Biyomühendislik / Bioengineering

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/208

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Akut Böbrek Hasarında Nötrofil Jelatinaz İlişkili Lipokalin ile Mortalite İlişkisi
(GALENOS YAYINCILIK, ERKAN MOR, MOLLA GURANI CAD 21-1, FINDIKZADE, ISTANBUL 34093, TURKEY, 2018) Aksebzeci, Bekir Hakan; Kayaaltı, Seda; Kayaaltı, Ömer; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü;
Objective: Almost half of intensive care patients are affected by acute kidney injury (AKI). The purpose of this study is to determine parameters that can be used for predicting of early (within 28 days) and late (within 90 days) mortality in patients who are followed-up with AKI in intensive care units. Materials and Methods: In this study, a dataset that contains 50 patients with AKI in intensive care units was used. This dataset contains blood urea nitrogen, creatinine, plasma and urinary neutrophil gelatinase-associated hpocalin (NGAL), lactate dehydrogenase, alkaline phosphatase and gammaglutamyl transpeptidase values of patients who were admitted to intensive care for various reasons and who developed AKI on the days 1, 3 and 7. In addition to these values, laboratory results such as serum electrolytes on day 1, blood gas; vital signs such as mean arterial pressure, central venous pressure; and demographic data were also recorded. Data mining techniques were applied to determine correlation between all of these data and mortality. Results: The threshold level of urinary NGAL on day 7 was determined to be 69 ng/mL, and strong correlation was found between this threshold level and early mortality. Similarly, the threshold level of plasma NGAL on day 7 was determined to be 150 ng/mL, and this was highly correlated with early mortality. Besides, strong correlation was also found between the difference in the urinary NGAL levels on day 1 and 7, and early mortality. Conclusion: In this study, plasma and urinary NGAL levels were found to be closely related to early mortality in patients who were followed-up with AKI in intensive care units. On the other hand, any parameter associated with late mortality was not found.
Analyzing the genetic diversity and biotechnological potential of Leuconostoc pseudomesenteroides by comparative genomics
(Frontiers Media S.A., 2023) Gumustop, Ismail; Ortakci, Fatih; 0000-0003-1319-0854; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Gumustop, Ismail; Ortakci, Fatih
Leuconostoc pseudomesenteroides is a lactic acid bacteria species widely exist in fermented dairy foods, cane juice, sourdough, kimchi, apple dumpster, caecum, and human adenoid. In the dairy industry, Ln. pseudomesenteroides strains are usually found in mesophilic starter cultures with lactococci. This species plays a crucial role in the production of aroma compounds such as acetoin, acetaldehyde, and diacetyl, thus beneficially affecting dairy technology. We performed genomic characterization of 38 Ln. pseudomesenteroides from diverse ecological niches to evaluate this species’ genetic diversity and biotechnological potential. A mere ~12% of genes conserved across 38 Ln. pseudomesenteroides genomes indicate that accessory genes are the driving force for genotypic distinction in this species. Seven main clades were formed with variable content surrounding mobile genetic elements, namely plasmids, transposable elements, IS elements, prophages, and CRISPR-Cas. All but three genomes carried CRISPR-Cas system. Furthermore, a type IIA CRISPR-Cas system was found in 80% of the CRISPR-Cas positive strains. AMBR10, CBA3630, and MGBC116435 were predicted to encode bacteriocins. Genes responsible for citrate metabolism were found in all but five strains belonging to cane juice, sourdough, and unknown origin. On the contrary, arabinose metabolism genes were only available in nine strains isolated from plant-related systems. We found that Ln. pseudomesenteroides genomes show evolutionary adaptation to their ecological environment due to niche-specific carbon metabolism and forming closely related phylogenetic clades based on their isolation source. This species was found to be a reservoir of type IIA CRISPR-Cas system. The outcomes of this study provide a framework for uncovering the biotechnological potential of Ln. pseudomesenteroides and its future development as starter or adjunct culture for dairy industry.
ARL13B regulates juxtaposed cilia-cilia elongation in BBSome dependent manner in Caenorhabditis elegans
(CELL PRESS, 2025) Turan, Merve Gul; Kantarci, Hanife; Cevik, Sebiha; Kaplan, Oktay I.; 0000-0002-0935-1929; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Turan, Merve Gul; Kantarci, Hanife; Cevik, Sebiha; Kaplan, Oktay I.
The interaction of cilia with various cellular compartments, such as axons, has emerged as a new form of cellular communication. Cilia often extend in proximity to cilia from neighboring cells. However, the mechanisms driving this process termed juxtaposed cilia-cilia elongation (JCE) remain unclear. We use fluorescence-based visualization to study the mechanisms of coordinated cilia elongation in sensory neurons of Caenorhabditis elegans. Conducting a selective gene-based screening strategy reveals that ARL-13/ARL13B and MKS-5/RPGRIP1L are essential for JCE. We demonstrate that ARL-13 modulates JCE independently of cilia length. Loss of NPHP-2/inversin along with HDAC-6 enhances the cilia misdirection phenotype of arl-13 mutants, while disruption of the BBSome complex, but not microtubule components, partially suppresses the JCE defects in arl-13 mutants. We further show changes in the phospholipid compositions in arl-13 mutants. We suggest that ARL-13 contributes to JCE, in part, through the modulation of the ciliary membrane.
Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature
(FRONTIERS MEDIA SA, 2023) Srivastava, Kamal; Cao, Mingzhuo; Fidan, Ozkan; Shi, Yanmei; Yang, Nan; Nowak-Wegrzyn, Anna; Miao, Mingsan; Zhan, Jixun; Sampson, Hugh A.; Li, Xiu-Min; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
BackgroundGut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function. ObjectiveWe sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatment-induced changes in gut microbiota with therapeutic outcomes. MethodsPeanut-allergic (PA) mice, orally sensitized with roasted peanut and cholera toxin, received oral BNP or control treatments. PA mice received periodic post-therapy roasted peanut exposures. Anaphylaxis was assessed by visualization of symptoms and measurement of body temperature. Histamine and serum peanut-specific IgE levels were measured by ELISA. Splenic IgE(+)B cells were assessed by flow cytometry. Fecal pellets were used for sequencing of bacterial 16S rDNA by Illumina MiSeq. Sequencing data were analyzed using built-in analysis platforms. ResultsBNP treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE, symptom scores, plasma histamine, body temperature, and number of IgE(+) B cells (p <0.001 vs Sham for all). Significant differences were observed for Firmicutes/Bacteroidetes ratio across treatment groups. Bacterial genera positively correlated with post-challenge histamine and PN-IgE included Lachnospiraceae, Ruminococcaceae, and Hydrogenanaerobacterium (all Firmicutes) while Verrucromicrobiacea. Caproiciproducens, Enterobacteriaceae, and Bacteroidales were negatively correlated. ConclusionsBNP is a promising regimen for food allergy treatment and its benefits in a murine model are associated with a distinct microbiota signature.
Biodiversity, drug discovery, and the future of global health: Introducing the biodiversity to biomedicine consortium, a call to action
(UNIV EDINBURGH, GLOBAL HEALTH SOC, CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG, SCOTLAND, 2017) Neergheen-Bhujun, Vidushi; Awan, Almas Taj; Baran, Yusuf; Bunnefeld, Nils; Chan, Kit; Edison Dela Cruz, Thomas; Egamberdieva, Dilfuza; Elsasser, Simon; Johnson, Mari-Vaughn V.; Komai, Shoji; Konevega, Andrey L.; Malone, John H.; Mason, Paul; Nguon, Rothsophal; Piper, Ross; Shrestha, Uttam Babu; Pesic, Milica; Kagansky, Alexander; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü;
[Özet Yok]
Biosynthesis of Novel Naphthoquinone Derivatives in the Commonly-used Chassis Cells Saccharomyces cerevisiae and Escherichia coli
(Pleiades journals, 2021) Wu W.; Wang S.; Zhang H.; Guo W.; Lu H.; Xu H.; Zhan R.; Fidan O.; Sun L.; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, O.
Naphthoquinones harboring 1,4-naphthoquinone pharmacophore are considered as privileged structures in medicinal chemistry. In pharmaceutical industry and fundamental research, polyketide naphthoquinones were widely produced by heterologous expression of polyketide synthases in microbial chassis cells, such as Saccharomyces cerevisiae and Escherichia coli. Nevertheless, these cell factories still remain, to a great degree, black boxes that often exceed engineers’ expectations. In this work, the biotransformation of juglone or 1,4-naphthoquinone was conducted to generate novel derivatives and it was revealed that these two naphthoquinones can indeed be modified by the chassis cells. Seventeen derivatives, including 6 novel compounds, were isolated and their structural characterizations indicated the attachment of certain metabolites of chassis cells to naphthoquinones. Some of these biosynthesized derivatives were reported as potent antimicrobial agents with reduced cytotoxic activities. Additionally, molecular docking as simple and quick in silico approach was performed to screen the biosynthesized compounds for their potential antiviral activity. It was found that compound 11 and 17 showed the most promising binding affinities against Nsp9 of SARS-CoV-2, demonstrating their potential antiviral activities. Overall, this work provides a new approach to generate novel molecules in the commonly used chassis cells, which would expand the chemical diversity for the drug development pipeline. It also reveals a novel insight into the potential of the catalytic power of the most widely used chassis cells. © 2021, Pleiades Publishing, Inc.
Characterization of genomic, physiological, and probiotic features Lactiplantibacillus plantarum DY46 strain isolated from traditional lactic acid fermented shalgam beverage
(ELSEVIER, 2022) Yetiman, Ahmet E.; Keskin, Abdullah; Darendeli, Busra Nur; Kotil, Seyfullah Enes; Ortakci, Fatih; Dogan, Mahmut; 0000-0001-5340-5106; 0000-0003-1319-0854; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Keskin, Abdullah; Ortakci, Fatih
Lactiplantibacillus plantarum is a significant probiotic where it could be found in ubiquitous niches. In this study, a new Lb. plantarum strain DY46 was isolated from a traditional lactic-acid-fermented beverage called shalgam. The whole genome of the DY46 was sequenced and obtained sequences were assembled into a 3.32 Mb draft genome using PATRIC (3.6.8.). The DY46 genome consists of a single circular chromosome of 3,332,827 bp that is predicted to carry 3219 genes, including 61 tRNA genes, 2 rRNA operons. The genome has a GC content of 44.3% includes 98 predicted pseudogenes, 25 complete or partial transposases and 3 intact prophages. The genes encoding enzymes related in the intact EMP (Embden–Meyerhof–Parnas) and PK (phosphoketolase) pathways were predicted using BlastKOALA which is an indicator of having facultative heterofermentative pathways. DY46 genome also predicted to carry genes of Pln E, Pln F and Pln K showing the antimicrobial potential of this bacterium which can be linked to in vitro antagonism tests that DY46 can inhibit S.enterica sv. Typhimurium ATCC14028, K. pneumonie ATCC13883, and P. vulgaris ATCC8427. Moreover, it is determined that all resistome found in its genome were intrinsically originated and the strain was found to be tolerant to acid and bile concentrations by mimicking human gastrointestinal conditions. In conclusion, L. plantarum DY46 is a promising bacterium that appears to have certain probiotic properties, confirmed by “in vitro” and “in silico” analyses, and is a potential dietary supplement candidate that may provide functional benefits to the host.
CiliaMiner: an integrated database for ciliopathy genes and ciliopathies
(OXFORD UNIV PRESS, 2023) Turan, Merve Gül; Orhan, Mehmet Emin; Cevik, Sebiha; Kaptan, Oktay I.; 0000-0001-5783-7168; 0000-0002-1757-1374; 0000-0002-0935-1929; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Turan, Merve Gül; Orhan, Mehmet Emin; Cevik, Sebiha; Kaptan, Oktay I.
Cilia are found in eukaryotic species ranging from single-celled organisms, such as Chlamydomonas reinhardtii, to humans, but not in plants. The ability to respond to repellents and/or attractants, regulate cell proliferation and differentiation and provide cellular mobility are just a few examples of how crucial cilia are to cells and organisms. Over 30 distinct rare disorders generally known as ciliopathy are caused by abnormalities or functional impairments in cilia and cilia-related compartments. Because of the complexity of ciliopathies and the rising number of ciliopathies and ciliopathy genes, a ciliopathy-oriented and up-to-date database is required. Here, we present CiliaMiner, a manually curated ciliopathy database that includes ciliopathy lists collected from articles and databases. Analysis reveals that there are 55 distinct disorders likely related to ciliopathy, with over 4000 clinical manifestations. Based on comparative symptom analysis and subcellular localization data, diseases are classifed as primary, secondary or atypical ciliopathies. CiliaMiner provides easy access to all of these diseases and disease genes, as well as clinical features and gene-specifc clinical features, as well as subcellular localization of each protein. Additionally, the orthologs of disease genes are also provided for mice, zebrafsh, Xenopus, Drosophila, Caenorhabditis elegans and Chlamydomonas reinhardtii. CiliaMiner (https://kaplanlab.shinyapps.io/ciliaminer) aims to serve the cilia community with its comprehensive content and highly enriched interactive heatmaps, and will be continually updated.
Circular RNA-MicroRNA-MRNA interaction predictions in SARS-CoV-2 infection
(WALTER DE GRUYTER GMBHGENTHINER STRASSE 13, D-10785 BERLIN, GERMANY, 2021) Demirci, Yilmaz Mehmet; Demirci, Muserref Duygu Sacar; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Demirci, Yilmaz Mehmet; Demirci, Muserref Duygu Sacar
Different types of noncoding RNAs like microRNAs (miRNAs) and circular RNAs (circRNAs) have been shown to take part in various cellular processes including post-transcriptional gene regulation during infection. MiRNAs are expressed by more than 200 organisms ranging from viruses to higher eukaryotes. Since miRNAs seem to be involved in host-pathogen interactions, many studies attempted to identify whether human miRNAs could target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNAs as an antiviral defence mechanism. In this work, a machine learning based miRNA analysis work flow was developed to predict differential expression patterns of human miRNAs during SARS-CoV-2 infection. In order to obtain the graphical representation of miRNA hairpins, 36 features were defined based on the secondary structures. Moreover, potential targeting interactions between human circRNAs and miRNAs as well as human miRNAs and viral mRNAs were investigated.
Comparative Genomics of Lentilactobacillus parabuchneri isolated from dairy, KEM complex, Makgeolli, and Saliva Microbiomes
(BMC, 2022) Gumustop, Ismail; Ortakci, Fatih; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Ortakçı, Fatih; Gümüştop, İsmail
Background: Lentilactobacillus parabuchneri is of particular concern in fermented food bioprocessing due to causing unwanted gas formation, cracks, and off-flavor in fermented dairy foods. This species is also a known culprit of histamine poisonings because of decarboxylating histidine to histamine in ripening cheese. Twenty-eight genomes in NCBI GenBank were evaluated via comparative analysis to determine genomic diversity within this species and identify potential avenues for reducing health associated risks and economic losses in the food industry caused by these organisms. Result: Core genome-based phylogenetic analysis revealed four distinct major clades. Eight dairy isolates, two strains from an unknown source, and a saliva isolate formed the first clade. Three out of five strains clustered on clade 2 belonged to dairy, and the remaining two strains were isolated from the makgeolli and Korean effective microorganisms (KEM) complex. The third and fourth clade members were isolated from Tete de Moine and dairy-associated niches, respectively. Whole genome analysis on twenty-eight genomes showed similar to 40% of all CDS were conserved across entire strains proposing a considerable diversity among L. parabuchneri strains analyzed. After assigning CDS to their corresponding function, similar to 79% of all strains were predicted to carry putative intact prophages, and similar to 43% of the strains harbored at least one plasmid; however, all the strains were predicted to encode genomic island, insertion sequence, and CRISPR-Cas system. A type I-E CRISPR-Cas subgroup was identified in all the strains, with the exception of DSM15352, which carried a type II-A CRISPR-Cas system. Twenty strains were predicted to encode histidine decarboxylase gene cluster that belongs to not only dairy but also saliva, KEM complex, and unknown source. No bacteriocin-encoding gene(s) or antibiotic resistome was found in any of the L. parabuchneri strains screened. Conclusion: The findings of the present work provide in-depth knowledge of the genomics of L. parabuchneri by comparing twenty-eight genomes available to date. For example, the hdc gene cluster was generally reported in cheese isolates; however, our findings in the current work indicated that it could also be encoded in those strains isolated from saliva, KEM complex, and unknown source. We think prophages are critical mobile elements of L. parabuchneri genomes that could pave the way for developing novel tools to reduce the occurrence of this unwanted species in the food industry.
Comparative genomics of Leuconostoc lactis strains isolated from human gastrointestinal system and fermented foods microbiomes
(BMCCAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, 2022) Gümüştop, İsmail; Ortakçı, Fatih; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Gümüştop, İsmail; Ortakçı, Fatih
Background: Leuconostoc lactis forms a crucial member of the genus Leuconostoc and has been widely used in the fermentation industry to convert raw material into acidified and flavored products in dairy and plant-based food systems. Since the ecological niches that strains of Ln. lactis being isolated from were truly diverse such as the human gut, dairy, and plant environments, comparative genome analysis studies are needed to better understand the strain differences from a metabolic adaptation point of view across diverse sources of origin. We compared eight Ln. lactis strains of 1.2.28, aa_0143, BIOML-A1, CBA3625, LN19, LN24, WIKIM21, and WiKim40 using bioinformatics to elucidate genomic level characteristics of each strain for better utilization of this species in a broad range of applications in food industry. Results: Phylogenomic analysis of twenty-nine Ln. lactis strains resulted in nine clades. Whole-genome sequence analysis was performed on eight Ln. lactis strains representing human gastrointestinal tract and fermented foods microbiomes. The findings of the present study are based on comparative genome analysis against the reference Ln. lactis CBA3625 genome. Overall, a similar to 41% of all CDS were conserved between all strains. When the coding sequences were assigned to a function, mobile genetic elements, mainly insertion sequences were carried by all eight strains. All strains except LN24 and WiKim40 harbor at least one intact putative prophage region, and two of the strains contained CRISPR-Cas system. All strains encoded Lactococcin 972 bacteriocin biosynthesis gene clusters except for CBA3625. Conclusions: The findings in the present study put forth new perspectives on genomics of Ln. lactis via complete genome sequence based comparative analysis and further determination of genomic characteristics. The outcomes of this work could potentially pave the way for developing elements for future strain engineering applications.
Comparative genomics of Loigolactobacillus coryniformis with an emphasis on L. coryniformis strain FOL-19 isolated from cheese
(ELSEVIER, 2023) Gumustop, Ismail; Ortakci, Fatih; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Gumustop, Ismail
Loigolactobacillus coryniformis is a member of lactic acid bacteria isolated from various ecological niches. We isolated a novel L. coryniformis strain FOL-19 from artisanal Tulum cheese and performed the whole-genome sequencing for FOL-19. Then, genomic characterization of FOL-19 against ten available whole genome sequences of the same species isolated from kimchi, silage, fermented meat, air of cowshed, dairy, and pheasant chyme was performed to uncover the genetic diversity and biotechnological potential of overall species. The average genome size of 2.93 +/- 0.1 Mb, GC content of 42.96% +/- 0.002, number of CDS of 2905 +/- 165, number of tRNA of 56 +/- 10, and number of CRISPR elements of 6.55 +/- 1.83 was found. Both Type I and II Cas clusters were observed in L. coryniformis. No bacteriocin biosynthesis gene clusters were found. All strains harbored at least one plasmid except KCTC 3167. All strains were predicted to carry multiple IS elements. The most common origin of the IS elements was belong to Lactiplantibacillus plantarum. Comparative genomic analysis of L. coryniformis revealed hypervariability at the strain level and the presence of CRISPR/Cas suggests that L. coryniformis holds a promising potential for being a reservoir for new CRISPR-based tools. All L. coryniformis strains except PH-1 were predicted to harbor pdu and cbi-cob-hem gene clusters encoding industrially relevant traits of reuterin and cobalamin biosynthesis, respectively. These findings put a step forward for the genomic characterization of L. coryniformis strains for biotechnological applications via genome-guided strain selection to identify industrially relevant traits.
A comprehensive study on automatic non-informative frame detection in colonoscopy videos
(WILEY, 2024) Kaçmaz, Rukiye Nur; Doğan, Refika Sultan; Yılmaz, Bülent; 0000-0001-8416-1765; 0000-0003-2954-1217; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Doğan, Refika Sultan; Yılmaz, Bülent
Despite today's developing healthcare technology, conventional colonoscopy is still a gold-standard method to detect colon abnormalities. Due to the folded structure of the intestine and visual disturbances caused by artifacts, it can be hard for specialists to detect abnormalities during the procedure. Frames that include artifacts such as specular reflection, improper contrast levels from insufficient or excessive illumination gastric juice, bubbles, or residuals should be detected to increase an accurate diagnosis rate. In this work, both conventional machine learning and transfer learning methods have been used to detect non-informative frames in colonoscopy videos. The conventional machine learning part consists of 5 different types of texture features, which are gray level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), neighborhood gray-tone difference matrix (NGTDM), focus measure operators (FMOs), and first-order statistics. In addition to these methods, we utilized 8 different transfer learning models: AlexNet, SqueezeNet, GoogleNet, ShuffleNet, ResNet50, ResNet18, NasNetMobile, and MobileNet. The results showed that FMOs and decision tree combination gave the best accuracy and f-measure values with almost 89% and 0.79%, respectively, for the conventional machine learning part. When the transfer learning part is taken into account, AlexNet (99.85%) and SqueezeNet (98.80%) have the highest performance metric results. This study shows the potential of both transfer learning and conventional machine learning algorithms to provide fast and accurate non-informative frame detection to be used during a colonoscopy, which may be considered the initial step in identifying and classifying colon-related diseases automatically to help guide physicians.
A decision support system for the prediction of mortality in patients with acute kidney injury admitted in intensive care unit
(UNIV SOUTH BOHEMIA, FAC HEALTH & SOCIAL STUD, JIROVCOVA, CESKA BUDEJOVICE, 370 04, CZECH REPUBLIC, 2020) Kayaalti, Selda; Kayaalti, Omer; Aksebzeci, Bekir Hakan; 0000-0001-6711-2363; 0000-0002-1630-1241; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Intensive care unit (ICU) is a very special unit of a hospital, where healthcare professionals provide treatment and, later, close followup to the patients. It is crucial to estimate mortality in ICU patients from many viewpoints. The purpose of this study is to classify the status of patients with acute kidney injury (AKI) in ICU as early mortality, late mortality, and survival by the application of Classification and Regression Trees (CART) algorithm to the patients' attributes such as blood urea nitrogen, creatinine, serum and urine neutrophil gelatinase-associated lipocalin (NGAL), alkaline phosphatase, lactate dehydrogenase (LDH), gamma-glutamyl transferase, laboratory electrolytes, blood gas, mean arterial pressure, central venous pressure and demographic details of patients. This study was conducted 50 patients with AKI who were followed up in the ICU. The study also aims to determine the significance of relationship between the attributes used in the prediction of mortality in CART and patients' status by employing the Kruskal-Wallis H test. The classification accuracy, sensitivity, and specificity of CART for the tested attributes for the prediction of early mortality, late mortality, and survival of patients were 90.00%, 83.33%, and 91.67%, respectively. The values of both urine NGAL and LDH on day 7 showed a considerable difference according to the patients' status after being examined by the Kruskal-Wallis H test.
Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS‑CoV‑2 through computational drug repurposing
(SPRINGER, VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS, 2022) Fidan, Özkan; Mujwar, Somdutt; Kciuk, Mateusz; 0000-0001-5312-4742; 0000-0002-8616-3825; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Özkan
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been signifcantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classifed as “variant of concern” due to their increased transmissibility and better viral ftness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous variants of concern, the Omicron variant has 15 mutations on the receptor-binding domain of spike protein and the changes in the key amino acid residues of S protein can enhance the binding ability of the virus to hACE2, resulting in a signifcant increase in the infectivity of the Omicron variant. Therefore, there is still an urgent need for treatment and prevention of variants of concern, particularly for the Omicron variant. In this study, an in silico drug repurposing was conducted through the molecular docking of 2890 FDA-approved drugs against the mutant S protein of SARS-CoV-2 for Omicron variant. We discovered promising drug candidates for the inhibition of alarming Omicron variant such as quinestrol, adapalene, tamibarotene, and dihydrotachysterol. The stability of ligands complexed with the mutant S protein was confrmed using MD simulations. The lead compounds were further evaluated for their potential use and side efects based on the current literature. Particularly, adapalene, dihydrotachysterol, levocabastine and bexarotene came into prominence due to their non-interference with the normal physiological processes. Therefore, this study suggests that these approved drugs can be considered as drug candidates for further in vitro and in vivo studies to develop new treatment options for the Omicron variant of SARS-CoV-2
Draft genome of carotenoid-producing endophytic Pseudomonas sp. 102515 from Taxus chinensis
(American Society for Microbiology, 2024) Fidan, Ozkan; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
Here, we report the draft genome sequence of endophytic Pseudomonas sp. 102515 isolated from Taxus chinensis collected from Logan, UT, USA. The genome is composed of 36 contigs and around 4.9 Mbp in size. The GC content is 66% with an N50 length of 918.9 kbp and L50 count of 2.
Editorial: Microbial production of medicinally important agents
(FRONTIERS MEDIA SA, 2023) Zeng, Jia; Zhan, Jixun; Qiao, Xue; Fidan, Ozkan; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
Harnessing microbial systems as bio-factories for the production of medically significant agents presents a thriving avenue in pharmaceutical research. From manufacturing natural products, including potent secondary metabolites, to the sophisticated engineering of recombinant proteins, microbial production’s contributions are manifold (Katz and Baltz, 2016). A salient trend is the rapid evolution of synthetic and molecular biology tools, which substantially enhance our capacity to manipulate microbial metabolism (Keasling, 2012; Ko et al., 2020). Furthermore, refinements in bioprocessing strategies have significantly improved the overall yield of microbial products, emphasizing the cost-effectiveness and efficiency of microbial production (Garcia-Ochoa and Gomez, 2009; Sharma et al., 2020). These advancements, in tandem with predictive technologies such as machine learning for optimal microbial strain selection and fermentation condition prediction, showcase this field’s innovative trajectory.
Elucidating the complex membrane binding of a protein with multiple anchoring domains using extHMMM
(Public Library of Science, 2024) Madsen, Jesper J.; Ohkubo, Y. Zenmei; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Ohkubo, Y. Zenmei
Membrane binding is a crucial mechanism for many proteins, but understanding the specific interactions between proteins and membranes remains a challenging endeavor. Coagulation factor Va (FVa) is a large protein whose membrane interactions are complicated due to the presence of multiple anchoring domains that individually can bind to lipid membranes. Using molecular dynamics simulations, we investigate the membrane binding of FVa and identify the key mechanisms that govern its interaction with membranes. Our results reveal that FVa can either adopt an upright or a tilted molecular orientation upon membrane binding. We further find that the domain organization of FVa deviates (sometimes significantly) from its crystallographic reference structure, and that the molecular orientation of the protein matches with domain reorganization to align the C2 domain toward its favored membranenormal orientation. We identify specific amino acid residues that exhibit contact preference with phosphatidylserine lipids over phosphatidylcholine lipids, and we observe that mostly electrostatic effects contribute to this preference. The observed lipid-binding process and characteristics, specific to FVa or common among other membrane proteins, in concert with domain reorganization and molecular tilt, elucidate the complex membrane binding dynamics of FVa and provide important insights into the molecular mechanisms of protein-membrane interactions. An updated version of the HMMM model, termed extHMMM, is successfully employed for efficiently observing membrane bindings of systems containing the whole FVa molecule.
Emerging DNA Methylome Targets in FLT3-ITD-Positive Acute Myeloid Leukemia: Combination Therapy with Clinically Approved FLT3 Inhibitors
(SPRINGER LINK, 2024) Tecik, Melisa; Adan, Aysun; 0000-0002-3747-8580; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Tecik, Melisa; Adan, Aysun
The internal tandem duplication (ITD) mutation of the FMS-like receptor tyrosine kinase 3 (FLT3-ITD) is the most common mutation observed in approximately 30% of acute myeloid leukemia (AML) patients. It represents poor prognosis due to continuous activation of downstream growth-promoting signaling pathways such as STAT5 and PI3K/AKT. Hence, FLT3 is considered an attractive druggable target; selective small FLT3 inhibitors (FLT3Is), such as midostaurin and quizartinib, have been clinically approved. However, patients possess generally poor remission rates and acquired resistance when FLT3I used alone. Various factors in patients could cause these adverse effects including altered epigenetic regulation, causing mainly abnormal gene expression patterns. Epigenetic modifications are required for hematopoietic stem cell (HSC) self-renewal and differentiation; however, critical driver mutations have been identified in genes controlling DNA methylation (such as DNMT3A, TET2, IDH1/2). These regulators cause leukemia pathogenesis and affect disease diagnosis and prognosis when they co-occur with FLT3-ITD mutation. Therefore, understanding the role of different epigenetic alterations in FLT3-ITD AML pathogenesis and how they modulate FLT3I’s activity is important to rationalize combinational treatment approaches including FLT3Is and modulators of methylation regulators or pathways. Data from ongoing pre-clinical and clinical studies will further precisely define the potential use of epigenetic therapy together with FLT3Is especially after characterized patients’ mutational status in terms of FLT3 and DNA methlome regulators.
Engineered Production of Bioactive Natural Products from Medicinal Plants
(WOLTERS KLUWER MEDKNOW, 2022) Fidan, Ozkan; Ren, Jie; Zhan, Jixun; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Özkan, Fidan
Plant natural products have been particularly important due to their use in food, cosmetic, and pharmaceutical industries. In particular, Traditional Chinese Medicine provides a precious potential for the discovery of bioactive natural products and development of novel modern medicines. However, the existing production methods for plant natural products such as chemical synthesis and plant extraction does not meet the current demand. Due to their environmental and economic concerns, engineered production of valuable natural products in microbial hosts has become an attractive alternative platform. This review covers the recent advances in the engineered production of plant natural products in microorganisms. A special focus was placed on the biotechnological production of plant‑derived terpenoids, flavonoids, and alkaloids. Some successful examples of engineered production of plant natural products (or their precursors) such as artemisinin, paclitaxel, naringenin, quercetin, berberine, and noscapine are summarized. This clearly indicates that the engineered production method is a promising approach with various advantages over current methods.

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