as sites for heavy r-process nucleosynthesis, Nature Physics (2015). DOI: 10.1038/nphys3574

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