Leibovitz S, Y, Haviv , Y, Sharav , G, Almoznino , D, Aframian , ו U., Zilberman . 2017.
“Pediatric Sleep-Disordered Breathing: Role Of The Dentist”. Quintessence Int., Pp. 48(8):639-645. .
Publisher's Version Hagay Kohay, Sarisozen, Can , Sawant, Rupa , Jhaveri, Aditi , Torchilin, Vladimir P, ו Mishael, Yael G.. 2017.
“Peg-Pe/Clay Composite Carriers For Doxorubicin: Effect Of Composite Structure On Release, Cell Interaction And Cytotoxicity”. Acta Biomater, 55, Pp. 443-454. doi:10.1016/j.actbio.2017.04.008.
תקציר A novel drug delivery system for doxorubicin (DOX), based on organic-inorganic composites was developed. DOX was incorporated in micelles (M-DOX) of polyethylene glycol-phosphatidylethanolamine (PEG-PE) which in turn were adsorbed by the clay, montmorillonite (MMT). The nano-structures of the PEG-PE/MMT composites of LOW and HIGH polymer loadings were characterized by XRD, TGA, FTIR, size (DLS) and zeta measurements. These measurements suggest that for the LOW composite a single layer of polymer intercalates in the clay platelets and the polymer only partially covers the external surface, while for the HIGH composite two layers of polymer intercalate and a bilayer may form on the external surface. These nanostructures have a direct effect on formulation stability and on the rate of DOX release. The release rate was reversely correlated with the degree of DOX interaction with the clay and followed the sequence: M-DOX>HIGH formulation>LOW formulation>DOX/MMT. Despite the slower release from the HIGH formulation, its cytotoxicity effect on sensitive cells was as high as the "free" DOX. Surprisingly, the LOW formulation, with the slowest release, demonstrated the highest cytotoxicity in the case of Adriamycin (ADR) resistant cells. Confocal microscopy images and association tests provided an insight into the contribution of formulation-cell interactions vs. the contribution of DOX release rate. Internalization of the formulations was suggested as a mechanism that increases DOX efficiency, particularly in the ADR resistant cell line. The employment of organic-inorganic hybrid materials as drug delivery systems, has not reached its full potential, however, its functionality as an efficient tunable release system was demonstrated. STATEMENT OF SIGNIFICANCE: DOX PEG-PE/clay formulations were design as an efficient drug delivery system. The main aim was to develop PEG-PE/clay formulations of different structures based on various PEG-PE/clay ratios in order to achieve tunable release rates, to control the external surface characteristics and formulation stability. The formulations showed significantly higher toxicity in comparison to "free" DOX, explained by formulation internalization. For each cell line tested, sensitive and ADR resistant, a different formulation structure was found most efficient. The potential of PEG-PE/clay-DOX formulations to improve DOX administration efficacy was demonstrated and should be further explored and implemented for other cancer drugs and cells.
We have recently reported the covalent inhibition of HIV-1 integrase by an N-terminal succinimide-modified lens epithelium-derived growth factor (361-370) peptide. We also showed that this peptide is proteolytically stable. Here, we show that this inhibitor is stored as fibrils that serve as a stock for the inhibitory monomers. The fibrils increase the local concentration of the peptide at the target protein. When the monomers bind integrase, the equilibrium between the fibrils and their monomers shifts towards the formation of peptide monomers. The combination of fibril formation and subsequent proteolytic stability of the peptide may bring to new strategy for developing therapeutic agents.
Koushik Chandra, Das, Priyadip , Metanis, Norman , Friedler, Assaf , ו Reches, Meital . 2017.
“Peptide Fibrils As Monomer Storage Of The Covalent Hiv-1 Integrase Inhibitor”. Journal Of Peptide Science, 23, 2, Pp. 117-121.
תקציר Joseph Tam, Szanda, Gergő , Drori, Adi , Liu, Ziyi , Cinar, Resat , Kashiwaya, Yoshihiro , Reitman, Marc L, ו Kunos, George . 2017.
“Peripheral Cannabinoid-1 Receptor Blockade Restores Hypothalamic Leptin Signaling.”. Molecular Metabolism, 6, 10, Pp. 1113–1125. doi:10.1016/j.molmet.2017.06.010.
תקציר OBJECTIVE: In visceral obesity, an overactive endocannabinoid/CB(1) receptor (CB(1)R) system promotes increased caloric intake and decreases energy expenditure, which are mitigated by global or peripheral CB(1)R blockade. In mice with diet-induced obesity (DIO), inhibition of food intake by the peripherally restricted CB(1)R antagonist JD5037 could be attributed to endogenous leptin due to the rapid reversal of hyperleptinemia that maintains leptin resistance, but the signaling pathway engaged by leptin has remained to be determined. METHODS: We analyzed the hypothalamic circuitry targeted by leptin following chronic treatment of DIO mice with JD5037. RESULTS: Leptin treatment or an increase in endogenous leptin following fasting/refeeding induced STAT3 phosphorylation in neurons in the arcuate nucleus (ARC) in lean and JD5037-treated DIO mice, but not in vehicle-treated DIO animals. Co-localization of pSTAT3 in leptin-treated mice was significantly less common with NPY(+) than with POMC(+) ARC neurons. The hypophagic effect of JD5037 was absent in melanocortin-4 receptor (MC4R) deficient obese mice or DIO mice treated with a MC4R antagonist, but was maintained in NPY(-/-) mice kept on a high-fat diet. CONCLUSIONS: Peripheral CB(1)R blockade in DIO restores sensitivity to endogenous leptin, which elicits hypophagia via the re-activation of melanocortin signaling in the ARC.
ABSTRACTMost floating aquatic plants have stomata on their upper leaf surfaces, and usually their stomata are permanently open. We previously identified 3 distinct crystallinity patterns in stomatal cell walls, with angiosperm kidney-shaped stomata having the highest crystallinity in the polar end walls as well as the adjacent polar regions of the guard cells. A numerical bio-mechanical model suggested that the high crystallinity areas are localized to regions where the highest stress is imposed. Here, stomatal cell wall crystallinity was examined in 4 floating plants from 2 different taxa: basal angiosperms from the ANITA grade and monocots. It appears that the non-functional stomata of floating plants display reduced crystallinity in the polar regions as compared with high crystallinity of the ventral (inner) walls. Thus their guard cells are both less flexible and less stress resistant. Our findings suggest that the pattern of cellulose crystallinity in stomata of floating plants from different families was altered as a consequence of similar evolutionary pressures.
Cancer and genomic instability are highly impacted by the deoxyribonucleic acid (DNA) replication program. Inaccuracies in DNA replication lead to the increased acquisition of mutations and structural variations. These inaccuracies mainly stem from loss of DNA fidelity due to replication stress or due to aberrations in the temporal organization of the replication process. Here we review the mechanisms and impact of these major sources of error to the replication program.
Sutharsan Govindarajan, Albocher, Nitsan , Szoke, Tamar , Nussbaum-Shochat, Anat , ו Amster-Choder, Orna . 2017.
“Phenotypic Heterogeneity In Sugar Utilization By E. Coli Is Generated By Stochastic Dispersal Of The General Pts Protein Ei From Polar Clusters”. Front. Microbiol., 8, Pp. 2695.
תקציר Although the list of proteins that localize to the bacterial cell poles is constantly growing, little is known about their temporal behavior. EI, a major protein of the phosphotransferase system (PTS) that regulates sugar uptake and metabolism in bacteria, was shown to form clusters at the Escherichia coli cell poles. We monitored the localization of EI clusters, as well as diffuse molecules, in space and time during the lifetime of E. coli cells. We show that EI distribution and cluster dynamics varies among cells in a population, and that the cluster speed inversely correlates with cluster size. In growing cells, EI is not assembled into clusters in almost 40% of the cells, and the clusters in most remaining cells dynamically relocate within the pole region or between the poles. In non-growing cells, the fraction of cells that contain EI clusters is significantly higher, and dispersal of these clusters is often observed shortly after exiting quiescence. Later, during growth, EI clusters stochastically re-form by assembly of pre-existing dispersed molecules at random time points. Using a fluorescent glucose analog, we found that EI function inversely correlates with clustering and with cluster size. Thus, activity is exerted by dispersed EI molecules, whereas the polar clusters serve as a reservoir of molecules ready to act when needed. Taken together our findings highlight the spatiotemporal distribution of EI as a novel layer of regulation that contributes to the population phenotypic heterogeneity with regard to sugar metabolism, seemingly conferring a survival benefit.
Alon Cna'ani, Shavit, Reut , Ravid, Jasmin , Aravena-Calvo, Javiera , Skaliter, Oded , Masci, Tania , ו Vainstein, Alexander . 2017.
“Phenylpropanoid Scent Compounds In Petunia X Hybrida Are Glycosylated And Accumulate In Vacuoles”. Frontiers In Plant Science, 8, Pp. 1898. doi:10.3389/fpls.2017.01898.
Publisher's Version תקציר Floral scent has been studied extensively in the model plant Petunia. However, little is known about the intracellular fate of scent compounds. Here, we characterize the glycosylation of phenylpropanoid scent compounds in Petunia x hybrida. This modification reduces scent compounds' volatility, reactivity, and autotoxicity while increasing their water-solubility. Gas chromatography–mass spectrometry (GC–MS) analyses revealed that flowers of petunia cultivars accumulate substantial amounts of glycosylated scent compounds and that their increasing level parallels flower development. In contrast to the pool of accumulated aglycones, which drops considerably at the beginning of the light period, the collective pool of glycosides starts to increase at that time and does not decrease thereafter. The glycoside pool is dynamic and is generated or catabolized during peak scent emission, as inferred from phenylalanine isotope-feeding experiments. Using several approaches, we show that phenylpropanoid scent compounds are stored as glycosides in the vacuoles of petal cells: ectopic expression of Aspergillus niger β-glucosidase-1 targeted to the vacuole resulted in decreased glycoside accumulation; GC–MS analysis of intact vacuoles isolated from petal protoplasts revealed the presence of glycosylated scent compounds. Accumulation of glycosides in the vacuoles seems to be a common mechanism for phenylpropanoid metabolites.
Doping of semiconductor nanocrystals is an emerging tool to control their properties and has recently received increased interest as the means to characterize the impurities and their effect on the electronic characteristics of the nanocrystal evolve. We present a temperature-dependent Raman scattering study of Cu-doped InAs nanocrystals observing changes in the relative scattering intensities of the different modes upon increased dopant concentrations. First, the longitudinal optical (LO) phonon overtone mode is suppressed, indicating weakening of the coupling strength related to the effect of screening by the free electrons. Second, the transverse optical (TO) mode is relatively enhanced compared to the LO mode, which is attributed to the appearance of a coupled phonon–plasmon mode analogous to observations for n-type doped bulk InAs. These signatures indicate that the Cu impurities serve as active dopants and occupy an impurity-related pseudo sub-band akin to the heavy doping limit.
Keren Harel-Dassa, Yedgar, Saul , Tropé, Claes G, Davidson, Ben , ו Reich, Reuven . 2017.
“Phospholipase D Messenger Rna Expression And Clinical Role In High-Grade Serous Carcinoma.”. Human Pathology, 62, Pp. 115–121. doi:10.1016/j.humpath.2016.12.023.
תקציר The objective of this study was to analyze the expression and clinical role of phospholipase D (PLD) in high-grade serous carcinoma (HGSC). PLD1 and PLD2 isoform expression was studied in 125 HGSC specimens (73 effusions, 28 ovarian tumors, 24 solid metastases) using quantitative real-time reverse-transcription polymerase chain reaction. Expression levels were analyzed for association with clinicopathological parameters, including chemoresponse, and survival. PLD1 and PLD2 isoforms were found in most specimens at all anatomic sites, and their levels were strongly positively related (P<.001 for effusions and solid lesions). PLD2 messenger RNA (mRNA) expression was significantly higher in effusions compared with both carcinomas in the ovary and solid metastases (P<.001). Higher levels of both isoforms were associated with higher CA 125 levels at diagnosis (P<.001), and higher PLD2 mRNA levels in effusions were associated with unfavorable response to chemotherapy (P=.021). Expression levels of the studied isoforms were unrelated to the levels of previously studied mRNAs that form part of the phospholipase A(2) pathway or to survival. The present study provides the first evidence of PLD expression in HGSC and suggests a role in mediating progression to effusions and chemoresistance in this cancer.
Voolstra O, E, Rhodes-Mordov , B, Katz , JP, Bartels , C, Oberegelsbacher , SK, Schotthofer , B, Yasin , H, Tzadok , A, Huber , ו B., Minke . 4/12/2017.
“The Phosphorylation State Of The Drosophila Trp Channel Modulates The Frequency Response To Oscillating Light In Vivo”. J Neurosci, (15), 37, Pp. 4213-4224 . .
Publisher's Version Adopting an interdisciplinary approach to the study of photoassimilate partitioning and source-sink relationhips, this work details the major aspects of source-sink physiology and metabolism, the integration of individual components and photoassimilate partitioning, and the whole plant source-sink relationships in 16 agriculturally important crops. The work examines in detail the components of carbon partitioning, such as ecology, photosynthesis, loading, transport and anatomy, and discusses the impact of genetic, environmental and agrotechnical factors on the parts of whole plant source-link physiology. © 1996 by Marcel Dekker, Inc. All Rights Reserved.
Yuval Ben-Shahar, Vinokurov, Kathy , de Paz-Simon, Héloïse , Gofer, Yosef , Leiter, Matan , Banin, Uri , ו Cohen, Yaron S. 2017.
“Photoelectrochemistry Of Colloidal Cu 2 O Nanocrystal Layers: The Role Of Interfacial Chemistry”. Journal Of Materials Chemistry A, 5, 42, Pp. 22255-22264. .
Publisher's Version תקציר 
Colloidal Cu2O nanocrystal layers on Au substrates are studied as photocathodes in the context of solar electrochemical water-splitting applications. The photoelectrochemical response of the nanocrystal layers in aqueous solutions under simulated solar light conditions depends strongly on the interfacial chemistry and its impact on the transport of the charge carriers across the Au/nanocrystals/liquid interfaces. The Cu2O nanocrystals are originally stabilized with octadecylamine ligands. While octadecylamine is an efficient capping ligand for the colloidal synthesis of highly uniform nanocrystals, its low conductivity impedes the charge transport across the Au/nanocrystals/liquid interfaces. The photoresponse of the nanocrystals can be enhanced by the replacement of the octadecylamine ligands with more conductive and hydrophilic molecules, such as 1,2-ethanedithiol and benzene-1,4-dithiol. The conductivity and hydrophilicity of the ligands were investigated and found to be important for the photo-induced charge separation and transport across the Au/nanocrystals/liquid interfaces and transfer to the liquid. Furthermore, the interfacial energetics of the Au/nanocrystals/liquid junction and the resulting photoresponse of the Cu2O nanocrystal photocathode can be optimized by rational design of the exchanging ligands with desired functionalities and dipoles at the specific interfaces. A comparison of the photoresponse of Cu2O nanocrystal layers to that of electrodeposited Cu2O layers shows that the former is, yet, lower, due to the apparent low conductivity of the ligands. However, the nanocrystal organic ligands impart high hydrophobicity, which prevents the contact of the aqueous solution with the nanocrystals and improves their stability against photocorrosion and reduction to Cu0, as confirmed by X-ray diffraction measurements.
