Biyoinformatik ve Genetik Bölümü Koleksiyonu
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Conference Object Citation Count: 0The Association of Gvhd With Hla Dr Alleles, Ifn-Gamma, Tgf-Beta, And Mbl2 Gene Polymorphism(Wiley, 2019) Oğuz, Rusdu; Çiftçi, Hayriye Şentürk; Gökçe, Muge; Öğret, Yeliz; Karadeniz, Sedat Tanju; Pehlivan, Sacide; Aydın, Filiz[Abstract Not Available]Article Citation Count: 5Calculating Level Densities of Heavy Nuclei by the Shell Model Monte Carlo Method(Academic Press Inc Elsevier Science, 2014) Alhassid, Yoram; Özen, Cem; Nakada, HitoshiThe microscopic calculation of nuclear level densities in the presence of correlations is a difficult many-body problem. The shell model Monte Carlo method provides a powerful technique to carry out such calculations using the framework of the configuration-interaction shell model in spaces that are many orders of magnitude larger than spaces that can be treated by conventional methods. We present recent applications of the method to the calculation of level densities and their collective enhancement factors in heavy nuclei. The calculated level densities are in close agreement with experimental data.Article Citation Count: 30Cis-cyclopropylamines as mechanism-based inhibitors of monoamine oxidases(Wiley-Blackwell, 2015) Yelekçi, Kemal; Yelekçi, Kemal; Borrello, Maria Teresa; Ganesan, A.; Semina, Elena; De Kimpe, Norbert; Mangelinckx, Sven; Ramsay, Rona R.Cyclopropylamines inhibitors of monoamine oxidases (MAO) and lysine-specific demethylase (LSD1) provide a useful structural scaffold for the design of mechanism-based inhibitors for treatment of depression and cancer. For new compounds with the less common cis relationship and with an alkoxy substituent at the 2-position of the cyclopropyl ring the apparent affinity determined from docking experiments revealed little difference between the enantiomers. Using the racemate kinetic parameters for the reversible and irreversible inhibition of MAO were determined. No inhibition of LSD1 was observed. For reversible inhibition most compounds gave high IC50 values with MAO A but sub-micromolar values with MAO B. After pre-incubation of the cyclopropylamine with the enzyme the inhibition was irreversible for both MAOA and MAOB and the activity was not restored by dilution. Spectral changes during inactivation of MAOA included bleaching at 456nm and an increased absorbance at 400nm consistent with flavin modification. These derivatives are MAOB-selective irreversible inhibitors that do not show inhibition of LSD1. The best inhibitor was cis-N-benzyl-2-methoxycyclopropylamine with an IC50 of 5nm for MAOB and 170nm for MAOA after 30min pre-incubation. This cis-cyclopropylamine is over 20-fold more effective than tranylcypromine so may be studied as a lead for selective inhibitors of MAOB that do not inhibit LSD1.Article Citation Count: 5Computational Analysis of a Zn-Bound Tris(imidazolyl) Calix[6]arene Aqua Complex: Toward Incorporating Second-Coordination Sphere Effects into Carbonic Anhydrase Biomimetics(Amer Chemical Soc, 2013) Eşsiz, Şebnem; Eşsiz, Şebnem; Wong, Sergio E.; Lau, Edmond Y.; Valdez, Carlos A.; Satcher, Joe H. Jr.; Aines, Roger D.; Lightstone, Felice C.Molecular dynamics simulations and quantum-mechanical calculations were performed to characterize a supra-molecular tris(imidazolyl) calix[6]arene Zn2+ aqua complex as a biomimetic model for the catalyzed hydration of carbon dioxide to bicarbonate H2O + CO2 -> H+ + HCO3-. On the basis of potential-of-mean-force (PMF) calculations stable conformations had distorted 3-fold symmetry and supported either one or zero encapsulated water molecules. The conformation with an encapsulated water molecule is calculated to be lower in free energy than the conformation with an empty cavity (Delta G = 1.2 kcal/mol) and is the calculated free-energy minimum in solution. CO2 molecule partitioning into the cavity is shown to be very facile proceeding with a barrier of 1.6 kcal/mol from a weak encounter complex which stabilizes the species by about 1.0 kcal/mol. The stabilization energy of CO2 is calculated to be larger than that of H2O (Delta Delta G = 1.4 kcal/mol) suggesting that the complex will preferentially encapsulate CO2 in solution. In contrast the PMF for a bicarbonate anion entering the cavity is calculated to be repulsive in all nonbonding regions of the cavity due to the diameter of the calix[6]arene walls. Geometry optimization of the Zn-bound hydroxide complex with an encapsulated CO2 molecule showed that multiple noncovalent interactions direct the reactants into optimal position for nucleophilic addition to occur. The calixarene complex is a structural mimic of the hydrophilic/hydrophobic divide in the enzyme providing a functional effect for CO2 addition in the catalytic cycle. The results show that Zn-binding calix[6]arene scaffolds can be potential synthetic biomimetics for CO2 hydration catalysis both in terms of preferentially encapsulating CO2 from solution and by spatially fixing the reactive species inside the cavity.Review Citation Count: 6Critical phenomenon during photoinitiated gelation at different temperatures: A Photo-DSC study(Elsevier Science, 2011) Dogruyol, Zekeriya; Arsu, Nergis; Dogruyol, Sevnur Keskin; Pekcan, ÖnderThe behaviour of photoinitiated radical polymerization of an 80 wt% epoxy diacrylate (EA) and 20 wt% tripropyleneglycoldiacrylate (TPGDA) mixture with 2-mercaptothioxanthone (TX-SH) photoinitiator was studied at different temperatures by using photo-differential scanning calorimetric (Photo-DSC) technique. All photopolymerization reactions were carried out under the same conditions. It was observed that all conversion curves during gelation at different temperatures present nice sigmoidal behaviour which suggests the application of the percolation model. Observations around the critical time called the glass transition point (t(g)) taken to reach the maximum rate of polymerization (Rp(max)) show that the gel fraction exponent (beta) obeyed the percolation model. The produced beta values were found to be around 0.50 predicting that the system under consideration belongs to the same universality class. However. Rp(max) and the final conversion (C(s)) values were found to increase when the temperature was increased up to a certain value. On the other hand t(g) values decreased and became saturated as the temperature was increased. (C) 2011 Elsevier B.V. All rights reserved.Article Citation Count: 44Crossover from Vibrational to Rotational Collectivity in Heavy Nuclei in the Shell-Model Monte Carlo Approach(Amer Physical Soc., 2013) Özen, Cem; Alhassid, Yoram; Nakada, HitoshiHeavy nuclei exhibit a crossover from vibrational to rotational collectivity as the number of neutrons or protons increases from shell closure towards midshell but the microscopic description of this crossover has been a major challenge. We apply the shell model Monte Carlo approach to families of even-even samarium and neodymium isotopes and identify a microscopic signature of the crossover from vibrational to rotational collectivity in the low-temperature behavior of < J(2)>(T) where J is the total spin and T is the temperature. This signature agrees well with its values extracted from experimental data. We also calculate the state densities of these nuclei and find them to be in very good agreement with experimental data. Finally we define a collective enhancement factor from the ratio of the total state density to the intrinsic state density as calculated in the finite-temperature Hartree-Fock-Bogoliubov approximation. The decay of this enhancement factor with excitation energy is found to correlate with the pairing and shape phase transitions in these nuclei. DOI: 10.1103/PhysRevLett.110.042502Conference Object Citation Count: 0Design and synthesis of novel 2-pyrazoline analogues and their hMAO inhibitory activities(Wiley-Blackwell, 2015) Yelekçi, Kemal; Evranos-Aksoz, Begum; Yabanoglu-Çiftçi, Samiye; Yelekçi, Kemal[Abstract Not Available]Correction Citation Count: 0Discovery of new azoles with potent activity against Candida spp. and Candida albicans biofilms through virtual screening(Elsevier, 2020) Eşsiz, Şebnem; Kart, Didem; Öztürk, Naile; Kaynak, F. Betül; Gencel, Melis; Taşkor, Gülce; Karakurt, Arzu; Saraç, Selma; Eşsiz, Şebnem; Dalkara, SevimSystemic candidiasis is a rampant bloodstream infection ofCandidaspp. andC. albicansis the majorpathogen isolated from infected humans. Azoles, the most common class of antifungals which sufferfrom increasing resistance, and especially intrinsically resistant non-albicans Candida(NAC) species, actby inhibiting fungal lanosterol 14a-demethylase (CYP51). In this study we identified a number of azolecompounds in 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol/ethanone oxime ester structurethrough virtual screening using consensus scoring approach, synthesized and tested them for theirantifungal properties. We reached several hits with potent activity against azole-susceptible and azole-resistantCandidaspp. as well as biofilms ofC. albicans.5i's minimum inhibitor concentration (MIC) was0.125mg/ml againstC. albicans, 0.5mg/ml againstC. kruseiand 1mg/ml against azole-resistantC. tropicalisisolate. Considering the MIC values offluconazole against these fungi (0.5, 32 and 512mg/ml, respec-tively),5iemerged as a highly potent derivative. The minimum biofilm inhibitor concentration (MBIC) of5c,5j, and5pwere 0.5mg/ml (and5iwas 2mg/ml) againstC. albicansbiofilms, lower than that ofamphotericin B (4mg/ml), afirst-line antifungal with antibiofilm activity. In addition, the active com-pounds showed neglectable toxicity to human monocytic cell line. We further analyzed the dockingposes of the active compounds inC. albicansCYP51 (CACYP51) homology model catalytic site andidentified molecular interactions in agreement with those of known azoles with fungal CYP51s andmutagenesis studies of CACYP51. We observed the stability of CACYP51 in complex with5iin moleculardynamics simulations.©2019 Elsevier Masson SAS. All rights reserved.1. IntroductionSystemic candidiasis is a major public health issue, especiallywith immune-suppressed cases reaching high mortality rates. Themembers of the genusCandidaare the most frequently recoveredfrom human fungal infection andCandida albicans, so far, is theleading pathogen identified in nosocomial candidiasis [1]. Inaddition to increasing drug-resistant strains ofC. albicans, emer-gence of non-albicans Candidaspp. (NAC) complicate the treatmentof mycoses [2].C. tropicalisis among the NACs that show reducedsusceptibility tofirst-line antifungals reportedly leading to break-through fungemia among high-risk patients [3,4]. Also,C. kruseiisknown to be intrinsically resistant to a number of azoles includingfluconazole [5]. One of the several mechanisms of therapy-resistance is formation of biofilms, which are complex microor-ganism colonies enclosed in an exopolysaccharide matrix on bioticand non-biotic surfaces. Persistent biofilms make fungi much lesssusceptible to antifungal drugs compared to their planktonic formsfor a number of reasons [6e8]. Therefore it is essential to design*Corresponding author. Hacettepe University Faculty of Pharmacy, Departmentof Pharmaceutical Chemistry, 06100, Sihhiye, Ankara, Turkey.E-mail addresses:suat.sari@hacettepe.edu.tr,suat1039@gmail.com(S. Sari).Contents lists available atScienceDirectEuropean Journal of Medicinal Chemistryjournal homepage:http://www.elsevier.com/locate/ejmechhttps://doi.org/10.1016/j.ejmech.2019.06.0830223-5234/©2019 Elsevier Masson SAS. All rights reserved.European Journal of Medicinal Chemistry 179 (2019) 634e648Article Citation Count: 81Electrical and optical percolations of polystyrene latex-multiwalled carbon nanotube composites(Academic Press Inc Elsevier Science, 2010) Kara, Selim; Arda, Ertan; Dolastir, Fahrettin; Pekcan, ÖnderElectrical conductivity and optical transmittance properties of polystyrene (PS)-multiwalled carbon nanotube (MWCNT) composite films were investigated. Composite films were prepared by mixing of various mass fractions of MWCNT in PS-water dispersions. After water evaporates powder composite films were annealed at 175 degrees C above the glass transition of PS for 20 min. Photon transmission and two point probe resistivity techniques were employed to determine the variations of the optical and the electrical properties of composites. Transmitted light intensity I(tr) and surface resistivity R(s) were monitored as a function of MWCNT mass fraction (M). It was observed that both the surface resistivity and the optical transparency were decreased by increasing the amount of MWCNT added to the polymeric system. Conductivity and optical results were interpreted according to the classical and site percolation theory respectively. The electrical (sigma) and the optical (op) percolation threshold values and critical exponents were calculated as M(sigma) = 1.8 wt.% M(op) = 0-0.13 wt.% and beta(sigma) = 2.25 beta(op) = 0.32 respectively. (C) 2010 Elsevier Inc. All rights reserved.Article Citation Count: 4The Electrochromic Performances of Single Phase VO2 Nanoparticled Films(Elsevier Science SA, 2016) Akkaya Arier, Ümit Özlem; Uysal, Bengü ÖzuğurIn the present work pure phase vanadium oxide VO2 nanoparticled films were synthesized using acetate based sol-gel precursors. The effect of the water: Vanadyl acetylacetonate ratio on electrochemical and structural properties of nanostructured vanadium oxide films was examined. The X-ray diffraction studies indicated that very strong crystallization of the VO2 monoclinic phase occurred for the as-deposited films at the annealing temperature of 500 degrees C. According to the atomic force microscopy and scanning electron microscopy measurements the size and morphology of the granular structured film depend on the water: Vanadyl acetylacetonate ratio. I-V curve spectra were used to compute several characteristics of the films coated on indium tin oxide substrates such as the optical density color efficiency and diffusion coefficient. Even though water: Vanadyl acetylacetonate ratio of 0.1 is expected to give the highest color efficiency value (33 cm(2)/C) higher diffusion coefficient (3.15 x 10(-12) cm(2)/s) is observed in the ratio of 0.01. As a result the correlation between the ratios and electrochromic properties of the films was established. (C) 2016 Elsevier B.V. All rights reserved.Conference Object Citation Count: 0Epitope Based Hla Matching By Using Antibody Reactivity With High Resolution Allele Typing And Hlamatchmaker Algorithm Based Software(Wiley, 2017) Yelekçi, Kemal; Akgül, Sebahat Usta; Çiftçi, Hayriye Şentürk; Öğret, Yeliz; Oğuz, Fatma; Yelekçi, Kemal; Aydın, Filiz[Abstract Not Available]Article Citation Count: 4Fluorescence quenching method for monitoring oxygen diffusion into PS/CNT composite films(Elsevier Science SA, 2013) Yargı, Önder; Uğur, Şaziye; Pekcan, ÖnderOxygen permeabilities of nanocomposite films consisting of multi wall carbon nanotubes (MWNT) and polystyrene (PS) were determined to investigate the oxygen diffusion depending on MWNT and temperature. A method which is based on quenching of an excited phosphorescent by oxygen was applied for the measurements. The composite films were prepared from mixtures of (MWNT) and surfactant-free pyrene (P)-labeled (PS) latexes of various compositions at room temperature. These films were then annealed at 170 degrees C which is well above the glass transition (T-g) temperature of polystyrene for 10 min. Diffusion experiments were performed for eight films with different MWNT content (0 1.5 3 5 10 15 25 and 40 wt%) to evaluate the effect of MWNT content on oxygen diffusion. Diffusion coefficients were found to increase from 1.1 x 10(-12) to 41 x 10(-12) cm(2) s(-1) with increasing MWNT content. On the other hand to examine the effect of temperature on oxygen diffusion diffusion measurements were performed over a temperature range of 24-70 degrees C for three different MWNT contents (3 15 and 40 wt%) within the films. The results indicated that the values of the diffusion coefficient D are strongly dependent on both temperature and MWNT content in the film. It was also observed that the diffusion coefficients obey Arrhenius behavior from which diffusion energies were determined which increased with increase of MWNT content and temperature. (C) 2013 Elsevier B.V. All rights reserved.Article Citation Count: 1Fluorescence study of film formation from PS/Al2O3 nanocomposites(Elsevier Science, 2014) Pekcan, Önder; Uğur, Şaziye; Sunay, M. SelinSteady state fluorescence (SSF) and UV-vis (UVV) techniques were used to study the film formation behavior of pyrene (P) labeled polystyrene (PS) latex and Al2O3 (PS/Al2O3) composites depending on PS particles size and Al2O3 content. The close-packed arrays of PS spheres (SmPS: 203 nm ; LgPS: 382 nm) templates on clean glass substrates were covered with various layers of Al2O3 by dip-coating method. Two different film series (SmPS/Al2O3 and LgPS/Al2O3) were prepared in various Al2O3 layer content. The film formation behavior of these composites were studied by annealing them at a temperature range of 100-250 degrees C and monitoring the scattered light intensity (I-sc) fluorescence intensity (I-p) from P and transmitted light intensity (I-tr) through the films after each annealing step. Optical results indicate that classical latex film formation was occurred for all Al2O3 content films and film formation process was unaffected by the Al2O3 content for both film series. Extraction of PS template produced highly ordered porous structures for high Al2O3 content in both film series. SEM images showed that the pore size and porosity could be easily tailored by varying the PS particle size and the Al2O3 content. (C) 2014 Elsevier B.V. All rights reserved.Article Citation Count: 3Fractal dimension and phase transition of graphene oxide (GO) doped polyacrylamide(ELSEVIER SCI LTD, 2020) Evingür, Gülşen Akın; Pekcan, ÖnderGraphene Oxide (GO)- Polyacrylamide composites prepared between 5 and 50 mu l GO were performed by Fluorescence Spectroscopy. The phase transition performed on the composites was measured by calculating the critical exponents, beta and gamma, respectively. In addition, fractal analysis of the composites was calculated by a fluorescence intensity of 427 nm. The geometrical distribution of GO in the composites was calculated based on the power law exponent values using scaling models. While the gelation proceeded GO plates first organized themselves into a 3D percolation cluster with the fractal dimension (D-f) of the composite, D-f = 2.63, then After it goes to diffusion limited clusters with D-f = 1.4, its dimension lines up to a Von Koch curve with a random interval of D-f = 1.14.Article Citation Count: 10Holocene climate forcings and lacustrine regime shifts in the Indian summer monsoon realm(Wıley, 2020) Eroğlu, Deniz; Marwan, Norbert; Eroğlu, Deniz; Goswami, Bedartha; Mishra, Praveen Kuma; Gaye, Birgit; Anoop, Akhil; Stebich, Martina; Jehangir, Arshid; Basavaiah, NathaniExtreme climate events have been identified both in meteorological and long-term proxy records from the Indian summer monsoon (ISM) realm. However, the potential of palaeoclimate data for understanding mechanisms triggering climate extremes over long time scales has not been fully exploited. A distinction between proxies indicating climate change, environment, and ecosystem shift is crucial for enabling a comparison with forcing mechanisms (e.g. El-Nino Southern Oscillation). In this study we decouple these factors using data analysis techniques [multiplex recurrence network (MRN) and principal component analyses (PCA)] on multiproxy data from two lakes located in different climate regions - Lonar Lake (ISM dominated) and the high-altitude Tso Moriri Lake (ISM and westerlies influenced). Our results indicate that (i) MRN analysis, an indicator of changing environmental conditions, is associated with droughts in regions with a single climate driver but provides ambiguous results in regions with multiple climate/environmental drivers; (ii) the lacustrine ecosystem was 'less sensitive' to forcings during the early Holocene wetter periods; (iii) archives in climate zones with a single climate driver were most sensitive to regime shifts; (iv) data analyses are successful in identifying the timing of onset of climate change, and distinguishing between extrinsic and intrinsic (lacustrine) regime shifts by comparison with forcing mechanisms. Our results enable development of conceptual models to explain links between forcings and regional climate change that can be tested in climate models to provide an improved understanding of the ISM dynamics and their impact on ecosystems. (c) 2020 John Wiley & Sons, Ltd.Conference Object Citation Count: 0Investigation of allosteric communication pathways in human beta 2-adrenergic receptor(Wiley-Blackwell, 2015) Akdaş, Başak; Kürkçüoğlu, Özge; Doruker, Pemra; Akten, Ebru Demet[Abstract Not Available]Article Citation Count: 6Investigation of PSt-MWCNT concentration on epoxyacrylate photopolymerization and conductivity of polymer films(Elsevier Science SA, 2013) Doğruyol, Zekeriya; Temel, Gökhan; Doğruyol, Sevnur Keskin; Pekcan, Önder; Arsu, NergisPhotopolymerization kinetics and conductivity changes of epoxyacrylate composites for various loading modified PSt-MWCNT weight fractions changing from 0.0025 to 0.2 wt.% were evaluated by performing photo differential scanning calorimetry (photo-DSC) and four point conductivity measurements. 0.2% PSt-MWCNT additive polymeric films had their electrical conductivity boosted by 6% more than non-additive polymeric films. (C) 2012 Elsevier B.V. All rights reserved.Article Citation Count: 17Multifaceted Dynamics of Janus Oscillator Networks(Amer Physical Soc., 2019) Eroğlu, Deniz; Eroğlu, Deniz; Motter, Adilson E.Recent research has led to the discovery of fundamental new phenomena in network synchronization including chimera states explosive synchronization and asymmetry-induced synchronization. Each of these phenomena has thus far been observed only in systems designed to exhibit that one phenomenon which raises the questions of whether they are mutually compatible and if so under what conditions they co-occur. Here we introduce a class of remarkably simple oscillator networks that concurrently exhibit all of these phenomena. The dynamical units consist of pairs of nonidentical phase oscillators which we refer to as Janus oscillators by analogy with Janus particles and the mythological figure from which their name is derived. In contrast to previous studies these networks exhibit (i) explosive synchronization with identical oscillators, (ii) extreme multistability of chimera states including traveling intermittent and bouncing chimeras, and (iii) asymmetry-induced synchronization in which synchronization is promoted by random oscillator heterogeneity. These networks also exhibit the previously unobserved possibility of inverted synchronization transitions in which a transition to a more synchronous state is induced by a reduction rather than an increase in the coupling strength. These various phenomena are shown to emerge under rather parsimonious conditions and even in locally connected ring topologies which has the potential to facilitate their use to control and manipulate synchronization in experiments.Article Citation Count: 43New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies(Elsevier France-Editions Scientifiques Medicales Elsevier, 2017) Eşsiz, Şebnem; Saraç, Selma; Sarı, Suat; Kart, Didem; Eşsiz, Şebnem; Vural, İmran; Dalkara, SevimAzole antifungals are potent inhibitors of fungal lanosterol 14 alpha demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design synthesis and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl) ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 mu g/mL against Candida albicans. Additionally some of our compounds such as 19 (MIC: 0.25 mu g/mL) were potent against resistant C. glabrata a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action we performed computational analysis utilizing molecular docking and dynamics simulations on the C. albicans and C. glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19. (C) 2017 Elsevier Masson SAS. All rights reserved.Article Citation Count: 41New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes(Company of Biologists Ltd, 2017) Abekhoukh, Sabiha; Şahin, H. Bahar; Grossi, Mauro; Zongaro, Samantha; Maurin, Thomas; Madrigal, Irene; Kazue-Sugioka, Daniele; Raas-Rothschild, Annick; Doulazmi, Mohamed; Carrera, Pilar; Stachon, Andrea; Scherer, Steven; Do Nascimento, Maria Rita Drula; Trembleau, Alain; Arroyo, Ignacio; Szatmari, Peter; Smith, Isabel M.; Mila, Montserrat; Smith, Adam C.; Giangrande, Angela; Caille, Isabelle; Bardoni, BarbaraCytoplasmic FMRP interacting protein 1 (CYFIP1) is a candidate gene for intellectual disability (ID) autism schizophrenia and epilepsy. It is a member of a family of proteins that is highly conserved during evolution sharing high homology with its Drosophila homolog dCYFIP. CYFIP1 interacts with the Fragile X mental retardation protein (FMRP encoded by the FMR1 gene) whose absence causes Fragile X syndrome and with the translation initiation factor eIF4E. It is a member of theWAVE regulatory complex (WRC) thus representing a link between translational regulation and the actin cytoskeleton. Here we present data showing a correlation between mRNA levels of CYFIP1 and other members of the WRC. This suggests a tight regulation of the levels of the WRC members not only by post-translational mechanisms as previously hypothesized. Moreover we studied the impact of loss of function of both CYFIP1 and FMRP on neuronal growth and differentiation in two animal models -fly and mouse. We show that these two proteins antagonize each other's function not only during neuromuscular junction growth in the fly but also during new neuronal differentiation in the olfactory bulb of adult mice. Mechanistically FMRP and CYFIP1 modulate mTor signaling in an antagonistic manner likely via independent pathways supporting the results obtained in mouse as well as in fly at the morphological level. Collectively our results illustrate a new model to explain the cellular roles of FMRP and CYFIP1 and the molecular significance of their interaction.
