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Publication Metadata only A structural basis for restricted codon recognition mediated by 2-thiocytidine in tRNA containing a wobble position inosine(Elsevier, 2020) Vangaveti, Sweta; Cantara, William A.; Spears, Jessica L.; Murphy, Frank V.; Ranganathan, Sri V.; Sarachan, Kathryn L.; Agris, Paul F.; Department of Molecular Biology and Genetics; Demirci, Hasan; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 307350Three of six arginine codons (CGU, CGC, and CGA) are decoded by two Escherichia coli tRNA(Arg) isoacceptors. The anticodon stem and loop (ASL) domains of tRNA(Arg1) and tRNA(Arg2) both contain inosine and 2-methyladenosine modifications at positions 34 (I-34) and 37 (m(2)A(37)). tRNA(Arg1) is also modified from cytidine to 2-thiocytidine at position 32 (s(2)C(32)). The s(2)C(32) modification is known to negate wobble codon recognition of the rare CGA codon by an unknown mechanism, while still allowing decoding of CGU and CGC. Substitution of s(2)C(32) for C-32 in the Saccharomyces cerevisiae tRNA(IAU)(lle) anticodon stem and loop domain (ASL) negates wobble decoding of its synonymous A-ending codon, suggesting that this function of s(2)C at position 32 is a generalizable property. X-ray crystal structures of variously modified ASL(ICG)(Arg1) and ASL(ICG)(Arg2) constructs bound to cognate and wobble codons on the ribosome revealed the disruption of a C-32-A(38) cross-loop interaction but failed to fully explain the means by which s(2)C(32) restricts I-34 wobbling. Computational studies revealed that the adoption of a spatially broad inosine-adenosine base pair at the wobble position of the codon cannot be maintained simultaneously with the canonical ASL U-turn motif. C-32-A(38) cross-loop interactions are required for stability of the anticodon/codon interaction in the ribosomal A-site.Publication Metadata only Alteration of cell motility dynamics through collagen fiber density in photopolymerized polyethylene glycol hydrogels(Elsevier, 2020) Bayraktar, Halil; N/A; Akalın, Özge Begüm; Master Student; Graduate School of Sciences and Engineering; N/APolyethylene glycol (PEG) hydrogels that have natural fibers mimicking extracellular matrix can be used as a model to understand the role of substrate properties on cell growth and migration. Due to the dependence of cell movement to adhesion, characterization of motility is needed to prepare biocompatible substrates. We demonstrated a method to encapsulate collagen into PEG hydrogel crosslinked via photopolymerization and studied the effect of fiber density on motility dynamics. Porous hydrogel immersed into collagen solution was coated with fibers after neutralizing solution. We provided a detailed study of cell instantaneous/average speed, total displacement, persistence and angular displacement. We found that cells demonstrated a biphasic motility where a maximum speed of 17.4 mu m/h with a total distance of 215 mu m and persistence of 0.43 were obtained at 12 mg/ml collagen. High occurrence of low angular displacement observed at intermediate fiber density suggests that cells tend to move forward along hydrogels. Increased anisotropy at low density was an indication of forward and backward movement. Finally, matrix deformation was determined in the absence of fluorescent beads by tracking fiber displacement at subpixel resolution. Our findings establish a method for preparation of collagen coated hydrogels and provide an insight into cell motility dynamics.Publication Open Access An efficient framework to identify key miRNA-mRNA regulatory modules in cancer(Oxford University Press (OUP), 2020) N/A; Department of Industrial Engineering; Mokhtaridoost, Milad; Gönen, Mehmet; Faculty Member; Department of Industrial Engineering; Graduate School of Sciences and Engineering; College of Engineering; School of MedicineMotivation: micro-RNAs (miRNAs) are known as the important components of RNA silencing and post-transcriptional gene regulation, and they interact with messenger RNAs (mRNAs) either by degradation or by translational repression. miRNA alterations have a significant impact on the formation and progression of human cancers. Accordingly, it is important to establish computational methods with high predictive performance to identify cancer-specific miRNA-mRNA regulatory modules. Results: we presented a two-step framework to model miRNA-mRNA relationships and identify cancer-specific modules between miRNAs and mRNAs from their matched expression profiles of more than 9000 primary tumors. We first estimated the regulatory matrix between miRNA and mRNA expression profiles by solving multiple linear programming problems. We then formulated a unified regularized factor regression (RFR) model that simultaneously estimates the effective number of modules (i.e. latent factors) and extracts modules by decomposing regulatory matrix into two low-rank matrices. Our RFR model groups correlated miRNAs together and correlated mRNAs together, and also controls sparsity levels of both matrices. These attributes lead to interpretable results with high predictive performance. We applied our method on a very comprehensive data collection by including 32 TCGA cancer types. To find the biological relevance of our approach, we performed functional gene set enrichment and survival analyses. A large portion of the identified modules are significantly enriched in Hallmark, PID and KEGG pathways/gene sets. To validate the identified modules, we also performed literature validation as well as validation using experimentally supportedmiRTarBase database.Publication Open Access Causality, transfer entropy, and allosteric communication landscapes in proteins with harmonic interactions(Wiley, 2017) Department of Chemical and Biological Engineering; Hacısüleyman, Aysima; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; N/A; 179997A fast and approximate method of generating allosteric communication landscapes in proteins is presented by using Schreiber's entropy transfer concept in combination with the Gaussian Network Model of proteins. Predictions of the model and the allosteric communication landscapes generated show that information transfer in proteins does not necessarily take place along a single path, but an ensemble of pathways is possible. The model emphasizes that knowledge of entropy only is not sufficient for determining allosteric communication and additional information based on time delayed correlations should be introduced, which leads to the presence of causality in proteins. The model provides a simple tool for mapping entropy sink-source relations into pairs of residues. By this approach, residues that should be manipulated to control protein activity may be determined. This should be of great importance for allosteric drug design and for understanding the effects of mutations on function. The model is applied to determine allosteric communication in three proteins, Ubiquitin, Pyruvate Kinase, and the PDZ domain. Predictions are in agreement with molecular dynamics simulations and experimental evidence.Publication Open Access Cloning, expression, purification, crystallization and X-ray analysis of inositol monophosphatase from Mus musculus and Homo sapiens(Wiley, 2012) Singh, Nisha; Halliday, Amy C.; Knight, Matthew; Lowe, Edward; Churchill, Grant C.; Lack, Nathan Alan; Faculty Member; School of Medicine; 120842Inositol monophosphatase (IMPase) catalyses the hydrolysis of inositol monophosphate to inositol and is crucial in the phosphatidylinositol (PI) signalling pathway. Lithium, which is the drug of choice for bipolar disorder, inhibits IMPase at therapeutically relevant plasma concentrations. Both mouse IMPase 1 (MmIMPase 1) and human IMPase 1 (HsIMPase 1) were cloned into pRSET5a, expressed in Escherichia coli, purified and crystallized using the sitting-drop method. The structures were solved at resolutions of 2.4 and 1.7 angstrom, respectively. Comparison of MmIMPase 1 and HsIMPase 1 revealed a core r.m.s. deviation of 0.516 angstrom.Publication Metadata only Comparative molecular dynamics simulations of amphotericin B-cholesterol/ergosterol membrane channels(Elsevier, 2002) Baginski, Maciej; Borowski, Edward; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/AAmphotericin B (AmB) is a very effective anti-fungal polyene macrolide antibiotic whose usage is limited by its toxicity. Lack of a complete understanding of AmB's molecular mechanism has impeded attempts to design less toxic AmB derivatives. The antibiotic is known to interact with sterols present in the cell membrane to form ion channels that disrupt membrane function. The slightly higher affinity of AmB toward ergosterol (dominant sterol in fungal cells) than cholesterol (mammalian sterol) is regarded as the most essential factor on which antifungal chemotherapy is based. To study these differences at the molecular level, two realistic model membrane channels containing molecules of AmB, sterol (cholesterol or ergosterol), phospholipid, and water were studied by molecular dynamics (MID) simulations. Comparative analysis of the simulation data revealed that the sterol type has noticeable effect on the properties of AmB membrane channels. In addition to having a larger size, the AmB channel in the ergosterol-containing membrane has a more pronounced pattern of intermolecular hydrogen bonds. The interaction between the antibiotic and ergosterol is more specific than between the antibiotic and cholesterol. These observed differences suggest that the channel in the ergosterol-containing membrane is more stable and, due to its larger size, would have a higher ion conductance. These observations are in agreement with experiments. (C) 2002 Elsevier Science B.V. All rights reserved.Publication Metadata only Conservation of migratory species(Cell Press, 2018) Horns, Joshua J.; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 327589N/APublication Metadata only Cornerstones of biochemistry in stamps(Walter De Gruyter Gmbh, 2016) N/A; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807N/APublication Open Access Correspondence: importance of the validated serum biochemistry and hemogram parameters for rapid diagnosis and to prevent false negative results during COVID-19 pandemic(Wiley, 2020) Ulusu, Nuriye Nuray; Aydemir, Duygu; Faculty Member; PhD Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 6807; N/ACOVID-19 threatens millions of lives, especially elderly population and people with chronic diseases including diabetes, hypertension, cancer, and cardiovascular diseases. Rapid and effective diagnoses are vital for the isolation of infected people and starting treatment immediately to stop the spread of COVID-19 virus. Bioinformatics techniques such as artificial intelligence should be used for collecting the hemogram and serum biochemistry data of all COVID-19- infected people worldwide, even they do not show severe symptoms. These data may help find a biomarker that can be used in combination with the CT results for rapid and accurate diagnosis of COVID-19.Publication Metadata only COVID-19 may enhance risk of thrombosis and hemolysis in the G6PD deficient patients(Taylor & Francis Inc, 2021) Dağlıoğlu, Gülçin; Candevir, Aslıhan; Kurtaran, Behice; Bozdoğan, Sevcan Tan; İnal, Tamer Cevat; N/A; Aydemir, Duygu; Ulusu, Nuriye Nuray; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 6807COVID-19 has become a major public health problem since December, 2019 and no highly effective drug has been found until now. Numbers of infected people and deaths by COVID-19 are increasing every day worldwide, therefore self-isolation and protection are highly recommended to prevent the spread of the virus and especially to protect major risk groups such as the elderly population and people with comorbidities including diabetes, hypertension, cancer, cardiovascular diseases and metabolic syndrome. on the other hand, young people without any secondary disease have died by COVID-19 as well. In this study we compared two male patients infected by COVID-19 at the same age and one of them was diagnosed with G6PD deficiency. Both COVID-19and G6PD deficiency enhance the risk of hemolysis and thrombosis. Serum biochemistry, hemogram and immunological parameters showed that risk of hemolysis and thrombosis may increase in the G6PD deficient patient infected by COVID-19.