PubMed İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12469/4466

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Citation - WoS: 4
Citation - Scopus: 6
Abortion Services at Hospitals in Istanbul
(Taylor & Francis Ltd, 2017) O'Neil, Mary Lou
Objective: Despite the existence of a liberal law on abortion in Turkey there is growing evidence that actually securing an abortion in Istanbul may prove difficult. This study aimed to determine whether or not state hospitals and private hospitals that accept state health insurance in Istanbul are providing abortion services and for what indications. Method: Between October and December 2015 a mystery patient telephone survey of 154 hospitals 43 public and 111 private in Istanbul was conducted. Results: 14% of the state hospitals in Istanbul perform abortions without restriction as to reason provided in the current law while 60% provide the service if there is a medical necessity. A quarter of state hospitals in Istanbul do not provide abortion services at all. 48.6% of private hospitals that accept the state health insurance also provide for abortion without restriction while 10% do not provide abortion services under any circumstances. Key conclusions: State and private hospitals in Istanbul are not providing abortion services to the full extent allowed under the law. The low numbers of state hospitals offering abortions without restriction indicates a de facto privatization of the service. This same trend is also visible in many private hospitals partnering with the state that do not provide abortion care. While many women may choose a private provider the lack of provision of abortion care at state hospitals and those private hospitals working with the state leaves women little option but to purchase these services from private providers at some times subtantial costs.
Citation - WoS: 31
Citation - Scopus: 42
Acculturation Attitudes and Social Adjustment in British South Asian Children: a Longitudinal Study
(Sage Publications Inc, 2013) Brown, Rupert; Baysu, Gülseli; Cameron, Lindsey; Nigbur, Dennis; Rutland, Adam; Watters, Charles; Hossain, Rosa; LeTouze, Dominique; Landau, Anick
A 1-year longitudinal study with three testing points was conducted with 215 British Asian children aged 5 to 11 years to test hypotheses from Berry's acculturation framework. Using age-appropriate measures of acculturation attitudes and psychosocial outcomes it was found that (a) children generally favored an integrationist attitude and this was more pronounced among older (8-10 years) than in younger (5-7 years) children and (b) temporal changes in social self-esteem and peer acceptance were associated with different acculturation attitudes held initially as shown by latent growth curve analyses. However a supplementary time-lagged regression analysis revealed that children's earlier integrationist attitudes may be associated with more emotional symptoms (based on teachers' ratings) 6 months later. The implications of these different outcomes of children's acculturation attitudes are discussed.
Citation - WoS: 78
Citation - Scopus: 108
Air Quality Prediction Using Cnn Plus Lstm-Based Hybrid Deep Learning Architecture
(Springer Heidelberg, 2022) Gilik, Aysenur; Ogrenci, Arif Selcuk; Ozmen, Atilla
Air pollution prediction based on variables in environmental monitoring data gains further importance with increasing concerns about climate change and the sustainability of cities. Modeling of the complex relationships between these variables by sophisticated methods in machine learning is a promising field. The objectives of this work are to develop a supervised model for the prediction of air pollution by using real sensor data and to transfer the model between cities. The combination of a convolutional neural network and a long short-term memory deep neural network model was proposed to predict the concentration of air pollutants in multiple locations of a city by using spatial-temporal relationships. Two approaches have been adopted: the univariate model contains the information of one pollutant whereas the multivariate model contains the information of all pollutants and meteorology data for prediction. The study was carried out for different pollutants which are in the publicly available data of the cities of Barcelona, Kocaeli, and Istanbul. The hyperparameters of the model (filter, frame, and batch sizes; number of convolutional/LSTM layers and hidden units; learning rate; and parameters for sample selection, pooling, and validation) were tuned to determine the architecture that achieved the lowest test error. The proposed model improved the prediction performance (measured by the root mean square error) by 11-53% for particulate matter, 20-31% for ozone, 9-47% for nitrogenoxides, and 18-46% for sulfurdioxide with respect to the 1-hidden layer long short-term memory networks utilized in the literature. The multivariate model without using meteorological data revealed the best results. Regarding transfer learning, the network weights were transferred from the source city to the target city. The model has more accurate prediction performance with the transfer of the network from Kocaeli to Istanbul as those neighbor cities have similar air pollution and meteorological characteristics.
Citation - WoS: 2
Citation - Scopus: 2
Altered Dynamics of S. Aureus Phosphofructokinase Via Bond Restraints at Two Distinct Allosteric Binding Sites
(Academic Press Ltd- Elsevier Science Ltd, 2022) Celebi, Metehan; Akten, Ebru Demet
The effect of perturbation at the allosteric site was investigated through several replicas of molecular dynamics (MD) simulations conducted on bacterial phosphofructokinase (SaPFK). In our previous work, an alternative binding site was estimated to be allosteric in addition to the experimentally reported one. To highlight the effect of both allosteric sites on receptor's dynamics, MD runs were carried out on apo forms with and without perturbation. Perturbation was achieved via incorporating multiple bond restraints for residue pairs located at the allosteric site. Restraints applied to the predicted site caused one dimer to stiffen, whereas an increase in mobility was detected in the same dimer when the experimentally resolved site was restrained. Fluctuations in C-alpha-C-alpha distances which is used to disclose residues with high potential of communication indicated a marked increase in signal transmission within each dimer as the receptor switched to a restrained state. Cross-correlation of positional fluctuations indicated an overall decrease in the magnitude of both positive and negative correlations when restraints were employed on the predicted allosteric site whereas an exact opposite effect was observed for the reported site. Finally, mutual correspondence between positional fluctuations noticeably increased with restraints on predicted allosteric site, whereas an opposite effect was observed for restraints applied on experimentally reported one. In view of these findings, it is clear that the perturbation of either one of two allosteric sites effected the dynamics of the receptor with a distinct and contrasting character. (c) 2022 Elsevier Ltd. All rights reserved.
Citation - WoS: 10
Citation - Scopus: 13
Anterior Instrumentation for Adolescent Idiopathic Scoliosis
(Springer Verlag, 2001) Göğüş, Abdullah; Talu, Ufuk; Akman, Sümeyra; Sar, Can; Hamzaoğlu, Azmi; Eralp, Levent
Thirty-two patients with adolescent idiopathic scoliosis underwent anterior fusion with rigid single rod (third generation instrumentation) and titanium mesh cages. The mean follow-up was 31 (24-45) months and the mean age was 14.9 years. There were 8 patients with King type I 10 with type II 6 with type III 4 with type IV and 4 with lumbar curves. Titanium mesh cages were used in all the lumbar procedures and at the cranial and caudal ends of the instrumented area in thoracic cases. All the patients were immobilized in an orthosis for 3-6 months postoperatively. Mean preoperative primary coronal Cobb angle of 56 degrees was improved to 8.6 degrees. Average correction rate was 84%. Sagittal balance was restored with a mean thoracic kyphosis of 28 degrees and a mean lumbar lordosis of 38 degrees. Spontaneous secondary curve decompensation did not occur and postoperative thoracolumbar junctional kyphosis was not seen. One case had to be revised due to proximal screw pull out and loss of correction.
Citation - WoS: 8
Citation - Scopus: 9
Antifungal Screening and in Silico Mechanistic Studies of an In-House Azole Library
(2019) Sarı, Suat; Kart, Didem; Sabuncuoğlu, Suna; Doğan, İnci Selin; Özdemir, Zeynep; Bozbey, İrem; Gencel, Melis; Eşsiz, Şebnem; Reynisson, Jóhannes; Karakurt, Arzu; Saraç, Selma; Dalkara, Sevim
Systemic Candida infections pose a serious public health problem with high morbidity and mortality. C. albicans is the major pathogen identified in candidiasis; however, non-albicans Candida spp. with antifungal resistance are now more prevalent. Azoles are first-choice antifungal drugs for candidiasis; however, they are ineffective for certain infections caused by the resistant strains. Azoles block ergosterol synthesis by inhibiting fungal CYP51, which leads to disruption of fungal membrane permeability. In this study, we screened for antifungal activity of an in-house azole library of 65 compounds to identify hit matter followed by a molecular modeling study for their CYP51 inhibition mechanism. Antifungal susceptibility tests against standard Candida spp. including C. albicans revealed derivatives 12 and 13 as highly active. Furthermore, they showed potent antibiofilm activity as well as neglectable cytotoxicity in a mouse fibroblast assay. According to molecular docking studies, 12 and 13 have the necessary binding characteristics for effective inhibition of CYP51. Finally, molecular dynamics simulations of the C. albicans CYP51 (CACYP51) homology model's catalytic site complexed with 13 were stable demonstrating excellent binding.
Citation - WoS: 11
Citation - Scopus: 13
Antihepatitis B Response To Hepatitis B Vaccine Administered Simultaneously With Tetanus Toxoid in Nonresponder Individuals
(Elsevier Science, 2002) Sönmez, Emine; Sönmez, Ali Suha; Bayındır, Yaşar; Coşkun, Diler; Ariturk, Sedat
In this prospective study our aim was to test the effect of simultaneous administration of preS2 and S containing recombinant hepatitis B vaccine (S2SRHB) with tetanus toxoid (TT) to the individuals who did not respond after three doses of hepatitis B vaccine previously. There were three groups (healthy individuals pregnant women hemodialysis patients) each was divided into two subgroups as groups A and B. Group A received S2SRHB + TT and group B received only S2SRHB. We found that in groups receiving both vaccines both seroconversion rate and antibody titer level were significantly higher (P < 0.05). In conclusion simultaneous administration of S2SRHB + TT is more effective than administration of S2SRHB alone. (C) 2002 Elsevier Science Ltd. All rights reserved.
Citation - WoS: 1
Citation - Scopus: 1
Assessing Protein-Ligand Binding Modes With Computational Tools: the Case of Pde4b
(Springer, 2017) Çifii, Gülşah; Aviyente, Viktorya; Akten, Ebru Demet; Monard, Gerald
In a first step in the discovery of novel potent inhibitor structures for the PDE4B family with limited side effects we present a protocol to rank newly designed molecules through the estimation of their IC values. Our protocol is based on reproducing the linear relationship between the logarithm of experimental IC values [(IC)] and their calculated binding free energies (). From 13 known PDE4B inhibitors we show here that (1) binding free energies obtained after a docking process by AutoDock are not accurate enough to reproduce this linear relationship
Citation - WoS: 1
Citation - Scopus: 1
The Associations Between Deviation From the Balanced Time Perspective and Depression and Anxiety: The Moderator Role of Mindfulness in a Two-Wave Study
(Sage Publications inc, 2025) Altan-Atalay, Ayse; Ranjbar, Hamed Abdollahpour; Altintas, Seda
Deviation from the balanced time perspective (DBTP) refers to difficulties in switching between different time frames in a flexible way by considering the situational demands. DBTP is associated with higher levels of depression and anxiety. Mindfulness acts as a protective mechanism against depression and anxiety. The current study examined the moderator role of mindfulness in the relationship between DBTP and psychological distress. The participants were 243 university students (53.09% women) between ages 18 and 29 (M = 19.88, SD = 1.42) who answered self-report measures of time perspective, mindfulness, anxiety, and depression at two-time points with a five-week time interval. The results showed that the interaction between DBTP and mindfulness measured at time one could prospectively predict both anxiety and depression measured at time two. Mindfulness plays a significant moderating role in the relationship between DBTP and anxiety and depression. The data indicate that for individuals with low levels of DBTP, those with higher mindfulness experience significantly lower anxiety and depression compared to those with lower mindfulness. However, as DBTP increases, anxiety and depression levels in the high mindfulness group rise significantly, ultimately converging with those observed in the low mindfulness group. This indicates that while high mindfulness offers buffering effects against anxiety and depression, these effects diminish under increased DBTP.
Citation - WoS: 8
Citation - Scopus: 10
Attachment Anxiety Benefits From Security Priming: Evidence From Working Memory Performance
(Public Library Science, 2018) Gökçe, Ahu; Harma, Mehmet
The present study investigates the relationship between the attachment dimensions (anxious vs. avoidance) and the cognitive performance of individuals specifically whether the attachment dimensions would predict the working memory (WM) performance. In the n-back task reflecting the WM capacity both attachment related and non-attachment related words were used. Participants were randomly assigned into two groups that received either the secure or the neutral subliminal priming. In the secure priming condition the aim was to induce sense of security by presenting secure attachment words prior to the n-back task performance. In neutral priming condition neutral words that did not elicit sense of security were presented. Structural equation modeling revealed divergent patterns for attachment anxiety and avoidance dimensions under the different priming conditions. In neutral priming condition WM performance declined in terms of capacity in the n-back task for individuals who rated higher levels of attachment anxiety. However in the secure priming condition WM performance was boosted in the n-back task for individuals who rated higher levels of attachment anxiety. In other words the subliminal priming of the security led to increased WM capacity of individuals who rated higher levels of attachment anxiety. This effect however was not observed for higher levels of attachment avoidance. Results are discussed along the lines of hyperactivation and deactivation strategies of the attachment system.
Citation - WoS: 24
Citation - Scopus: 24
The Availability of Abortion at State Hospitals in Turkey: a National Study
(Elsevier, 2017) O'Neil, Mary Lou
Introduction: Abortion in Turkey has been legal since 1983 and remains so today. Despite this in 2012 the Prime Minister declared that in his opinion abortion was murder. Since then there has been growing evidence that abortion access particularly in state hospitals is being restricted although no new legislation has been offered. Objectives: The study aimed to determine the number of state hospitals in Turkey that provide abortions. Study design: The study employed a telephone survey in 2015-2016 where 431 state hospitals were contacted and asked a set of questions by a mystery patient. If possible information was obtained directly from the obstetrics/gynecology department. I removed specialist hospitals from the data set and the remaining data were analyzed for frequency and cross-tabulations were performed. Results: Only 7.8% of state hospitals provide abortion services without regard to reason which is provided for by the current law while 78% provide abortions when there is a medical necessity. Of the 58 teaching and research hospitals in Turkey 9 (15.5%) provide abortion care without restriction to reason 38 (65.5%) will do the procedure if there is a medical necessity and 11 (11.4%) of these hospitals refuse to provide abortion services under any circumstances. There are two regions encompassing 1.5 million women of childbearing age where no state hospital provides for abortion without restriction as to reason. Conclusion: The vast majority of state hospitals only provide abortions in the narrow context of a medical necessity and thus are not implementing the law to its full extent. It is clear that although no new legislation restricting abortion has been enacted state hospitals are reducing the provision of abortion services without restriction as to reason. Implications: This is the only nationwide study to focus on abortion provision at state hospitals. (C) 2017 Elsevier Inc. All rights reserved.
Citation - Scopus: 1
Background Tv and Infant-Family Interactions: Insights From Home Observations
(Wiley, 2024) Uzundag, Berna A.; Koskulu-Sancar, Suemeyye; Kuntay, Aylin C.
Background television has been found to negatively impact children's language development and self-regulatory skills, possibly due to decreased parent-child interactions. Most of the research on the relationship between background TV and caregiver-child interactions has been conducted in laboratory settings. In the current study, we conducted home observations and investigated whether infants engage in fewer interactions with family members in homes where background TV is more prevalent. We observed 32 infants at the ages of 8, 10, and 18 months in their home environments, coding for dyadic interactions (e.g., parent talking to and/or engaging with the child), triadic interactions (e.g., parent and infant play with a toy together), and infants' individual activities. Our findings revealed that background TV was negatively associated with the time infants spent in triadic interactions, positively associated with time spent engaging in individual activities, and not significantly related to the time spent in dyadic interactions. Apart from the relationship between background TV and individual activity time at 8 months, these associations remained significant even after accounting for families' socioeconomic status. These findings imply a correlation between background TV exposure and caregiver-infant-object interactions, warranting a longitudinal analysis with larger sample sizes.
Citation - WoS: 15
Citation - Scopus: 17
Biomarkers of Secondhand Smoke Exposure in Waterpipe Tobacco Venue Employees in Istanbul Moscow and Cairo
(Oxford University Press, 2018) Moon, Katherine A.; Rule, Ana M.; Magid, Hoda; Ferguson, Jacqueline; Susan, Jolie; Sun, Zhuolu; Torrey, Christine; Abubaker, Salahaddin; Levshin, Vladimir; Çarkoğlu, Aslı; Radwan, Ghada Nasr; El-Rabbat, Maha; Cohen, Joanna E.; Strickland, Paul; Breysse, Patrick N.; Navas-Acien, Ana
Background: Most smoke-free legislation to reduce secondhand smoke (SHS) exposure exempts waterpipe (hookah) smoking venues. Few studies have examined SHS exposure in waterpipe venues and their employees. Methods: We surveyed 276 employees of 46 waterpipe tobacco venues in Istanbul Moscow and Cairo. We interviewed venue managers and employees and collected biological samples from employees to measure exhaled carbon monoxide (CO) hair nicotine saliva cotinine urine cotinine urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and urine 1-hydroxypyrene glucuronide (1-OHPG). We estimated adjusted geometric mean ratios (GMR) of each SHS biomarker by employee characteristics and indoor air SHS measures. Results: There were 73 nonsmoking employees and 203 current smokers of cigarettes or waterpipe. In nonsmokers the median (interquartile) range concentrations of SHS biomarkers were 1.1 (0.2 40.9) mu g/g creatinine urine cotinine 5.5 (2 15) ng/mL saliva cotinine 0.95 (0.36 5.02) ng/mg hair nicotine 1.48 (0.98 3.97) pg/mg creatinine urine NNAL 0.54 (0.25 0.97) pmol/mg creatinine urine 1-OHPG and 1.67 (1.33 2.33) ppm exhaled CO. An 8-hour increase in work hours was associated with higher urine cotinine (GMR: 1.68 95% CI: 1.20 2.37) and hair nicotine (GMR: 1.22 95% CI: 1.05 1.43). Lighting waterpipes was associated with higher saliva cotinine (GMR: 2.83 95% CI: 1.05 7.62). Conclusions: Nonsmoking employees of waterpipe tobacco venues were exposed to high levels of SHS including measurable levels of carcinogenic biomarkers (tobacco-specific nitrosamines and PAHs).
Citation - WoS: 8
Citation - Scopus: 10
Bridging the Chemical Profiles and Biological Effects of Spathodea Campanulata Extracts: a New Contribution on the Road From Natural Treasure To Pharmacy Shelves
(Mdpi, 2022) Swiatek, Lukasz; Sieniawska, Elwira; Sinan, Kouadio Ibrahime; Zengin, Gokhan; Uba, Abdullahi Ibrahim; Bene, Kouadio; Maciejewska-Turska, Magdalena
Spathodea campanulata is an important medicinal plant with traditional uses in the tropical zone. In the current work, we aimed to determine the chemical profiles and biological effects of extracts (methanolic and infusion (water)) from the leaves and stem bark of S. campanulata. The chemical components of the tested extracts were identified using LC-ESI-QTOF-MS. Biological effects were tested in terms of antioxidant (radical scavenging, reducing power, and metal chelating), enzyme inhibitory (cholinesterase, amylase, glucosidase, and tyrosinase), antineoplastic, and antiviral activities. Fifty-seven components were identified in the tested extracts, including iridoids, flavonoids, and phenolic acids as the main constituents. In general, the leaves-MeOH extract was the most active in the antioxidant assays (DPPH, ABTS, CUPRAC, FRAP, metal chelating, and phosphomolybdenum). Antineoplastic effects were tested in normal (VERO cell line) and cancer cell lines (FaDu, HeLa, and RKO). The leaf infusion, as well as the extracts obtained from stem bark, showed antineoplastic activity (CC50 119.03-222.07 mu g/mL). Antiviral effects were tested against HHV-1 and CVB3, and the leaf methanolic extract (500 mu g/mL) exerted antiviral activity towards HHV-1, inhibiting the viral-induced cytopathic effect and reducing the viral infectious titre by 5.11 log and viral load by 1.45 log. In addition, molecular docking was performed to understand the interactions between selected chemical components and viral targets (HSV-1 DNA polymerase, HSV-1 protease, and HSV-1 thymidine kinase). The results presented suggest that S. campanulata may be a bright spot in moving from natural sources to industrial applications, including novel drugs, cosmeceuticals, and nutraceuticals.
Can Reflection Mitigate Covid-19 Vaccine Conspiracy Beliefs and Hesitancy
(Routledge, 2025) Bayrak, F.; Kayatepe, E.; Özman, N.; Yilmaz, O.; Isler, O.; Saribay, S.A.
Objective design: Periods of social turmoil, such as the COVID-19 pandemic, tend to amplify conspiracy beliefs, evidenced by increased vaccine hesitancy. Despite this trend, effective interventions targeting vaccine-related conspiracy beliefs remain scarce, partly due to underexplored cognitive processes. Three competing theoretical accounts offer differing predictions about the role of reflective thinking in supporting conspiracy beliefs: the Motivated Reasoning Account suggests reflection strengthens commitment to pre-existing attitudes; the Reflective Reasoning Account posits that reflection enhances belief accuracy; and the Reflective Doubt Account proposes reflection fosters general scepticism. Main outcome measures: Utilising open science practices and a validated technique to activate reflection, we conducted an experimental investigation with a diverse sample (N = 1483) segmented by vaccine attitudes. We investigated the impact of reflection on specific and generic COVID-19 conspiracy beliefs and vaccine-support behaviours across pro-vaccine, neutral, and vaccine-hesitant groups, while examining the moderating effects of scientific literacy, intellectual humility, and actively open-minded thinking. Results: The confirmatory analysis provided no direct support for the theoretical predictions. However, findings indicated that intellectual humility significantly moderated the effect of reflection, enhancing vaccine-support behaviour among participants with high intellectual humility, highlighting the complex interplay of cognitive style and prior attitudes in shaping responses to conspiracy beliefs and vaccine-support actions. Conclusion: The study highlights that while reflective thinking alone did not directly influence vaccine support behavior, its positive effect emerged among individuals with higher intellectual humility, emphasizing the importance of individual differences in shaping belief-related outcomes. © 2025 Informa UK Limited, trading as Taylor & Francis Group.
Citation - WoS: 17
Citation - Scopus: 16
Cation Effect on Slow Release From Alginate Beads: a Fluorescence Study
(Springer/Plenum Publishers, 2014) Kaygusuz, Hakan; Erim, F. Bedia; Pekcan, Önder; Evingür, Gülşen Akin
In this study spherical alginate beads containing pyranine (P-y) as a fluorescence probe were prepared by ionotropic gelation of a sodium alginate solution. The steady state fluorescence technique was used to study pyranine release from the alginate beads crosslinked with calcium barium and aluminum ions respectively. The slow release of P-y was observed with the time drive mode of the spectrophotometer at 512 nm. Fluorescence emission intensity (I-p) from P-y was monitored during the release process and the encapsulation efficiency (EE) of pyranine from the alginate beads was calculated. The Fickian Diffusion model was used to measure the release coefficients D-sl. It was seen that the slow release coefficients of pyranine from the alginate beads crosslinked with Ca2+ Ba2+ and Al3+ ions increased in the following order: D-sl (Al3+)> D-sl (Ca2+)> D-sl (Ba2+). In contrast the initial amount of pyranine and EE into the beads showed the reverse behavior.
Citation - Scopus: 1
Children's Questions and Teachers' Responses About Covid-19 in Türkiye and the Us
(Public Library Science, 2024) Unlutabak, Burcu; Trujillo Hernandez, Graciela; Velioglu, Ilayda; Menendez, David; Rosengren, Karl S.
Question-asking is a crucial tool for acquiring information about unseen entities, such as viruses; thus, examining children's questions within the context of COVID-19 is particularly important for understanding children's learning about the coronavirus. The study examined 3-12-year-old children's questions and teachers' responses about the COVID-19 pandemic in T & uuml;rkiye, a non-Western developing context, and the United States, a Western cultural context. A total of 119 teachers from T & uuml;rkiye and 95 teachers from the US participated in the study. Teachers completed an online survey consisting of a demographic form and a questionnaire asking them to report three questions about COVID-19 asked by children in their classrooms and their responses to these questions. We analyzed children's questions and teachers' responses for their type and content and examined demographic factors associated with children's questions and teachers' responses. Consistent with the literature, children from T & uuml;rkiye asked fewer explanation-seeking (i.e., why/how) questions than children from the United States. Children asked questions about viruses and precautions. Teachers responded to children's questions realistically in both countries. The findings have important implications for how children gain knowledge from teachers when discussing health, disease, and virus topics in two countries.
Citation - WoS: 33
Citation - Scopus: 33
Cis-Cyclopropylamines as Mechanism-Based Inhibitors of Monoamine Oxidases
(Wiley-Blackwell, 2015) Malcomson, Thomas; 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.
Citation - WoS: 25
Citation - Scopus: 29
Collective Remembering and Future Forecasting During the Covid-19 Pandemic: How the Impact of Covid-19 Affected the Themes and Phenomenology of Global and National Memories Across 15 Countries
(Springer, 2023) Oner, Sezin; Watson, Lynn Ann; Adiguzel, Zeynep; Ergen, Irem; Bilgin, Ezgi; Curci, Antonietta; Cole, Scott
The COVID-19 pandemic created a unique set of circumstances in which to investigate collective memory and future simulations of events reported during the onset of a potentially historic event. Between early April and late June 2020, we asked over 4,000 individuals from 15 countries across four continents to report on remarkable (a) national and (b) global events that (i) had happened since the first cases of COVID-19 were reported, and (ii) they expected to happen in the future. Whereas themes of infections, lockdown, and politics dominated global and national past events in most countries, themes of economy, a second wave, and lockdown dominated future events. The themes and phenomenological characteristics of the events differed based on contextual group factors. First, across all conditions, the event themes differed to a small yet significant degree depending on the severity of the pandemic and stringency of governmental response at the national level. Second, participants reported national events as less negative and more vivid than global events, and group differences in emotional valence were largest for future events. This research demonstrates that even during the early stages of the pandemic, themes relating to its onset and course were shared across many countries, thus providing preliminary evidence for the emergence of collective memories of this event as it was occurring. Current findings provide a profile of past and future collective events from the early stages of the ongoing pandemic, and factors accounting for the consistencies and differences in event representations across 15 countries are discussed.
Citation - WoS: 50
Citation - Scopus: 59
A Computational Study on the Amine-Oxidation Mechanism of Monoamine Oxidase: Insight Into the Polar Nucleophilic Mechanism
(Royal Soc Chemistry, 2006) Sağ Erdem, Safiye; Karahan, Özlem; Yıldız, İbrahim; Yelekçi, Kemal
The proposed polar nucleophilic mechanism of MAO was investigated using quantum chemical calculations employing the semi-empirical PM3 method. In order to mimic the reaction at the enzyme's active site the reactions between the flavin and the p-substituted benzylamine substrate analogs were modeled. Activation energies and rate constants of all the reactions were calculated and compared with the published experimental data. The results showed that electron-withdrawing groups at the para position of benzylamine increase the reaction rate. A good correlation between the log of the calculated rate constants and the electronic parameter (sigma) of the substituent was obtained. These results agree with the previous kinetic experiments on the effect of p-substituents on the reduction of MAO-A by benzylamine analogs. In addition the calculated rate constants showed a correlation with the rate of reduction of the flavin in MAO-A. In order to verify the results obtained from the PM3 method single-point B3LYP/6-31G*//PM3 calculations were performed. These results demonstrated a strong reduction in the activation energy for the reaction of benzylamine derivatives having electron-withdrawing substituents which is in agreement with the PM3 calculations and the previous experimental QSAR study. PM3 and B3LYP/6-31G* energy surfaces were obtained for the overall reaction of benzylamine with flavin. Results suggest that PM3 is a reasonable method for studying this kind of reaction. These theoretical findings support the proposed polar nucleophilic mechanism for MAO-A.

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