Browsing by Author "Sezerman, Ugur"

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A possible founder mutation in FZD6 gene in a Turkish family with autosomal recessive nail dysplasia
(BMC, 2019-01-01) Saygi, Ceren; Alanay, Yasemin; Sezerman, Ugur; Yenenler, Asli; Ozoren, Nesrin
BackgroundAutosomal recessive nail dysplasia is characterized by thick and hard nails with a very slow growth on the hands and feet. Mutations in FZD6 gene were found to be associated with autosomal recessive nail dysplasia in 2011. Presently, only seven mutations have been reported in FZD6 gene
An integrative study on the impact of highly differentially methylated genes on expression and cancer etiology
(PUBLIC LIBRARY SCIENCE, 2017-01-01) Ozer, Bugra; Sezerman, Ugur
DNA methylation is an important epigenetic phenomenon that plays a key role in the regulation of expression. Most of the studies on the topic of methylation's role in cancer mechanisms include analyses based on differential methylation, with the integration of expression information as supporting evidence. In the present study, we sought to identify methylationdriven patterns by also integrating protein-protein interaction information. We performed integrative analyses of DNA methylation, expression, SNP and copy number data on paired samples from six different cancer types. As a result, we found that genes that show a methylation change larger than 32.2\% may influence cancer-related genes via fewer interaction steps and with much higher percentages compared with genes showing a methylation change less than 32.2\%. Additionally, we investigated whether there were shared cancer mechanisms among different cancer types. Specifically, five cancer types shared a change in AGTR1 and IGF1 genes, which implies that there may be similar underlying disease mechanisms among these cancers. Additionally, when the focus was placed on distinctly altered genes within each cancer type, we identified various cancer-specific genes that are also supported in the literature and may play crucial roles as therapeutic targets. Overall, our novel graph-based approach for identifying methylation-driven patterns will improve our understanding of the effects of methylation on cancer progression and lead to improved knowledge of cancer etiology.
Analysis of Correlation between the Seven Important Helicobacter pylori (H. pylori) Virulence Factors and Drug Resistance in Patients with Gastritis
(HINDAWI LTD, 2020-01-01) Oktem-Okullu, Sinem; Cekic-Kipritci, Zehra; Kilic, Elif; Seymen, Nogayhan; Mansur-Ozen, Nesteren; Sezerman, Ugur; Gurol, Yesim
The aim of this study is to evaluate the association between seven importantH.pylorivirulence factors and antibiotic resistance in patients with gastritis.H.pyloristrains isolated from 33 patients with gastritis were examined. Antimicrobial susceptibilities were tested by GenoType (R) HelicoDR (Hain Life Science, Germany) test kit and RT-PCR. The virulence-factors were determined using conventional PCR. 39\% of patients were resistant for clarithromycin and 27\% of patients were resistant for fluoroquinolone. 15\% of patients were resistant to both clarithromycin and fluoroquinolone. TheH.pylori vacA m1/s2genotype was the most frequent allelic combination. Patients were possessed thevacA s1,m1(6.1\%)
Base-excess chloride
(PUBLIC LIBRARY SCIENCE, 2021-01-01) Gucyetmez, Bulent; Tuzuner, Filiz; Atalan, Hakan Korkut; Sezerman, Ugur; Gucyetmez, Kaan; Telci, Lutfi
To practically determine the effect of chloride (Cl) on the acid-base status, four approaches are currently used: accepted ranges of serum Cl values
Comparison of endometrial prostanoid profiles in three infertile subgroups: the missing part of receptivity?
(ELSEVIER SCIENCE INC, 2020-01-01) Keles, Irem Demiral; Ulgen, Ege; Erkan, Melike Belkiz; Celik, Saliha Esin; Aydin, Yasemin; Onem, Ayse Nur; Kandemir, Hulya; Arslanoglu, Tugce; Apak, Mustafa Resat; Sezerman, Ugur; Yeh, John; Buyru, Faruk; Bastu, Ercan
Objective: To study the prostanoid profile of the endometria of patients with recurrent implantation failure (RIF), unexplained infertility (UIF), and recurrent miscarriages (RM), and to compare them with the endometria of healthy fertile controls. Design: Prospective cohort study. Setting: University hospital. Patient(s): Fifteen patients with RIF, 18 patients with UIF, 16 patients with RM, and 23 fertile controls were recruited. Intervention(s): Endometrial samples were taken during the window of implantation. After tissue homogenization and extraction, analysis with ultra-performance liquid chromatography diode array detector electrospray ionisation tandemmass spectrometrywas performed. Main Outcome Measures: Concentrations of prostaglandin (PG) D1, PGE1, PGF1 alpha, 6-ketoPGF1 alpha GD2, PGE2, PGF2 alpha, 15-deoxy-Delta 12,14-PGJ2, PGD3, PGE3, PGF3 alpha, thromboxane B2, 13,14-dihydro-PGE1, 13,14-dihydro-PGF1 alpha, 13,14-dihydro-PGF2 alpha, 13,14dihydro-15-keto-PGE1, 13,14-dihydro-15-keto-PGE2, and 13,14-dihydro-15-keto-PGF2 alpha were assessed. Result(s): Comparison of the endometria of patients with UIF and the controls showed no statistically significant differences. When the endometria of patients with RIF were compared with the controls, thromboxane B2 (TXB2) was found significantly higher (843.1 pg/mg vs. 133.5 pg/mg). When the endometria of patients with RM were compared with controls, 13,14-dihydro-15-keto PGF2 alpha and TXB2 were found significantly higher (3907.30 pg/mg vs. 17.80 pg/mg and 858.7 pg/mg vs. 133.5 pg/mg respectively). Conclusion(s): We identified increased endometrial presence of TXB2 in patients with RM and RIF, and 13,14-dihydro-15-keto PGF2 alpha in patients with RM. Although common ground is observed for RM and RIF, prostanoids, on the other hand, might make their own contribution to endometrial receptivity as important as genes and proteins. Attempts to normalize the prostaglandin profile of the endometrium via enzymatic activity can open new therapeutic options. (C) 2019 by American Society for Reproductive Medicine.
Differential gene expression analysis of human cumulus cells
(KOREAN SOC REPRODUCTIVE MEDICINE, 2019-01-01) Demiray, Sirin Bakti; Goker, Ege Nazan Tavmergen; Tavmergen, Erol; Yilmaz, Ozlem; Calimlioglu, Nilufer; Soykam, Huseyin Okan; Oktem, Gulperi; Sezerman, Ugur
Objective: This study was performed to explore the possibility that each oocyte and its surrounding cumulus cells might have different genetic expression patterns that could affect human reproduction. Methods: Differential gene expression analysis was performed for 10 clusters of cumulus cells obtained from 10 cumulus-oocyte complexes from 10 patients. Same procedures related to oocyte maturation, microinjection, and microarray analyses were performed for each group of cumulus cells. Two differential gene expression analyses were performed: one for the outcome of clinical pregnancy and one for the outcome of live birth. Results: Significant genes resulting from these analyses were selected and the top 20 affected pathways in each group were analyzed. Circadian entrainment is determined to be the most affected pathway for clinical pregnancy, and proteoglycans in cancer pathway is the most affected pathway for live birth. Circadian entrainment is also amongst the 12 pathways that are found to be in top 20 affected pathways for both outcomes, and has both lowest p-value and highest number of times found count. Conclusion: Although further confirmatory studies are necessary, findings of this study suggest that these pathways, especially circadian entrainment in cumulus cells, may be essential for embryo development and pregnancy.
GUT MICROBIOTA EFFECTS IN HEMATOPOIETIC STEM CELL TRANSPLANT PATIENTS
(ISTANBUL UNIV, FAC MEDICINE, PUBL OFF, 2022-01-01) Gurer, Ekin Ece; Oguz, Fatma S. A. V. R. A. N.; Kalayoglu, Sevgi BEsIsIK.; Aktas, Zerrin; Gulbas, Zafer; Oncul, Mustafa Oral; Sezerman, Ugur
Objective: In our study, we analyzed gut microbiota in allo-HSCT patients and aimed to evaluate the relationship of gut microbio-ta with transplant complications, mainly GVHD. Materials and Methods: A total of 25 adult recipients and do-nors who underwent allo-HSCT at Istanbul Anadolu Medical Center were included in the study. Stool samples were collected twice, before chemotherapy regimen and after allo-HSCT. Sam-ples were analyzed by High Melting (HRM) Analysis and Next Generation Sequencing (NGS) methods after nucleic acid iso-lation. Sequencing was done with Illumina MiSeq. Bacteria Silva database was used for taxonomic classification and QIIME 2 pro-grams were used for analysis. Statistical analyses were carried out with the R statistical programming language. Results: Twenty-five allo-HKHN recipients were included in the study. The mean age was 46.24 +/- 14.86 years in recipients and 43.40 +/- 13.20 years in donors. Gender distribution was M/F: 15/10 in patients and M/F: 17/8 in donors. Recipient and donor sib-ling HLA match was 10/10. The rate of GVHD associated with Allo-HSCT was 16\%, and the relapse rate was 16\%. It was ob-served that the Firmicutes and Proteobacteria phyla changed significantly before and after transplantation. The number of Entereccocus species was found to be higher in patients who developed GVHD and died. The loss of diversity was found to be statistically significant in the pre-transplant and post-engraft-ment samples of the patients. Conclusion: Gut microbiota diversity may guide the monitoring of GVHD and also may be manipulated for the treatment of GVHD. It is thought that increasing the diversity of commensal bacteria can also positively affect the prognosis of the disease.
In silico analyses and global transcriptional profiling reveal novel putative targets for Pea3 transcription factor related to its function in neurons
(PUBLIC LIBRARY SCIENCE, 2017-01-01) Kandemir, Basak; Dag, Ugur; Gungor, Burcu Bakir; Durasi, Ilknur Melis; Erdogan, Burcu; Sahin, Eray; Sezerman, Ugur; Kurnaz, Isil Aksan
Pea3 transcription factor belongs to the PEA3 subfamily within the ETS domain transcription factor superfamily, and has been largely studied in relation to its role in breast cancer metastasis. Nonetheless, Pea3 plays a role not only in breast tumor, but also in other tissues with branching morphogenesis, including kidneys, blood vasculature, bronchi and the developing nervous system. Identification of Pea3 target promoters in these systems are important for a thorough understanding of how Pea3 functions. Present study particularly focuses on the identification of novel neuronal targets of Pea3 in a combinatorial approach, through curation, computational analysis and microarray studies in a neuronal model system, SH-SY5Y neuroblastoma cells. We not only show that quite a number of genes in cancer, immune system and cell cycle pathways, among many others, are either up- or down-regulated by Pea3, but also identify novel targets including ephrins and ephrin receptors, semaphorins, cell adhesion molecules, as well as metalloproteases such as kallikreins, to be among potential target promoters in neuronal systems. Our overall results indicate that rather than early stages of neurite extension and axonal guidance, Pea3 is more involved in target identification and synaptic maturation.
Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation
(NATURE PORTFOLIO, 2022-01-01) Everest, Elif; Ahangari, Mohammad; Uygunoglu, Ugur; Tutuncu, Melih; Bulbul, Alper; Saip, Sabahattin; Duman, Taskin; Sezerman, Ugur; Reich, Daniel S.; Riley, Brien P.; Siva, Aksel; Turanli, Eda Tahir
Many multiple sclerosis (MS)-associated common risk variants as well as candidate low-frequency and rare variants have been identified
Investigation of base excision repair gene variants in late-onset Alzheimer's disease
(PUBLIC LIBRARY SCIENCE, 2019-01-01) Ertuzun, Tugce; Semerci, Asli; Cakir, Mehmet Emin; Ekmekcioglu, Aysegul; Gok, Mehmet Oguz; Soltys, Daniela T.; de Souza-Pinto, Nadja C.; Sezerman, Ugur; Muftuoglu, Meltem
Base excision repair (BER) defects and concomitant oxidative DNA damage accumulation play a role in the etiology and progression of late-onset Alzheimer's disease (LOAD). However, it is not known whether genetic variant(s) of specific BER genes contribute to reduced BER activity in LOAD patients and whether they are associated with risk, development and/or progression of LOAD. Therefore, we performed targeted next generation sequencing for three BER genes, uracil glycosylase (UNG), endonuclease VIII-like DNA glycosylase 1 (NEIL1) and polymerase beta (POL beta) including promoter, exonic and intronic regions in peripheral blood samples and postmortem brain tissues (temporal cortex, TC and cerebellum, CE) from LOAD patients, high-pathology control and cognitively normal age-matched controls. In addition, the known LOAD risk factor, APOE was included in this study to test whether any BER gene variants associate with APOE variants, particularly APOE epsilon 4. We show that UNG carry five significant variants (rs1610925, rs2268406, rs80001089, rs1018782 and rs1018783) in blood samples of Turkish LOAD patients compared to age-matched controls and one of them (UNG rs80001089) is also significant in TC from Brazilian LOAD patients (p<0.05). The significant variants present only in CE and TC from LOAD are UNG rs2569987 and POL beta rs1012381950, respectively. There is also significant epistatic relationship (p = 0.0410) between UNG rs80001089 and NEIL1 rs7182283 in TC from LOAD subjects. Our results suggest that significant BER gene variants may be associated with the risk of LOAD in non-APOE epsilon 4 carriers. On the other hand, there are no significant UNG, NEIL1 and POL beta variants that could affect their protein level and function, suggesting that there may be other factors such as post-transcriptional or-translational modifications responsible for the reduced activities and protein levels of these genes in LOAD pathogenesis. Further studies with increased sample size are needed to confirm the relationship between BER variants and LOAD risk.
Molecular modelling of the FOXO4-TP53 interaction to design senolytic peptides for the elimination of senescent cancer cells
(ELSEVIER, 2021-01-01) Le, Hillary H.; Cinaroglu, Suleyman S.; Manalo, Elise C.; Ors, Aysegul; Gomes, Michelle M.; Sahbaz, Burcin Duan; Bonic, Karla; Marmolejo, Carlos A. Origel; Quentel, Arnaud; Plaut, Justin S.; Kawashima, Taryn E.; Ozdemir, E. Sila; Malhotra V, Sanjay; Ahiska, Yavuz; Sezerman, Ugur; Akcapinar, Gunseli Bayram; Saldivar, Joshua C.; Timucin, Emel; Fischer, Jared M.
Background: Senescent cells accumulate in tissues over time as part of the natural ageing process and the removal of senescent cells has shown promise for alleviating many different age-related diseases in mice. Cancer is an age-associated disease and there are numerous mechanisms driving cellular senescence in cancer that can be detrimental to recovery. Thus, it would be beneficial to develop a senolytic that acts not only on ageing cells but also senescent cancer cells to prevent cancer recurrence or progression. Methods: We used molecular modelling to develop a series of rationally designed peptides to mimic and target FOXO4 disrupting the FOXO4-TP53 interaction and releasing TP53 to induce apoptosis. We then tested these peptides as senolytic agents for the elimination of senescent cells both in cell culture and in vivo. Findings: Here we show that these peptides can act as senolytics for eliminating senescent human cancer cells both in cell culture and in orthotopic mouse models. We then further characterized one peptide, ES2, showing that it disrupts FOXO4-TP53 foci, activates TP53 mediated apoptosis and preferentially binds FOXO4 compared to TP53. Next, we show that intratumoural delivery of ES2 plus a BRAF inhibitor results in a significant increase in apoptosis and a survival advantage in mouse models of melanoma. Finally, we show that repeated systemic delivery of ES2 to older mice results in reduced senescent cell numbers in the liver with minimal toxicity. Interpretation: Taken together, our results reveal that peptides can be generated to specifically target and eliminate FOXO4+ senescent cancer cells, which has implications for eradicating residual disease and as a combination therapy for frontline treatment of cancer. Funding: This work was supported by the Cancer Early Detection Advanced Research Center at Oregon Health \& Science University. (C) 2021 The Authors. Published by Elsevier B.V.
Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis
(PUBLIC LIBRARY SCIENCE, 2015-01-01) Oktem-Okullu, Sinem; Tiftikci, Arzu; Saruc, Murat; Cicek, Bahattin; Vardareli, Eser; Tozun, Nurdan; Kocagoz, Tanil; Sezerman, Ugur; Yavuz, Ahmet Sinan; Sayi-Yazgan, Ayca
The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors
Progesterone at high doses reduces the growth of U87 and A172 glioblastoma cells: Proteomic changes regarding metabolism and immunity
(WILEY, 2020-01-01) Altinoz, Meric A.; Ucal, Yasemin; Yilmaz, Muazzez C.; Kiris, Irem; Ozisik, Ozan; Sezerman, Ugur; Ozpinar, Aysel; Elmaci, Ilhan
While pregnancy may accelerate glioblastoma multiforme (GBM) growth, parity and progesterone (P4) containing treatments (ie, hormone replacement therapy) reduce the risk of GBM development. In parallel, low and high doses of P4 exert stimulating and inhibitory actions on GBM growth, respectively. The mechanisms behind the high-dose P4-suppression of GBM growth is unknown. In the present study, we assessed the changes in growth and proteomic profiles when high-dose P4 (100 and 300 mu M) was administered in human U87 and A172 GBM cell lines. The xCELLigence system was used to examine cell growth when different concentrations of P4 (20, 50, 100, and 300 mu M) was administered. The protein profiles were determined by two-dimensional gel electrophoresis in both cell lines when 100 and 300 mu M P4 were administered. Finally, the pathways enriched by the differentially expressed proteins were assessed using bioinformatic tools. Increasing doses of P4 blocked the growth of both GBM cells. We identified 26 and 51 differentially expressed proteins (fc > 2) in A172 and U87 cell lines treated with P4, respectively. Only the pro-tumorigenic mitochondrial ornithine aminotransferase and anti-apoptotic mitochondrial 60 kDa heat shock protein were downregulated in A172 cell line and U87 cell line when treated with P4, respectively. Detoxification of reactive oxygen species, cellular response to stress, glucose metabolism, and immunity-related proteins were altered in P4-treated GBM cell lines. The paradox on the effect of low and high doses of P4 on GBM growth is gaining attention. The mechanism related to the high dose of P4 on GBM growth can be explained by the alterations in detoxification mechanisms, stress, and immune response and glucose metabolism. P4 suppresses GBM growth and as it is nontoxic in comparison to classical chemotherapeutics, it can be used as a new strategy in GBM treatment in the future.
Re-analysis of whole-exome sequencing data reveals a novel splicing variant in the SLC2A1 in a patient with GLUT1 Deficiency Syndrome 1 accompanied by hemangioma: a case report
(BMC, 2021-01-01) Bozkurt, Tugce; Alanay, Yasemin; Isik, Ugur; Sezerman, Ugur
Background GLUT1 Deficiency Syndrome 1 (GLUT1DS1) is a neurological disorder caused by either heterozygous or homozygous mutations in the Solute Carrier Family 2, Member 1 (SLC2A1) gene. SLC2A1 encodes Glucose transporter type 1 (GLUT1) protein, which is the primary glucose transporter at the blood-brain barrier. A ketogenic diet (KD) provides an alternative fuel for brain metabolism to treat impaired glucose transport. By reanalyzing exome data, we identified a de novo heterozygous SLC2A1 variant in a girl with epilepsy. After reversed phenotyping with neurometabolic tests, she was diagnosed with GLUT1DS1 and started on a KD. The patient's symptoms responded to the diet. Here, we report a patient with GLUT1DS1 with a novel SLC2A1 mutation. She also has a hemangioma which has not been reported in association with this syndrome before. Case presentation A 5-year 8-month girl with global developmental delay, spasticity, intellectual disability, dysarthric speech, abnormal eye movements, and hemangioma. The electroencephalography (EEG) result revealed that she had epilepsy. Magnetic resonance imaging (MRI) showed that non-specific white matter abnormalities. Whole Exome Sequencing (WES) was previously performed, but the case remained unsolved. The re-analysis of WES data revealed a heterozygous splicing variant in the SLC2A1 gene. Segregation analysis with parental DNA samples indicated that the variant occurred de novo. Lumbar puncture (LP) confirmed the diagnosis, and the patient started on a KD. Her seizures responded to the KD. She has been seizure-free since shortly after the initiation of the diet. She also had decreased involuntary movements, her speech became more understandable, and her vocabulary increased after the diet. Conclusions We identified a novel de novo variant in the SLC2A1 gene in a patient who previously had a negative WES result. The patient has been diagnosed with GLUT1DS1. The syndrome is a treatable condition, but the differential diagnosis is not an easy process due to showing a wide range of phenotypic spectrum and the overlapping symptoms with other neurological diseases. The diagnosis necessitates a genomic testing approach. Our findings also highlight the importance of re-analysis to undiagnosed cases after initial WES to reveal disease-causing variants.
The importance of dysregulated miRNAs on ovarian cysts and epithelial ovarian cancer
(IMR PRESS, 2021-01-01) Gumusoglu, Ece; Gunel, Tuba; Hosseini, Mohammad Kazem; Seymen, Nogayhan; Senol, Taylan; Sezerman, Ugur; Topuz, Samet; Aydinli, Kilic
Objective: Benign ovarian cysts (BOC) are the most common tumors in women of reproductive age. Usually, these cysts are harmless, but, a small number of them occasionally progress to malignancy. Among ovarian malignancies, epithelial ovarian cancer (EOC) comprises 90\% and is the most important cause of gynecologic cancerrelated deaths. We aimed to identify dysregulated miRNAs in patients with benign ovarian cysts (n = 11) compared to EOC (n = 10) and to healthy individuals (HI) (n = 15). Methods: The serum samples from EOC and BOC patients were collected before operation. We studied three different sample groups (serum of EOC (n = 8), HI (n = 8), and BOC (n = 8) patients) that contained the highest-quality of RNA. Microarray data were analyzed according to expression of miRNAs and target genes by bioinformatics tools. Results: When compared to EOC samples, 75 miRNAs were dysregulated in BOC samples. Sixty-six miRNAs from BOC were dysregulated when compared to HI samples. Bioinformatics analysis of BOC vs. EOC and BOC vs. HI showed that 46 miRNAs were congruent and their expression alterations were similar (up- or down-regulated). Further analysis showed that these 46 miRNAs are associated to one of three pathways involved in cancer pathogenesis. Conclusion: Several miRNAs might playa role in BOC formation and/or malignant transformation. These dysregulated miRNAs could potentially be a biomarker to distinguish between a completely BOC and one that is malignant or has potential for malignant transformation.
The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium inaugural meeting report
(BMC, 2016-01-01) Chernomoretz, Ariel; Stolovitzky, Gustavo; Labaj, Pawel P.; Graf, Alexandra B.; Darling, Aaron; Burke, Catherine; Noushmehr, Houtan; Moraes, Milton Ozorio; Dias-Neto, Emmanuel; Guo, Yongli; Xie, Zhi; Lee, Patrick; Shi, Leming; Ruiz-Perez, Carlos A.; Mercedes Zambrano, Maria; Siam, Rania; Ouf, Amged; Richard, Hugues; Lafontaine, Ingrid; Wieler, Lothar H.; Semmler, Torsten; Ahmed, Niyaz; Prithi-viraj, Bharath; Nedunuri, Narasimha; Mehr, Shaadi; Banihashemi, Kambiz; Lista, Florigio; Anselmo, Anna; Suzuki, Haruo; Kuroda, Makoto; Yamashita, Riu; Sato, Yukoto; Kaminuma, Eli; Alpuche Aranda, Celia M.; Martinez, Jesus; Dada, Christopher; Dybwad, Marius; Oliveira, Manuela; Schuster, Stephan; Siwo, Geoffrey H.; Jang, Soojin; Seo, Sung Chul; Hwang, Sung Ho; Ossowski, Stephan; Bezdan, Daniela; Chaker, Salama; Chatziefthimiou, Aspassia D.; Udekwu, Klas; Liungdahl, Per; Sezerman, Ugur; Meydan, Cem; Elhaik, Eran; Gonnet, Gaston; Schriml, Lynn M.; Mongodin, Emmanuel; Huttenhower, Curtis; Gilbert, Jack; Mason, Christopher E.; Eisen, Jonathan; Hirschberg, David; Hernandez, Mark; Consortium, MetaSU.B. Int
The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium is a novel, interdisciplinary initiative comprised of experts across many fields, including genomics, data analysis, engineering, public health, and architecture. The ultimate goal of the MetaSUB Consortium is to improve city utilization and planning through the detection, measurement, and design of metagenomics within urban environments. Although continual measures occur for temperature, air pressure, weather, and human activity, including longitudinal, cross-kingdom ecosystem dynamics can alter and improve the design of cities. The MetaSUB Consortium is aiding these efforts by developing and testing metagenomic methods and standards, including optimized methods for sample collection, DNA/RNA isolation, taxa characterization, and data visualization. The data produced by the consortium can aid city planners, public health officials, and architectural designers. In addition, the study will continue to lead to the discovery of new species, global maps of antimicrobial resistance (AMR) markers, and novel biosynthetic gene clusters (BGCs). Finally, we note that engineered metagenomic ecosystems can help enable more responsive, safer, and quantified cities.
Understanding the impacts of self-shuffling approach on structure and function of shuffled endoglucanase enzyme via MD simulations
(WALTER DE GRUYTER GMBH, 2020-01-01) Yenenler, Asli; Gerlevik, Umut; Sezerman, Ugur
Objective: We identify the impacts of structural differences on functionality of EG3\_S2 endoglucanase enzyme with MD studies. The results of previous experimental studies have been explained in details with computational approach. The objective of this study is to explain the functional differences between shuffled enzyme (EG3\_S2) and its native counterpart (EG3\_nat) from Trichoderma reseei, via Molecular Dynamics approach. Materials and methods: For this purpose, we performed MD simulations along 30 ns at three different reaction temperatures collected as NpT ensemble, and then monitored the backbone motion, flexibilities of residues, and intramolecular interactions of EG3\_S2 and EG3\_nat enzymes. Results: According to MD results, we conclude that EG3 S2 and EG3\_nat enzymes have unique RMSD patterns, e.g. RMSD pattern of EG3\_S2 is more dynamic than that of EG3\_nat at all temperatures. In addition to this dynamicity, EG3 S2 establishes more salt bridge interactions than EG3\_nat. Conclusion: By taking these results into an account with the preservation of catalytic Glu residues in a proper manner, we explain the structural basis of differences between shuffled and native enzyme via molecular dynamic studies.