In the pursuit of the fear engram: identification of neuronal circuits underlying the treatment of anxiety disorder

Fear and other anxiety disorders are extraordinarily robust and difficult to treat. Among the most effective treatments for anxiety disorders are exposure-based therapies, during which a patient is repeatedly confronted with the originally fear-eliciting stimulus in a safe environment so that the once fearful stimulus can be newly interpreted as neutral or safe. A fundamental element for successful exposure-based therapies is the reactivation/recall of the traumatic memory, which initiates a time-limited process called memory reconsolidation, during which a memory becomes susceptible to disruption. Presently, the neuronal subpopulations and molecular mechanisms underlying successful fear memory attenuation remain completely unknown, which represents a big gap in memory research. Therefore, the aim of this work is to first identify the neuronal subpopulations that are causally implicated in effective attenuation of remote fear memories. This will help to determine whether the original traumatic memory trace has been permanently modified or a new memory trace of safety has been superimposed over the original one. The second aim is to develop a tool that allows for the isolation of the neuronal subpopulations causally implicated in remote memory attenuation, in order to be able to delineate the epigenetic and transcriptional mechanisms at play within these subpopulations. This will help to identify a molecular signature of effective remote fear memory attenuation. The results of my research suggest for the first time that there is a small population of neurons in the dentate gyrus - that was active during the recall of fear â that needs to be reactivated during extinction to attain successful remote fear attenuation. While the inactivation of such population during extinction impairs fear attenuation, its activation ameliorates behavioral extinction. Furthermore, I have successfully established a method to isolate this neuronal subpopulation from the brain, namely by fluorescence-activated cell sorting. This tool will allow follow up studies to pursue the quest for the molecular signature of successful remote memory attenuation. Overall, these findings could help us to better understand the intricate principles of effective remote fear memory attenuation, and thus to develop new strategies that improve the treatment of anxiety disorder

Synthesis and antimicrobial activities of some novel bis-pyrazole derivatives containing a hydrophosphoryl unit

Vilsmeier-Haack reaction conditions were applied on some methyl ketone aryl phosphonicdihydrazones to yield some interesting bis-pyrazole derivatives containing a hydro-phosphoryl unit. Bis-{4-formyl-3-aryl-1H-pyrazol-1-yl}phosphine oxides (4a,b) were condensed with some nucleophiles such as aniline, phenacyltriphenylphosphonium bromide and 4-phenylthiosemicarbazide followed by treatment with thioglycolic acid, diethyl phosphite and/or acetic anhydride to yield a novel class of bis-pyrazoles containing sulfur and phosphorus derivatives. Most of the newly synthesized compounds were evaluated for their in vitro antimicrobial activities

A new natural pyrrolone from the Egyptian Ageratum species

Ageratum conyzoides L., is an annual herb with a long history of traditional medicinal uses in many countries in the world, especially in the tropical and subtropical regions. A wide range of chemical compounds including alkaloids, flavonoids, chromenes, benzofurans and terpenoids have been isolated from this species. Extracts and metabolites from this plant have been found to possess pharmacological and insecticidal activities. In continuation of our interest in the Egyptian medicinal plants, the reinvestigation of the methylenechloride extract of the air-dried aerial parts of Ageratum conyzoides afforded a new natural compound 1, pyrrolone, 5-ethoxy-1H-pyrrol-2(5H)-one, together with a known flavonoid. The structures of the compounds were determined by comprehensive NMR studies, including DEPT, COSY, HMQC, HMBC, and MS

An efficient cyclocondensation reactions, antimicrobial activity and molecular orbital calculations of α-benzopyrone derivatives

An efficient synthesis of 4,6,8-trimethyl-2-oxo-2H-chromene-3-carbonitrile (2) via Claisen condensation of 3,5-dimethyl-2-hydroxyacetophenone with ethyl cyanoacetate in the presence of sodium metal is reported. Cyclocondensation reactions of compound (2) with ethyl acetate or with ethyl cyanoacetate in the presence of ethoxide gave sodium salt of 7-amino-9-hydroxy-2,4-dimethyl-6H-benzo[c]chromen-6-one derivatives (3) and (4) respectively, which upon neutralization with 10 % hydrochloric acid gave 7-amino-9-hydroxy-2,4-dimethyl-6H-benzo[c]chromen-6-one (5). Hydrolysis of compound (2) with ethanolic sodium hydroxide solution gave 4,6,8-trimethyl-2-oxo-2H-chromene-3-carboxylic acid (6). Treatment of compound (2) with Vilsmier reagent using excess POCl3 gave 4-(chloro(formyl)methyl-6,8-dimethyl-2-oxo-2H-chromene-3-carbonitrile (7). Also, conden-sation of compound (2) with DMF-DMA in xylene or with POCl3/DMF in pyridine gave the same product 4-((E)-2-(dimethylamino)vinyl)-6,8-dimethyl-2-oxo-2H-chromene-3-carbo-nitrile (8). The cyclocondensation reactions of compound (8) with hydroxylamine hydrochloride, urea, and with hydrazinecarbodithioic acid gave 3,4-dihydro-3-hydroxy-4-imino-7,9-dimethylchromeno[3,4-c]pyridin-5-one (9), 4-imino-7,9-dimethyl-5-oxo-4H-chro-meno[3,4-c]pyridine-3(5H)-carboxamide (10) and 3-amino-3,4-dihydro-4-imino-7,9-dimethyl chromeno[3,4-c]pyridin-5-one (11), respectively. Also, acid hydrolysis of compound (8) gave 7,9-dimethyl-3H-chromeno[3,4-c]pyridine-4,5-dione (12). Structures of the products were established on the basis of elemental analysis, IR, 1H and 13C NMR, mass spectra and semi-empirical AM1-MO calculations. The antimicrobial activities of the synthesized products were also studied

Synthesis, antifungal activity and semi-empirical AM1-MO calculations of some new 4-oxo-4H-chromene derivatives

Some new antifungal agents have been prepared through reaction of 4-oxo-4H-chromene-3-carbaldehydes (1a,b) with some active primary amines (2a-e) and amides/thioamides (6a-d) in different conditions. Structures of the products were established on the basis of elemental analysis, IR, 1H NMR, mass spectra and semi-empirical AM1-MO calculations

Bioremoval capacity of phenol by some selected endophytic fungi isolated from Hibiscus sabdariffa and batch biodegradation of phenol in paper and pulp effluents

Background and Objectives: The use of endophytic fungi for management of phenol residue in paper and pulp industries has been shown as cost-effective and eco-friendly approach. In this study, isolation of endophytic fungi from roots, stems, and leaves of Hibiscus sabdariffa was conducted. Additionally, the isolated fungi were examined for their ability to degrade phenol and its derivatives in paper and pulp industrial samples, using different growth conditions. Materials and Methods: Out of 35 isolated endophyitc fungi, 31 were examined for their phenol biodegradation capacity using Czapek Dox broth medium containing Catechol and Resorcinol as a sole carbon source at final concentrations of 0.4, 0.6 and 0.8%. Results: A total of 35 fungal species belonging to 18 fungal genera were isolated and identified from different parts of H. sabdariffa plants. All strains have the capability for degrading phenol and their derivatives with variable extents. The optimum condition of degrading phenol in paper and pulp effluent samples by Fusarium poae11r7 were at pH 3-5, temperature at 28-35°C, good agitation speed at no agitation and 100 rpm. Conclusion: All endophytic fungal species can utilize phenol and its derivatives as a carbon source and be the potential to degrade phenol in industrial contaminants

Adaptive Fuzzy Supplementary Controller for SSR Damping in a Series-Compensated DFIG-Based Wind Farm

Although using a series compensation technique in a long transmission line effectively increases the transmittable power; it may cause a sub-synchronous resonance (SSR) phenomenon. Gate-controlled series capacitor (GCSC) is an effective method for SSR damping by controlling the turn-off angle. In the previous studies, a constant supplementary damping controller (SDC) was used for controlling the turn-off angle, which can mitigate the SSR phenomenon. However, these methods can not capture the maximum transmittable power at different operating points. In this paper, a fuzzy logic controller (FLC) is proposed to compute the gain of SDC based on the wind speed and the error between the measured and reference line currents for transferring as much power as possible and damping the SSR phenomenon simultaneously. Using the MATLAB/SIMULINK program, the proposed method is tested at different operating points to validate its effectiveness and robustness. Compared to the traditional method (constant SDC), the maximum transmittable power, as well as SSR damping, is achieved in all studied cases by the proposed method (variable SDC)

Influence of blend ratio on the electrical characteristics of vulcanized SBR/NBR blends compatibilized by Cis-polybutadiene rubber

Blends composed of styrene butadiene rubber (SBR) and acrylonitrile-butadiene rubber (NBR) have been fabricated by melt-blending technique using two-roll mill blend machine. Cis-polybutadiene rubber (CBR) was used as a compatibilizer for enhancing the homogeneity between blend phases. No previous reports were found to discuss improving electrical properties of vulcanized SBR/NBR blends using unfilled rubber system (i.e. no fillers incorporation). SEM micrographs were utilized to verify the compatibility between two rubber ingredients in various blends, owing to the use of compatibilizer. Thermal stability of blends was investigated by differential thermal analysis (DTA) and differential scanning calorimetric (DSC) to evaluate the influence of blend ratio on the compatibility of investigated samples. Results revealed that the dielectric properties of blends are dramatically influenced by altering the blend ratio. The results revealed that the SEM observations confirmed the compatibilization effect of CBR on vulcanized SBR/NBR blends. Meanwhile, thermal properties of vulcanized SBR/NBR blends were enhanced with increasing of SBR contents in blends. The complex impedance graphs showed circular arcs showing the bulk contribution to overall electrical behavior for investigated vulcanized SBR/NBR blends. During I-V characteristics have been presented, where a remarkably change from linear behavior to nonlinear conduction at lower temperatures was found for 0SBR/100NBR blends. These findings supported and confirmed that the compatibilization effect and the blend ratio between rubber compositions have strongly influenced on their thermal and electrical properties of vulcanized blends

Detection of Helicobacter pylori oipA and dupA genes among dyspeptic patients with chronic gastritis

Helicobacter pylori (H. pylori): is a microbe with wide genetic diversity that infects the stomach of most people in developing countries, leading to several clinical outcomes among different individuals such as gastritis, ulcers, or gastric cancer. Outer inflammatory protein A (oipA) and duodenal ulcer promoting (dupA) genes are among the possible virulence factors which determine the patient outcome. Aim: To detect oipA and dupA genes of H. pylori among dyspeptic Egyptian patients, and to investigate their correlation with the varying degrees of the associated chronic gastritis. Methods: The study enrolled 50 patients with dyspepsia, attending the Gastrointestinal Endoscopy unit of the Gastroenterology and Tropical Departments at Ain Shams University Hospital for upper gastrointestinal endoscopy, in the period between, June and, December 2019. Four antral gastric biopsies were taken from each patient for polymerase chain reaction assay to detect the virulence genes oipA, dupA, and cagA and for histopathological assessment. Results: Forty patients were H. pylori positive by histopathology and PCR. cagA, oipA, and dupA were identified in 6 (15%), 13 (32.5%), 9 (22.5%) of biopsies, respectively. Both cagA and oipA genes were highly significantly associated with increasing the severity of gastritis. Only oipA virulence gene showed a highly significant association with gastroduodenitis. There was a highly significant moderate association between cagA and oipA genes. Conclusion: oipA could be a virulence biomarker that serves a great value in predicting the progress of gastric mucosal damage in patients with chronic gastritis, and targeting antimicrobial therapy in those patients to prevent severe gastroduodenal diseases