dina mostafa - Academia.edu (original) (raw)

Papers by dina mostafa

This is the result of RNAseq analysis of control and Cnot3βKO islets by edgeR .

We performed gene set enrichment analysis (GSEA) of β cell-disallowed genes identified by Pullen ... more We performed gene set enrichment analysis (GSEA) of β cell-disallowed genes identified by Pullen et al, 2017; Frontiers in Genetics, which revealed enrichment of a number of β cell-disallowed genes in our transcriptome data set.

TUNEL assay performed on pancreatic sections from 8-week-old control and Cnot3βKO male mice. TUNE... more TUNEL assay performed on pancreatic sections from 8-week-old control and Cnot3βKO male mice. TUNEL assay revealed no obvious β cell death in Cnot3βKO mice. Negative control: Pancreatic section from control mouse treated with labeling solution without terminal transferase. Positive control: Pancreatic section from control mouse treated with DNase. A white scale bar represents 50 μm. All images were taken at the same magnification.

Immunofluorescence of CNOT3 (green) in islets from 8-week-old control and Cnot3</i&gt... more Immunofluorescence of CNOT3 (green) in islets from 8-week-old control and Cnot3βKO mice. Nuclei were stained with DAPI (blue). A scale bar represents 50 µm. All images were taken at the same magnification.

Co-immunofluorescence staining of EGFP (green), insulin (magenta) and DAPI (blue) in pancreatic s... more Co-immunofluorescence staining of EGFP (green), insulin (magenta) and DAPI (blue) in pancreatic sections from 8-week-old control and Cnot3βKO mice. A scale bar represents 25 µm. Representative results from three 8-week-old mice from each genotype are shown. All images were taken at the same magnification.

Communications Biology, 2020

Pancreatic β-cells are responsible for production and secretion of insulin in response to increas... more Pancreatic β-cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Defects in β-cell function lead to hyperglycemia and diabetes mellitus. Here, we show that CNOT3, a CCR4–NOT deadenylase complex subunit, is dysregulated in islets in diabetic db/db mice, and that it is essential for murine β cell maturation and identity. Mice with β cell-specific Cnot3 deletion (Cnot3βKO) exhibit impaired glucose tolerance, decreased β cell mass, and they gradually develop diabetes. Cnot3βKO islets display decreased expression of key regulators of β cell maturation and function. Moreover, they show an increase of progenitor cell markers, β cell-disallowed genes, and genes relevant to altered β cell function. Cnot3βKO islets exhibit altered deadenylation and increased mRNA stability, partly accounting for the increased expression of those genes. Together, these data reveal that CNOT3-mediated mRNA deadenylation and decay constitute previously un...

High Flux Isotope Reactor (HFIR) highly enriched uranium (HEU) to low-enriched uranium (LEU) conv... more High Flux Isotope Reactor (HFIR) highly enriched uranium (HEU) to low-enriched uranium (LEU) conversion activities are ongoing as part of the Department of Energy (DOE) National Nuclear Security Administration (NNSA)'s nuclear nonproliferation mission. Design activities studying the conversion of HFIR from HEU to LEU fuel explored different fuel design features and shapes with a low density uranium-silicide dispersion (U 3 Si 2-Al) fuel, which has a uranium density of 4.8 gU/cm 3. The goal of these studies is to generate several HFIR LEU fuel designs of varying fuel fabrication complexity that meet the current HEU performance metrics and safety requirements. The documented designs will serve as references for fuel fabrication and qualification activities. Recent advancements in modeling and simulation tools enable quick prototyping of fuel designs. Shift, a Monte Carlo neutron transport and depletion tool optimized for high-performance computing (HPC) architectures, is used for efficient fuel cycle and performance metrics calculations. The HFIR Steady State Heat Transfer Code (HSSHTC) is used to vet the thermal safety margin. Also, a new automation tool that connects all fuel design analysis steps, named Python HFIR Analysis and Measurement Engine (PHAME), has been developed to expedite the design study in an efficient and reproducible manner. Leveraging these tools, several candidate fuel designs were selected for varying fabrication complexity. This report provides design feature details for four selected HFIR LEU low density U 3 Si 2-Al fuel designs and their corresponding performance and safety metrics. Nominal, best-estimate design parameters and irradiation conditions, including fission rate densities, power densities, heat fluxes, and cumulative fission densities are provided for candidate fuel designs relevant to framing irradiation experiments to support fuel qualification efforts. Simulations show that the low density U 3 Si 2-Al, with design features to enhance safety, can meet HEU core performance metrics and safety requirements if the reactor power is increased from 85 MW (HEU) to 95 MW (LEU) and if the active fuel length is increased from 50.80 cm (HEU) to 55.88 cm (LEU). * This Q value of 200.7 Mev/fission is a 'typical' Q value used in HFIR analyses close to the approximate cycle-averaged value that was recently calculated for the optimized silicide design. The BOC and EOC Q values were estimated to be 200.49 and 201.46 MeV/fission, respectively, givin the average Q value of 200.98 MeV/fission [9].

Transactions of the American Nuclear Society - Volume 123, 2020

RNA Biology, 2020

Shortening of mRNA poly(A) tails (deadenylation) to trigger their decay is mediated mainly by the... more Shortening of mRNA poly(A) tails (deadenylation) to trigger their decay is mediated mainly by the CCR4-NOT deadenylase complex. While four catalytic subunits (CNOT6, 6L 7, and 8) have been identified in the mammalian CCR4-NOT complex, their individual biological roles are not fully understood. In this study, we addressed the contribution of CNOT7/8 to viability of primary mouse embryonic fibroblasts (MEFs). We found that MEFs lacking CNOT7/8 expression [Cnot7/8-double knockout (dKO) MEFs] undergo cell death, whereas MEFs lacking CNOT6/6L expression (Cnot6/6l-dKO MEFs) remain viable. Co-immunoprecipitation analyses showed that CNOT6/6L are also absent from the CCR4-NOT complex in Cnot7/8-dKO MEFs. In contrast, either CNOT7 or CNOT8 still interacts with other subunits in the CCR4-NOT complex in Cnot6/6l-dKO MEFs. Exogenous expression of a CNOT7 mutant lacking catalytic activity in Cnot7/8-dKO MEFs cannot recover cell viability, even though CNOT6/6L exists to some extent in the CCR4-NOT complex, confirming that CNOT7/8 is essential for viability. Bulk poly(A) tail analysis revealed that mRNAs with longer poly(A) tails are more numerous in Cnot7/8-dKO MEFs than in Cnot6/6l-dKO MEFs. Consistent with elongated poly(A) tails, more mRNAs are upregulated and stabilized in Cnot7/8-dKO MEFs than in Cnot6/6l-dKO MEFs. Importantly, Cnot6/6l-dKO mice are viable and grow normally to adulthood. Taken together, the CNOT7/8 catalytic subunits are essential for deadenylation, which is necessary to maintain cell viability, whereas CNOT6/6L are not.

Diabetes, 2018

Loss of β-cell identity, dedifferentiation and reprogramming are recognized as mechanisms of β-ce... more Loss of β-cell identity, dedifferentiation and reprogramming are recognized as mechanisms of β-cell dysfunction in diabetes. Molecular β-cell identity is not only defined by the expression of signature functional β-cell specific genes but also the repression of several genes recently identified in β-cell research as β-cell disallowed genes. The molecular mechanisms involved in the repression of β-cell disallowed genes are largely unknown. Here, we show that the CCR4-NOT complex, a major deadenylase conserved in eukaryotes, is involved in post-transcriptional regulation of β-cell disallowed genes. β-cell specific depletion of CNOT3 (CNOT3βKO), a CCR4-NOT complex subunit, in mice promotes deceased insulin secretion, early impaired glucose tolerance and the development of overt diabetes at 12 weeks of age. CNOT3βKO islets display decreased insulin content and decreased glucose responsiveness. Furthermore, CNOT3 depleted ß cells exhibit ultrastructural abnormalities including: degranula...

Diabetes, 2019

Slc16a1 gene belongs to a family of genes that are selectively silenced in mature β-cells as comp... more Slc16a1 gene belongs to a family of genes that are selectively silenced in mature β-cells as compared to other mammalian cell types and thereby named “β-cell disallowed genes.” Forced expression of Slc16a1 in β-cells interfered with insulin secretion and normal β-cell function. Slc16a1 is previously shown to be regulated by promoter methylation transcriptionally and miRNA post-transcriptionally. Here, we show deadenylation by CCR4-NOT complex is involved in silencing of Slc16a1 and maintaining normal β-cell function. We have previously shown that β-cell specific knockout of CNOT3 (CNOT3βKO), a CCR4-NOT complex and a positive modulator of its function causes upregulation of β-cell disallowed genes among them is Slc16a1 alongside with the decreased expression of β-cell specific genes and loss of normal β-cell function. In this study, we demonstrate the molecular mechanism by which CCR4-NOT complex is involved in silencing Slc16a1. Slc16a1 mRNA is stabilized in CNOT3βKO islets compared...

Annals of Nuclear Energy, 2019

An iterative design process involving neutronic and thermal-hydraulic modeling and simulation has... more An iterative design process involving neutronic and thermal-hydraulic modeling and simulation has been employed to assess the feasibility of converting the Oak Ridge National Laboratory (ORNL) High Flux Isotope Reactor (HFIR) from high-enriched uranium (HEU) to low-enriched uranium (LEU) silicide dispersion fuel. ORNL is funded by the National Nuclear Security Administration to evaluate HFIR conversion. Previous HFIR conversion studies focused on U-10Mo monolithic fuel; however, due to potential fabrication issues with the complex HFIR U-10Mo fuel design, ORNL is evaluating U 3 Si 2-Al dispersion fuel as an alternative LEU fuel system. Fueled by 10.1 kg of HEU and operated at 85 MW, HFIR provides one of the highest steady-state neutron fluxes of any research reactor in the world. Retrofitting a compact, high-power density, HEU-based core with LEU is a challenging problem to solve, especially when considering the conversion requirements. Neutronic and thermal-hydraulic analyses were performed with Shift and HSSHTC, respectively, to predict reactor performance and thermal safety margins. A number of designs were proposed and evaluated using an iterative approach in an effort to show that reactor performance could match that obtained using HEU fuel and that thermal safety margins were adequate. This study concludes that conversion of HFIR with U 3 Si 2-Al LEU fuel is feasible if, among other requirements, the fuel meat region is centered and symmetric about the fuel plate thickness centerline, the active fuel zone length is increased from 50.80 cm to 55.88 cm, the proposed fabrication tolerances can be met, and the fuel can be qualified for HFIR conditions.

The purpose of this report is to document a high-fidelity VESTA/MCNP High Flux Isotope Reactor (H... more The purpose of this report is to document a high-fidelity VESTA/MCNP High Flux Isotope Reactor (HFIR) core model that features a new, representative experiment loading. This model, which represents the current, high-enriched uranium fuel core, will serve as a reference for low-enriched uranium conversion studies, safety-basis calculations, and other research activities. A new experiment loading model was developed to better represent current, typical experiment loadings, in comparison to the experiment loading included in the model for Cycle 400 (operated in 2004). The new experiment loading model for the flux trap target region includes full length 252 Cf production targets, 75 Se production capsules, 63 Ni production capsules, a 188 W production capsule, and various materials irradiation targets. Fully loaded 238 Pu production targets are modeled in eleven vertical experiment facilities located in the beryllium reflector. Other changes compared to the Cycle 400 model are the high-fidelity modeling of the fuel element side plates and the material composition of the control elements. Results obtained from the depletion simulations with the new model are presented, with a focus on time-dependent isotopic composition of irradiated fuel and single cycle isotope production metrics.

A concerted effort over the past few years has been focused on enhancing the core model for the H... more A concerted effort over the past few years has been focused on enhancing the core model for the High Flux Isotope Reactor (HFIR), as part of a comprehensive study for HFIR conversion from high-enriched uranium to low-enriched uranium (LEU) fuel. At this time, the core model used to perform analyses in support of HFIR operation is a Monte Carlo model with the MCNP code for the beginning of Cycle 400, which was documented in detail in a 2005 technical report. An updated HFIR core depletion model that is based on current state-of-the-art methods and nuclear data was needed to serve as reference for the design of an LEU fuel for HFIR. The recent enhancements in modeling and simulations for HFIR that are discussed in the present report include: (1) revision of the 2005 MCNP model for the beginning of Cycle 400 to improve the modeling data and assumptions as necessary based on appropriate primary reference sources-HFIR drawings and reports; (2) improvement of the fuel region model, including an explicit representation for the involute fuel plate geometry that is specific to HFIR fuel; and (3) revision of the Monte Carlo-based depletion model for HFIR, in use since 2009 but never documented in detail, with the development of a new depletion model for the HFIR explicit fuel plate representation. The new HFIR models for Cycle 400 are used to determine various metrics of relevance to reactor performance and safety assessments. The calculated metrics are compared, where possible, with measurement data from preconstruction critical experiments at HFIR, data included in the current HFIR safety analysis report, and/or data from previous calculations performed with different methods or codes. The results of the analyses show that the models presented in this report provide a robust and reliable basis for HFIR analyses.

Journal of Molecular Liquids, 2015

Cumin is an annual herb from Apiaceae family. Cumin seeds possess good content of phenolic compou... more Cumin is an annual herb from Apiaceae family. Cumin seeds possess good content of phenolic compounds which show considerable free radical scavenging activity. Nanoemulsions (NEs) can be used as a vehicle for transport of pharmaceutical phytochemicals through the stratum corneum barrier because of their stability and rapid permeation properties. The objective of this work is to encapsulate cumin essential oil (CEO) in transdermal nanoemulsion formulations to acquire efficient and prolonged systemic antioxidant and hepatoprotective activities. Six phase diagrams were constructed comprising Capryol™ 90 or oleic acid as the oil phase along with three surfactant/co-surfactant (Smix) ratios; 1:1, 2:1, and 3:1 of Tween 20/ethanol. From each, one nanoemulsion system was selected. The prepared CEO loaded NEs showed high phenolic encapsulation efficiency as well as remarkable cumulative phenols permeation through rat skin. Four formulations, with appreciable permeation results, revealed good thermodynamic stability and physicochemical properties. The formulation S5, containing cumin essential oil/oleic acid; oil phase, Tween 20/ethanol (2:1); Smix and distilled water, proved to be the most promising formula considering the in-vitro and in-vivo antioxidant efficiency, provided high hepatoprotective potential and reserved rats' body weight after a period of seven days of a single transdermal application. Such formulation would provide efficient antioxidant and hepatoprotective activities as well as successful protection from various chronic diseases via a single weakly transdermal application.

Current Drug Delivery, 2015

Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes kno... more Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time . Of boswellic acids, 3- acetyl - 11- keto - β - boswellic acid (AKBA) is the most potent anti- inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced ant i- inflammatory activity, in comparison with the standard oral anti - inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was conducted at 210 nm using UV / Vis detector. A solubility study for the bioactive fraction was conducted . Microcrystalline cellulose and Aeroperl® 300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s flow index were estimated. Six systems were prepared using polyethylene glycol 400 , solvent and two drug loading concentrations ; 20 and 40 %. For each concentration , three carrier : coat ratios were dispensed ; 20:1 , 10:1 , and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investig ating upper GIT ulcerogenic effect and anti- inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti- inflammatory efficacy for formulations F 1 and F2, with carrier : coat ratio, 5:1 and drug loads of 20 and 40 % , respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive faction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.

Journal of Drug Delivery Science and Technology, 2015

ABSTRACT Foeniculum vulgare Mill., family Umbelliferae, is well known for its essential oil. One ... more ABSTRACT Foeniculum vulgare Mill., family Umbelliferae, is well known for its essential oil. One of the major components of Foeniculum vulgare seed’s essential oil is transanethole. Foeniculum vulgare (fennel) possesses antioxidant and antidiabeic activities. Transdermal nanoemulsions (NEs) were employed to encapsulate fennel essential oil (FEO) with the aim of attaining effective prolonged antidiabetic action. A large NE existence area was obtained on phase diagrams employing oleic acid; oil phase and Tween20/propylene glycol; Smix in the ratios 1:1, 2:1 and 3:1 and water. Encapsulation efficiency was evaluated for transanethole (TA) by HPLC analysis and reached 64 % in the prepared NEs. NEs were characterized for thermodynamic stability, conductivity, pH, particle size and zeta potential. Values obtained were promising. Permeation profiles for 24h showed the superiority of FEO NE, F1, which showed also a high potential of reducing plasma glucose levels in rats which continued for 7-days after a single TD application of a dose of 120 mg/Kg of FEO. These results highlight the high efficiency of F1, formed of 2% FEO, 5.6% oleic acid, 68% Smix (1:1) and distilled water, in bringing glucose levels to normal in diabetic rats.

International journal of pharmaceutical compounding

Rice bran oil and its bioactive constituents have been reported to possess different health benef... more Rice bran oil and its bioactive constituents have been reported to possess different health benefit effects. Rice bran oil-containing pharmaceutical and cosmeceutical formulae are dispensed and characterized to elucidate the impact of their properties on clinical applications. Liquisolid and semisolid formulations employing rice bran oil were dispensed and characterized. Semisolid formulae were characterized for organoleptic properties, rheological behavior, and physical stability, at zero time and after three months storage, at 30 degrees C and 40 degrees C. Patch test of transdermal emollient creams and sunscreen was conducted in addition to evaluation of sensory attributes of emollient cream and sunscreen. Liquisolid formulations revealed flow and bulk density figures close to those reported as optimum acceptable values for powders. Semisolid formulations revealed adequate properties after three months of storage compared with zero time. Patch test showed safety of transdermal an...