PubMed İndeksli Yayınlar Koleksiyonu
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Article Citation - WoS: 8Citation - Scopus: 9A it-Electron Rich Cage via the Friedel-Crafts Reaction(Amer Chemical Soc, 2022) Zhu, Dingsheng; Sun, Bin; Tong, Lu; Wu, Yating; Cetin, Mustafa; Li, HaoA prism-shaped cage was obtained via the Friedel-Crafts reaction in a 2:3 mixture of trisfuryl and bis-isopropenyl precursors, in a remarkable yield of 40% considering six C-C bonds formed in a one-pot manner. The cage contains two pi-electron rich trisfuryl platforms bridged in a face-to-face manner with three p-xylylene linkers. Therefore, it enables accommodation of pi-electron poor guests with complementary size, including biscationic viologen.Article Citation - WoS: 1The association of HLA-DRB1 alleles and MBL2 gene variant in pediatric acute lymphoblastic leukemia patients(Elsevier, 2024) Oguz, Rustu; Ciftci, Hayriye Senturk; Gokce, Muge; Ogret, Yeliz; Karadeniz, Sedat; Pehlivan, Sacide; Ayd, FilizIntroduction: Epidemio logic studies on pediatric acute lymphoblastic leukemias (ALL) have been conducted to evaluate the possible risk factors including genetic, infectious and environmental factors with the objective of idenfying the etiology. Mannose-binding lectin 2 (MBL2) plays an important role in first-line immune defense. HLA DRB1 alleles play a role in presentation of peptides to T cells and in activation of the adaptive immune response. Objective: In our study, we aimed to investigate both the MBL2 gene variant and HLA-DRB1 alleles in pediatric ALL patients. Materials: In this study, 86 high-risk ALL patients and 100 controls were included. Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (PCR-RFLP) and PCRsequence specific primer (SSP) methods were used for detection of polymorphism of the MBL2 and HLA-DRB1 alleles, respectively. Results: The frequency of the MBL2 AB genotype was lower in female ALL patients, compared to male ALL patients (p = 0.034). An association was found between the MBL2 BB genotype and DRB1*07 and among patients with the MBL2 BB genotype; those who also carried the DRB1*07 and *04 alleles were significantly higher than those without the DRB1*07 and *04 alleles. (p = 0.048, p = 0.022, respectively). Conclusion: This is the first study suggesting that the MBL2 BB genotype in association with the DRB1*07 or co-inheritance of the HLA-DRB1*04 and HLA DRB1*07 may have an impact on the etiopathogenesis of the disease. (c) 2023 Associa & ccedil;& atilde;o Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Espa & ntilde;a, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Article Citation - WoS: 3Relationship between dyslipidemia C-Reactive Protein and serological evidence of chlamydia pneumoniae in Turkish patients with coronary artery diseases(Luigi Ponzio E Figlio, 2004) Türkoğlu, Celalettin; Sönmez, Emine; Aydınlı, AydınRelationship between dyslipidemia C-Reactive Protein (CRP) and serological evidence of Chlamydia pneumoniae was investigated in a Turkish population with coronary artery disease. This prospective randomized blinded study was carried out in Florence Nightingale Hospital which is affiliated to Kadir Has University Medical Faculty. Thirty-two patients with acute coronary artery diseases (ACAD) 32 patients with chronic coronary artery diseases (CCAD) and 26 healthy controls (HC) were included in the study We detected serum concentrations of C. pneumoniae IgG IgA and IgM by ELISA method. We measured total cholesterol trigliseride LDL and HDL- cholesterol levels to determine dyslipidemia which was defined as total cholesterol >200 mg/dL trigliserid > 150 Mg/dL LDL >130 mg/dL HDL <45 mg/dL. CRP levels were also measured. Seropositivity to C. pneumoniae IgG was 84.3% 100% and 65.3%Article Citation - WoS: 34Citation - Scopus: 38Compliance With Smoke-Free Legislation Within Public Buildings: a Cross-Sectional Study in Turkey(World Health Organization, 2016) Navas-Acien, Ana; Çarkoğlu, Aslı; Ergör, Gül; Hayran, Mutlu; Ergüder, Toker; Kaplan, Bekir; Susan, Jolie; Magid, Hoda; Pollak, Jonathan; Cohen, Joanna E.ObjectiveTo investigate public compliance with legislation to prohibit smoking within public buildings and the extent of tobacco smoking in outdoor areas in Turkey. Methods Using a standardized observation protocol we determined whether smoking occurred and whether ashtrays cigarette butts and/or no-smoking signs were present in a random selection of 884 public venues in 12 cities in Turkey. We visited indoor and outdoor locations in bars/nightclubs cafes government buildings hospitals restaurants schools shopping malls traditional coffee houses and universities. We used logistic regression models to determine the association between the presence of ashtrays or the absence of no-smoking signs and the presence of individuals smoking or cigarette butts. Findings Most venues had no-smoking signs (629/884). We observed at least one person smoking in 145 venues most frequently observed in bars/nightclubs (63/79) hospital dining areas (18/79) traditional coffee houses (27/120) and government-building dining areas (5/23). For 538 venues we observed outdoor smoking close to public buildings. The presence of ashtrays was positively associated with indoor smoking and cigarette butts adjusted odds ratio aOR: 315.9Article Citation - WoS: 1Citation - Scopus: 1Quantum Models of Consciousness From a Quantum Information Science Perspective(Mdpi, 2025) Gassab, Lea; Pusuluk, Onur; Cattaneo, Marco; Muestecaplioglu, Ozgur E.This perspective explores various quantum models of consciousness from the viewpoint of quantum information science, offering potential ideas and insights. The models under consideration can be categorized into three distinct groups based on the level at which quantum mechanics might operate within the brain: those suggesting that consciousness arises from electron delocalization within microtubules inside neurons, those proposing it emerges from the electromagnetic field surrounding the entire neural network, and those positing it originates from the interactions between individual neurons governed by neurotransmitter molecules. Our focus is particularly on the Posner model of cognition, for which we provide preliminary calculations on the preservation of entanglement of phosphate molecules within the geometric structure of Posner clusters. These findings provide valuable insights into how quantum information theory can enhance our understanding of brain functions.Article Citation - WoS: 21Citation - Scopus: 22Impacts of Covid-19 on Changing Patterns of Household Food Consumption: an Intercultural Study of Three Countries(Elsevier, 2021) Kartari, Asker; Ozen, Asli Emine; Correia, Antonia; Wen, Jun; Kozak, MetinIn light of COVID-19's effects on individuals' social, economic, political, and psychological values, this paper aims to investigate the pandemic's role in possible changes to people's food consumption and meal habits in three countries, namely China, Portugal, and Turkey. The sample includes individuals from the three countries, exploratory factor analysis and non-parametric tests were used to test the differences. Results suggest that coronavirus has played a strong part in altering households' food consumption and meal habits within these countries. The pandemic has particularly led to greater consumption of fresh fruits and vegetables and spending more time eating meals at home. Portugal appears to be consuming more seafood, bread, and butter whereas China features higher consumption of rice and meat products; Turkey is consuming more meat and eggs. The study closes with a set of recommendations for the society and future research.Article Citation - WoS: 2Citation - Scopus: 2Altered 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 DemetThe 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.Editorial Citation - WoS: 1A Low-Cost Wireless Miniaturized Device for Food Spoilage Monitoring(Nature Portfolio, 2023) Istif, Emin; Beker, Levent[Abstract Not Available]Article Citation - Scopus: 17Off-Pump Coronary Artery Bypass Grafting With Use of the Octopus 2 Stabilization System.(2000) Akpinar,B.; Güden,M.; Sagbas,E.; Sanisoglu,I.; Aytekin,V.; Bayindir,O.BACKGROUND: The treatment of coronary artery disease has evolved rapidly over the last two decades. The gold standard of surgical revascularization, the on-pump coronary artery bypass graft, has been challenged by the development of percutaneous transluminal coronary angioplasty. Our experience with the alternative of the off-pump ("beating heart") coronary artery bypass (OPCAB) technique during a period of 18 months suggests that OPCAB avoids the complications of cardiopulmonary bypass and offers patients the benefit of long-term graft patency that greatly exceeds that of current endovascular technologies. METHODS: The early results of 126 OPCAB procedures performed through a medial sternotomy incision during a period of 18 months were evaluated. There were 80 male and 46 female patients, with a mean age of 69 +/- 4.3 years. Emergency cases and reoperations were not included. A total of 268 anastomoses were performed, with a mean number of 2.12 anastomoses per patient. Conduits used, with their percentage of use, were: left internal thoracic artery (LITA) (100%), right internal thoracic artery (11.1%), greater saphenous vein (84%), and radial artery (31%). In 72% of the cases, off-pump surgery was chosen because of patient risk factors such as atherosclerotic aortic disease, previous cerebrovascular accident or carotid artery disease, renal dysfunction, malignancy or poor left ventricular function. RESULTS: There was no operative mortality. One-month postoperative mortality was three patients (2.3%). Two died because of mesenteric ischemia, and the other death was due to cardiac failure. Seventy-one patients had a control angiogram before discharge. The patency of LITA anastomosis was 100% while overall patency rate was 95%. In 43 patients for whom an angiogram could not be performed, a Thallum 201 stress test was performed three months postoperatively. Thirty-eight patients had a normal test while five patients showed signs of ischemia. These patients had a control angiogram: in four patients anastomoses were patent, but in one patient there was a severe narrowing of a venous anastomosis to the distal right coronary artery (RCA) which was corrected with angioplasty. In the whole series eight patients (6.3%) refused to have any control examination. CONCLUSIONS: Our early results suggest that off-pump CABG with Octopus 2 (Medtronic, Inc., Minneapolis, MN) can be a good alternative in high risk patients who need multiple vessel revascularization.Article Citation - WoS: 105Citation - Scopus: 179The Applications of Machine Learning Techniques in Medical Data Processing Based on Distributed Computing and the Internet of Things(Elsevier Ireland Ltd, 2023) Aminizadeh, Sarina; Heidari, Arash; Toumaj, Shiva; Darbandi, Mehdi; Navimipour, Nima Jafari; Rezaei, Mahsa; Talebi, SamiraMedical data processing has grown into a prominent topic in the latest decades with the primary goal of maintaining patient data via new information technologies, including the Internet of Things (IoT) and sensor technologies, which generate patient indexes in hospital data networks. Innovations like distributed computing, Machine Learning (ML), blockchain, chatbots, wearables, and pattern recognition can adequately enable the collection and processing of medical data for decision-making in the healthcare era. Particularly, to assist experts in the disease diagnostic process, distributed computing is beneficial by digesting huge volumes of data swiftly and producing personalized smart suggestions. On the other side, the current globe is confronting an outbreak of COVID-19, so an early diagnosis technique is crucial to lowering the fatality rate. ML systems are beneficial in aiding radiologists in examining the incredible amount of medical images. Nevertheless, they demand a huge quantity of training data that must be unified for processing. Hence, developing Deep Learning (DL) confronts multiple issues, such as conventional data collection, quality assurance, knowledge exchange, privacy preservation, administrative laws, and ethical considerations. In this research, we intend to convey an inclusive analysis of the most recent studies in distributed computing platform applications based on five categorized platforms, including cloud computing, edge, fog, IoT, and hybrid platforms. So, we evaluated 27 articles regarding the usage of the proposed framework, deployed methods, and applications, noting the advantages, drawbacks, and the applied dataset and screening the security mechanism and the presence of the Transfer Learning (TL) method. As a result, it was proved that most recent research (about 43%) used the IoT platform as the environment for the proposed architecture, and most of the studies (about 46%) were done in 2021. In addition, the most popular utilized DL algorithm was the Convolutional Neural Network (CNN), with a percentage of 19.4%. Hence, despite how technology changes, delivering appropriate therapy for patients is the primary aim of healthcare-associated departments. Therefore, further studies are recommended to develop more functional architectures based on DL and distributed environments and better evaluate the present healthcare data analysis models.Article Citation - WoS: 72Citation - Scopus: 77Combined Radiofrequency Modified Maze and Mitral Valve Procedure Through a Port Access Approach: Early and Mid-Term Results(Oxford University Press, 2003) Akpınar, Belhhan; Güden, Mustafa; Sağbaş, Ertan; Sanisoğlu, İlhan; Özbek, Uğur; Caynak, Barış; Bayındır, OsmanObjective: The aim of this study was to assess the feasibility and effectiveness of irrigated radiofrequency (RF) modified Maze procedure through a port access approach during mitral valve surgery and evaluate early and mid-term results. Material and method: During a 16 months time period 67 patients with chronic atrial fibrillation (AF) eligible for port access mitral valve surgery were randomly assigned to either Group A in which they underwent a combined procedure (N = 33) or Group B in which a valve procedure alone was performed (N = 34). Both groups were similar in terms of age sex valve pathology duration of AF left atrial diameter and left ventricle function (P > 0.05). Four had undergone previous operations. Results: Median follow-up was 10 months for both groups 95% CI (9.18-10.8). One patient in each group died early postoperatively (3 and 2.9%). Two patients required reoperation for bleeding one in each group (3 and 2.9%). There were two conversions to right thoracotomy. In Group A freedom from AF was 100% at the end of the operation (76% sinus 24% pacemaker) Six and twelve months freedom from AF was 87.2 and 93.6% respectively. In Group B freedom from AF at the end of operation was 41%. At the end of 6 and 12 months freedom from AF was 9.4% (P = 0.0001). One patient in Group A required a permanent pacemaker (3%). During follow-up one patient in Group A died of non-cardiac causes (3%). In Group B there were two late deaths: one cardiac (2.9%) and one neurologic (2.9%). There were no thromboembolic events detected in Group A during follow-up whereas two patients in Group B suffered this complication (6% P = 0.081). At 12 months functional capacity had improved for patients in both groups (P < 0.0001). Conclusion: The combination of mitral valve surgery and irrigated RF Maze procedure was safe and efficient through a port access approach. There were no procedure related complications like esophageal or coronary artery injury. Early and mid-term results were favourable with 93.6% of patients free of AF at 1 year in comparison to the 9.4% of the control group. The data is not sufficient to reach any conclusions in terms of thromboembolic rates despite favourable results for the RF Maze group. Nevertheless in terms of feasibilty sinus rhythm restoration and overall outcome early results are encouraging and we advocate the use of the combined procedure through a port access approach. (C) 2003 Elsevier Science B.V. All rights reserved.Article Citation - WoS: 8Citation - Scopus: 10Hb-Egf Promotes Progenitor Cell Proliferation and Sensory Neuron Regeneration in the Zebrafish Olfactory Epithelium(Wiley, 2024) Sireci, Siran; Kocagoz, Yigit; Alkiraz, Aysu Sevval; Guler, Kardelen; Dokuzluoglu, Zeynep; Balcioglu, Ecem; Fuss, Stefan HerbertMaintenance and regeneration of the zebrafish olfactory epithelium (OE) are supported by two distinct progenitor cell populations that occupy spatially discrete stem cell niches and respond to different tissue conditions. Globose basal cells (GBCs) reside at the inner and peripheral margins of the sensory OE and are constitutively active to replace sporadically dying olfactory sensory neurons (OSNs). In contrast, horizontal basal cells (HBCs) are uniformly distributed across the sensory tissue and are selectively activated by acute injury conditions. Here we show that expression of the heparin-binding epidermal growth factor-like growth factor (HB-EGF) is strongly and transiently upregulated in response to OE injury and signals through the EGF receptor (EGFR), which is expressed by HBCs. Exogenous stimulation of the OE with recombinant HB-EGF promotes HBC expansion and OSN neurogenesis in a pattern that resembles the tissue response to injury. In contrast, pharmacological inhibition of HB-EGF membrane shedding, HB-EGF availability, and EGFR signaling strongly attenuate or delay injury-induced HBC activity and OSN restoration without affecting maintenance neurogenesis by GBCs. Thus, HB-EGF/EGFR signaling appears to be a critical component of the signaling network that controls HBC activity and, consequently, repair neurogenesis in the zebrafish OE.Article Citation - WoS: 17Citation - Scopus: 16Investigation of Allosteric Coupling in Human Beta(2)-Adrenergic Receptor in the Presence of Intracellular Loop 3(BMC, 2016) Özgür, Canan; Doruker, Pemra; Akten, Ebru DemetBackground: This study investigates the allosteric coupling that exists between the intra- and extracellular parts of human beta(2)-adrenergic receptor (beta(2)-AR) in the presence of the intracellular loop 3 (ICL3) which is missing in all crystallographic experiments and most of the simulation studies reported so far. Our recent 1 mu s long MD run has revealed a transition to the so-called very inactive state of the receptor in which ICL3 packed under the G protein's binding cavity and completely blocked its accessibility to G protein. Simultaneously an outward tilt of transmembrane helix 5 (TM5) caused an expansion of the extracellular ligand-binding site. In the current study we performed independent runs with a total duration of 4 mu s to further investigate the very inactive state with packed ICL3 and the allosteric coupling event (three unrestrained runs and five runs with bond restraints at the ligand-binding site). Results: In all three independent unrestrained runs (each 500 ns long) ICL3 preserved its initially packed/closed conformation within the studied time frame suggesting an inhibition of the receptor's activity. Specific bond restraints were later imposed between some key residues at the ligand-binding site which have been experimentally determined to interact with the ligand. Restraining the binding site region to an open state facilitated ICL3 closure whereas a relatively constrained/closed binding site hindered ICL3 packing. However the reverse operation i.e. opening of the packed ICL3 could not be realized by restraining the binding site region to a closed state. Thus any attempt failed to free the ICL3 from its locked state due to the presence of persistent hydrogen bonds. Conclusions: Overall our simulations indicated that starting with very inactive states the receptor stayed almost irreversibly inhibited which in turn decreased the overall mobility of the receptor. Bond restraints which represented the geometric restrictions caused by ligands of various sizes when bound at the ligand-binding site induced the expected conformational changes in TM5 TM6 and consequently ICL3. Still once ICL3 was packed the allosteric coupling became ineffective due to strong hydrogen bonds connecting ICL3 to the core of the receptor.Article Citation - WoS: 17Citation - Scopus: 20Identification of Potential Inhibitors of Human Methionine Aminopeptidase (type Ii) for Cancer Therapy: Structure-Based Virtual Screening, Admet Prediction and Molecular Dynamics Studies(Elsevier, 2020) Weako, Jackson; Uba, Abdullahi Ibrahim; Keskin, Özlem; Gürsoy, Attila; Yelekçi, KemalMethionine Aminopeptidases MetAPs are divalent-cofactor dependent enzymes that are responsible for the cleavage of the initiator Methionine from the nascent polypeptides. MetAPs are classified into two isoforms: namely, MetAP1 and MetAP2. Several studies have revealed that MetAP2 is upregulated in various cancers, and its inhibition has shown to suppress abnormal or excessive blood vessel formation and tumor growth in model organisms. Clinical studies show that the natural product fumagillin, and its analogs are potential inhibitors of MetAP2. However, due to their poor pharmacokinetic properties and neurotoxicities in clinical studies, their further developments have received a great setback. Here, we apply structure-based virtual screening and molecular dynamics methods to identify a new class of potential inhibitors for MetAP2. We screened Otava's Chemical Library, which consists of about 3 200 000 tangible-chemical compounds, and meticulously selected the top 10 of these compounds based on their inhibitory potentials against MetAP2. The top hit compounds subjected to ADMET predictor using 3 independent ADMET prediction programs, were found to be drug-like. To examine the stability of ligand binding mode, and efficacy, the unbound form of MetAP2, its complexes with fumagillin, spiroepoxytriazole, and the best promising compounds compound-3369841 and compound-3368818 were submitted to 100 ns molecular dynamics simulation. Like fumagillin, spiroepoxytriazole, and both compound-3369841 and compound-3368818 showed stable binding mode over time during the simulations. Taken together, these uninherited-fumagillin compounds may serve as new class of inhibitors or provide scaffolds for further optimization towards the design of more potent MetAP2 inhibitors -development of such inhibitors would be essential strategy against various cancer types.Article Citation - WoS: 10Citation - Scopus: 11Polymorphisms at the Ligand Binding Site of the Vitamin D Receptor Gene and Osteomalacia(Hindawi Ltd, 2005) Ak, Duygu Gezen; Kahraman, Hakkı; Dursun, Erdinç; Duman, Belgin Süsleyici; Erensoy, Nevin; Alagöl, Faruk; Tanakol, Refik; Yilmazer, SelmaVitamin D receptor (VDR) gene polymorphisms have been suggested as possible determinants of bone mineral density (BMD) and calcium metabolism. In this study our aim was to determine whether there is an association between VDR gene polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium phosphorus ALP PTH 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p=0.08). Also no association between biochemical data and VDR gene polymorphisms was observed.Article Citation - WoS: 4Association of Lipoprotein(a) Concentration and Apo(a) Isoform Size With Restenosis After Percutaneous Transluminal Coronary Angioplasty(Springer Verlag, 2000) Sırıkcı, Onder; Aytekin, Vedat; Demiroglu, I. C. C.; Demiroğlu, Cemşid; Marcovina, S.M.Lp(a) is a unique class of lipoprotein particles that exhibits a considerable size heterogeneity resulting from the size polymorphism of apo(a) its unique protein component. An elevated level of Lp(a) in plasma has been proposed to be a risk factor for premature development of coronary artery disease. To evaluate the relationship between Lp(a) concentration and apo(a) isoform size with restenosis after percutaneous transluminal coronary angioplasty Lp(a) levels and apo(a) phenotypes were determined in 204 patients who underwent a successful coronary angioplasty procedure and stent implantation. The patients were followed with clinical examinations and exercise tests at 1 3 and 6 months and a control coronary angiography was performed after 6 months to evaluate restenosis. Lp(a) levels were determined with an ELISA that is insensitive to the size heterogeneity of Lp(a) and the apo(a) isoforms were determined by a high-resolution agarose gel electrophoresis method followed by immunoblotting with a specific monoclonal antibody. Of the 146 patients who underwent angiographic evaluation 57 (39%) had restenosis whereas 89 (61%) did not. Lp(a) levels and the distribution of the expressed apo(a) phenotypes were compared in these two groups of patients. Although the mean and median Lp(a) levels were higher in the restenosed group the difference was not statistically significant. However a significant difference in Lp(a) values was found in women (P=0.043) even though because of the small number of women in the study (n=35) no sound conclusions can be reached on the predictive role of Lp(a) in restenosis. There also was no difference in the distribution of apo(a) phenotypes between the two groups. Because of their wide distribution Lp(a) values and apo(a) isoforms do not seem to be a useful indicator of risk of restenosis after percutaneous transluminal coronary angioplasty in our study cohort.Article Citation - WoS: 10Citation - Scopus: 10Ligand-Binding Affinity of Alternative Conformers of Human Beta(2)-Adrenergic Receptor in the Presence of Intracellular Loop 3 (icl3) and Their Potential Use in Virtual Screening Studies(Wiley, 2019) Dilcan, Gonca; Doruker, Pemra; Akten, Ebru DemetThis study investigates the structural distinctiveness of orthosteric ligand-binding sites of several human beta(2) adrenergic receptor (beta(2)-AR) conformations that have been obtained from a set of independent molecular dynamics (MD) simulations in the presence of intracellular loop 3 (ICL3). A docking protocol was established in order to classify each receptor conformation via its binding affinity to selected ligands with known efficacy. This work's main goal was to reveal many subtle features of the ligand-binding site presenting alternative conformations which might be considered as either active- or inactive-like but mostly specific for that ligand. Agonists inverse agonists and antagonists were docked to each MD conformer with distinct binding pockets using different docking tools and scoring functions. Mostly favored receptor conformation persistently observed in all docking/scoring evaluations was classified as active or inactive based on the type of ligand's biological effect. Classified MD conformers were further tested for their ability to discriminate agonists from inverse agonists/antagonists and several conformers were proposed as important targets to be used in virtual screening experiments that were often limited to a single X-ray structure.Article Citation - WoS: 3Citation - Scopus: 3The Neural Gamma(2)alpha(1)beta(2)alpha(1)beta(2) Gamma Amino Butyric Acid Ion Channel Receptor: Structural Analysis of the Effects of the Ivermectin Molecule and Disulfide Bridges(Springer, 2018) Ayan, Meral; Eşsiz, ŞebnemWhile similar to 30% of the human genome encodes membrane proteins only a handful of structures of membrane proteins have been resolved to high resolution. Here we studied the structure of a member of the Cys-loop ligand gated ion channel protein superfamily of receptors human type A gamma(2)alpha(1)beta(2)alpha(1)beta(2) gamma amino butyric acid receptor complex in a lipid bilayer environment. Studying the correlation between the structure and function of the gamma amino butyric acid receptor may enhance our understanding of the molecular basis of ion channel dysfunctions linked with epilepsy ataxia migraine schizophrenia and other neurodegenerative diseases. The structure of human gamma(2)alpha(1)beta(2)alpha(1)beta(2) has been modeled based on the X-ray structure of the Caenorhabditis elegans glutamate-gated chloride channel via homology modeling. The template provided the first inhibitory channel structure for the Cys-loop superfamily of ligand-gated ion channels. The only available template structure before this glutamate-gated chloride channel was a cation selective channel which had very low sequence identity with gamma aminobutyric acid receptor. Here our aim was to study the effect of structural corrections originating from modeling on a more reliable template structure. The homology model was analyzed for structural properties via a 100 ns molecular dynamics (MD) study. Due to the structural shifts and the removal of an open channel potentiator molecule ivermectin from the template structure helical packing changes were observed in the transmembrane segment. Namely removal of ivermectin molecule caused a closure around the Leu 9 position along the ion channel. In terms of the structural shifts there are three potential disulfide bridges between the M1 and M3 helices of the gamma(2) and 2 alpha(1) subunits in the model. The effect of these disulfide bridges was investigated via monitoring the differences in root mean square fluctuations (RMSF) of individual amino acids and principal component analysis of the MD trajectory of the two homology models-one with the disulfide bridge and one with protonated Cys residues. In all subunit types RMSF of the transmembrane domain helices are reduced in the presence of disulfide bridges. Additionally loop A loop F and loop C fluctuations were affected in the extracellular domain. In cross-correlation analysis of the trajectory the two model structures displayed different coupling in between the M2-M3 linker region protruding from the membrane and the beta 1-beta 2/D loop and cys-loop regions in the extracellular domain. Correlations of the C loop which collapses directly over the bound ligand molecule were also affected by differences in the packing of transmembrane helices. Finally more localized correlations were observed in the transmembrane helices when disulfide bridges were present in the model. The differences observed in this study suggest that dynamic coupling at the interface of extracellular and ion channel domains differs from the coupling introduced by disulfide bridges in the transmembrane region. We hope that this hypothesis will be tested experimentally in the near future.Article Citation - WoS: 1Citation - Scopus: 2Decoding cultural conflicts(Frontiers Media Sa, 2023) Kocak, Ozgecan; Puranam, Phanish; Yegin, AfsarAs pioneers of the Carnegie Perspective recognized, conflicts in organizations can exist even when incentives of all parties are aligned. These can often be traced to differences in cognitions such as beliefs and values, which are foundational components of any given culture. This paper refines the operationalization of cultural clashes by identifying differences in beliefs about causality (which actions cause which outcomes) and morality (in the broad sense of what is evaluated as desirable) as two fundamental sources of conflict. In our first study, we demonstrate empirically that participants recognize and distinguish between these two sources of conflict. In our second study, we test the hypotheses that while misalignments in either causal or moral codes increase observers' perceptions of relationship conflict, negative affect, likelihood of avoidance, and lower perceived likelihood of conflict resolution, the effects are stronger for misalignments in moral codes than misalignments in causal codes and strongest when both causal and moral codes are misaligned. We test these arguments using vignette-based experimental studies. Our findings support our hypotheses. This research has significant implications for the understanding of conflict dynamics within and beyond organizational contexts. By recognizing the pivotal role of cultural differences in shaping conflicts, organizations and decision-makers can better anticipate, manage, and potentially preempt such conflicts.Article Citation - WoS: 53Citation - Scopus: 64Synthesis of Some Novel Hydrazone and 2-Pyrazoline Derivatives: Monoamine Oxidase Inhibitory Activities and Docking Studies(Pergamon-Elsevier Science Ltd, 2014) Evranos-Aksoz, Begum; Yabanoglu-Ciftci, Samiye; Ucar, Gulberk; Yelekçi, Kemal; Ertan, RahmiyeA novel series of 2-pyrazoline and hydrazone derivatives were synthesized and investigated for their human monoamine oxidase (hMAO) inhibitory activity. All compounds inhibited the hMAO isoforms (MAO-A or MAO-B) competitively and reversibly. With the exception of 5i which was a selective MAO-B inhibitor all derivatives inhibited hMAO-A potently and selectively. According to the experimental K-i values compounds 6e and 6h exhibited the highest inhibitory activity towards the hMAO-A whereas compound 5j which carries a bromine atom at R-4 of the A ring of the pyrazoline appeared to be the most selective MAO-A inhibitor. Tested compounds were docked computationally into the active site of the hMAO-A and hMAO-B isozymes. The computationally obtained results were in good agreement with the corresponding experimental values. (C) 2014 Elsevier Ltd. All rights reserved.
