PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
Browse
66 results
Search Results
Article Predicting Respiratory Infection and Symptoms Development Using Gene Set Enrichment Scores and Machine Learning(Elsevier Sci Ltd, 2026) Aydin, Zafer; Isik, Yunus EmreRecent advancements in precision medicine enable personalized predictions grounded in individual-level genetic data. However, relying solely on a single type of data can decrease prediction accuracy and limit the biological interpretability of the resulting models. Incorporating predefined genetic knowledge, such as derived gene sets, can improve performance and provide deeper biological insights for complex diseases, including respiratory infections. This study aimed to evaluate the usability of enrichment scores (ES), calculated using gene sets from the Molecular Signatures Database (MSigDB), as a feature representation for machine learning models to predict respiratory viral infections and symptom development. In addition, the proposed feature representation approach was extensively compared with the de facto gene-level expression representation. A total of 36,834 predefined gene sets were compiled from the MSigDB, and their ES values were calculated. Experiments used the GSE73072 dataset from Gene Expression Omnibus, containing gene expression profiles before and after virus exposure. Various machine learning and feature selection algorithms were applied to ES-based and probe-level feature sets. The results showed that both feature representation approaches achieved an area under the precision-recall curve (AUPRC) value greater than 0.90 for all tasks. Compared with the Respiratory Viral DREAM Challenge leaderboard phase, our models showed a 14.8% improvement in pre-exposure predictions (T0) and a 17.4% improvement in symptom classification. Using enrichment scores as a feature representation generally resulted in better performance than probe-level representation when predicting respiratory infections and symptom development. Identifying key gene sets through feature selection and comparing them with essential genes for respiratory viruses enabled a more comprehensive analysis, providing deeper insights into the pathways that contribute to these predictions.Article Citation - WoS: 5Citation - Scopus: 5Targeting Cholinergic Dysfunction and Neuroinflammation through Rationally Designed Thieno[3,2-d]Pyrimidine Hybrids(Academic Press Inc Elsevier Science, 2026-07) Acar, Ozden Ozgun; Acar, Busra; Senol, Halil; Tokali, Feyzi Sinan; Sen, Alaattin; Demir, Yeliz; Cakir, FurkanNeurodegenerative diseases involve the convergence of cholinergic dysfunction, neuronal loss, and sustained neuroinflammatory responses, necessitating the development of multifunctional therapeutic agents. In this study, a series of novel thieno[3,2-d]pyrimidine-phenolic Mannich base hybrids were rationally designed, synthesized, and evaluated as dual cholinesterase inhibitors with neuroprotective and anti-neuroinflammatory potential. The synthesized compounds exhibited potent inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with inhibition constants in the low nanomolar range. Among them, compounds 5 and 9 emerged as the most active derivatives, displaying Ki values of 8.79 and 14.11 nM for AChE and 7.04 and 11.75 nM for BChE, surpassing the reference inhibitors tacrine and donepezil. Molecular docking and molecular dynamics simulations supported the experimental findings, and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free energy calculations further confirmed their superior binding affinities compared with donepezil. Cytotoxicity profiling in SH-SY5Y neuronal cells and RAW 264.7 and THP-1 immune cells identified a narrow sub-cytotoxic concentration window (EC05-EC10 = 1.2-2.1 mu M), ensuring biological effects independent of nonspecific cell damage. Within this range, both compounds exerted pronounced antineuroinflammatory activity. Notably, compound 9 significantly downregulated pro-inflammatory mediators, reducing IL-1 beta, IL-6, and NF-kappa B1 gene expression by up to 2.78-, 3.37-, and 4.84-fold, respectively. Consistently, it suppressed nitric oxide production in LPS-stimulated macrophages to levels comparable with ascorbic acid and markedly decreased Iba1 expression in activated THP-1 cells. This integrated enzymatic, computational, and cellular investigation identifies compounds 5 and 9 as promising multifunctional lead combining dual cholinesterase inhibition with robust anti-neuroinflammatory activity. The results provide a strong foundation for future in vivo studies and further optimization toward disease-modifying agents for neurodegenerative disorders.Article Integrative Bioinformatics Prediction of West Nile Virus-Derived microRNAs Reveals Potential Host Regulatory Interactions(Elsevier Sci Ltd, 2026-08) Demirci, Muserref Duygu Sacar; Orhan, Mehmet Emin; Erginkoc, Altay Nida; Saçar Demirci, Müşerref DuyguWest Nile virus (WNV) is a mosquito-borne flavivirus linked to severe neuroinvasive disease. Although host and vector microRNAs (miRNAs) have been implicated in viral infection, the presence and functional relevance of WNV-encoded miRNAs remain largely unexplored. Here, we developed an integrative bioinformatics pipeline that combines multiple miRNA prediction algorithms with secondary structure screening and host transcriptomic data to identify high-confidence candidate WNV-derived mature miRNAs. Overlap-based confidence scoring and differential expression support from RNA-seq datasets prioritized a small subset of putative miRNA-mRNA interactions with potential roles in infection-associated gene regulation. A competitive endogenous RNA network constructed from predicted mRNA, lncRNA, and circRNA targets highlighted pathways involving innate immunity, GPCR and Wnt signaling, RNA degradation, and viral replication. Together, these findings provide a reproducible computational workflow and nominate testable regulatory interactions for future experimental validation.Article Bi-Allelic Variants in OLA1 Cause a Neurodevelopmental Disorder with Joint Hypermobility(Cell Press, 2026-04) Cevik, Sebiha; Alzahrani, Fatema; Sezer, Abdullah; AlAbdi, Lama; Demir, Zanyar; Abdullah, Nor Linda; Alkuraya, Fowzan S.Cytoskeletal organization, cell adhesion, and cell motility are key to neuronal development and functional synapses. Obg-like ATPase 1 (OLA1) regulates cell-matrix adhesion by modulating focal adhesion kinase (FAK) levels, therefore regulating cytoskeletal dynamics and cell motility. To date, however, no Mendelian phenotypes in humans have been linked to OLA1. We identified fourteen individuals from nine families in whom hypermobility-neurodevelopmental disorder with distinct facies is linked to bi-allelic deleterious variants in OLA1. The hypermobility phenotype evoked a diagnosis of Ehlers-Danlos syndrome (EDS) in some affected individuals. The loss-of-function nature of these variants is confirmed in proband-derived fibroblasts, recapitulating the impaired migration and proliferation phenotype previously described in OLA1-deficient cells. To explore the pathogenesis of abnormal neurodevelopment in our probands, we investigated neurons derived from proband fibroblasts and identified impaired adhesion and cytoskeletal control. Modeling ola-1 deficiency in C. elegans revealed reduced neurite numbers compared to the wild type. Additionally, transcriptomic analysis of the ola-1-deficient worms suggested that dysregulation of key signaling pathways results in suppression of microtubule dynamics and axon regrowth, ultimately crippling the regenerative competence of mutant animals compared to wild-type controls. Our results support an autosomal-recessive OLA1-related hypermobility-neurodevelopmental disorder and suggest that dysregulation of key signaling pathways results in the suppression of microtubule dynamics as a potential underlying mechanism.Article GraphUnet-SS: A Novel Deep Learning Model for Protein Secondary Structure Prediction Based on U-Net Architecture(Elsevier Ltd, 2026-04) Aydin, Zafer; Görmez, Yasin; Sabzekar, MostafaArticle Citation - WoS: 3Citation - Scopus: 3Two-Local Modifications of Sachdev-Ye Model With Quantum Chaos(American Physical Society, 2026-01-27) Hanada, M.; Van Leuven, S.; Oktay, O.; Tezuka, M.The Sachdev-Ye-Kitaev (SYK) model may provide us with a good starting point for the experimental study of quantum chaos and holography in the laboratory. Still, the four-local interaction of fermions makes quantum simulation challenging, and it would be good to search for simpler models that keep the essence. In this paper, we argue that the four-local interaction may not be important by introducing a few models that have two-local interactions. The first model is a generalization of the spin-SYK model, which is obtained by replacing the spin variables with SU(d) generators. Simulations of this class of models might be straightforward on qudit-based quantum devices. We study the case of d=3,4,5,6 numerically and observe quantum chaos already for two-local interactions in a wide energy range. We also introduce modifications of spin-SYK and SYK models that have similar structures as the SU(d) model (e.g., H=∑p,qJpqχpχp+1χqχq+1 instead of the original SYK Hamiltonian H=∑p,q,r,sJpqrsχpχqχrχs), which shows strongly chaotic features although the interaction is essentially two-local. These models may be a good starting point for the quantum simulation of the original SYK model. ©2026 American Physical Society.Article Citation - WoS: 1Citation - Scopus: 1Development and Characterization of Starch-Fatty Acid Complexes Produced with Buckwheat Starch and Capric/Stearic Acid Using Different Reaction Conditions(Elsevier, 2025-12) Oskaybas-Emlek, Betul; Ozbey, Ayse; Aydemir, Levent Yurdaer; Kahraman, KevserThe aim of present study was to investigate the impact of reaction parameters on the complex formation between buckwheat starch and capric acid (B-Capric) or stearic acid (B-Stearic). The most effective parameters on complex formation indicator (Complex index (CI) value) were found as reaction temperature (60-90 degrees C) and pH (5-8). Additionally, the effect of these parameters on physicochemical, pasting, and in-vitro digestibility properties of complex samples were evaluated. XRD and FTIR was also used in characterize the complex samples. In general, increasing pH increased the CI values of B-Stearic samples while decreasing those of B-Capric samples. Syneresis of buckwheat starch increased after complexation while paste clarity and swelling power diminished. The pasting properties of native starch significantly changed after complex formation. The FTIR results showed that starch structure changed with complex formation. XRD revealed that buckwheat starch, having an A-type pattern, converted to V-type pattern after complexation. Complex formation of buckwheat starch with capric and stearic acid significantly increased the RS content of buckwheat starch (19.01 %) by up to 36.25 % and 30.60 %, respectively. These results highlight the possibility of using buckwheat starch-capric acid/stearic acid complexes in food formulation to enhance the RS content.Article Citation - WoS: 4Citation - Scopus: 4Pangenome Analysis and Genome-Guided Probiotic Evaluation of Cyclic Dipeptides Producing Levilactobacillus Brevis DY55bre Strain From a Lactic Acid Fermented Shalgam to Assess Its Metabolic, Probiotic Potentials, and Cytotoxic Effects on Colorectal Cancer Cells(Springer, 2025-10-01) Yetiman, Ahmet E.; Horzum, Mehmet; Kanbur, Ertan; Cadir, Mehmet; Bahar, Dilek; Gurbuz, Serife; Akbulut, MikailThis study investigates the genetic, metabolic, and probiotic characteristics of Levilactobacillus brevis DY55bre, a strain isolated from the traditional Turkish fermented beverage, shalgam. Whole-genome sequencing revealed a circular genome of 2.485 Mb with a GC content of 45.72%, predicted 2791 genes, and multiple CRISPR-Cas systems. Pangenome analysis demonstrated an open structure, with 18.9% core genes and 103 strain-specific genes, highlighting its genetic diversity. The DY55bre exhibits heterofermentative carbohydrate metabolism due to the presence of the araBAD operon and the lack of 1-phosphofructokinase (pfK) and fructose-1,6-bisphosphate aldolase enzymes. Probiotic evaluation revealed firm survival under simulated gastrointestinal conditions, including resistance to acidic pH (as low as 3.0) and bile salts (up to 1%), along with significant adhesion to intestinal epithelial cell lines (HT29;59.3%, Caco-2;87%, and DLD-1;60.8%). The strain exhibited high auto-aggregation (84.55%) and cell surface hydrophobicity (56.69%), essential for gut colonization. Safety assessments confirmed its non-hemolytic nature and absence of horizontally acquired antibiotic resistance genes. Notably, GC-MS analysis identified bioactive cyclic dipeptides, Cyclo(D-Phe-L-Pro) and Cyclo(L-Leu-L-Pro), which demonstrated cytotoxic effects against colorectal cancer cell lines, with IC50 values of 7.71 mg/mL for HT29 and 3.19 mg/mL for DLD-1. The cell-free supernatant exhibited antimicrobial activity against pathogens, likely due to the synergistic effects of cyclic dipeptides, organic acids, and other metabolites. Antioxidant assays revealed significant ABTS+ (76.63%) and DPPH (34.25%) radical scavenging activities, while cholesterol assimilation tests showed a 27.29% reduction. These findings position the DY55bre as a promising candidate for functional foods, nutraceuticals, and therapeutic applications, warranting further in vivo validation.Article Citation - WoS: 16Citation - Scopus: 17Unravelling the Moderating Roles of Environmental Regulations on the Impact of Foreign Direct Investment on Environmental Sustainability(Academic Press Ltd- Elsevier Science Ltd, 2025-02) Ehigiamusoe, Kizito Uyi; Chen, Danqing; Dogan, Eyup; Binsaeed, Rima H.In the era of economic globalization, China attracts significant foreign direct investment (FDI) to accelerate economic prosperity. FDI inflows could have ramifications on environmental degradation (ED) despite the enactment of different environmental regulations (ERs) such as market-incentive, command-and-control as well as informal regulations. Though some studies have shown that FDI and ED have significant relationship, the moderating roles of different ERs on the environmental impact of FDI has not been empirically unraveled. This study fills this research gap by analyzing the direct impact of FDI on ED (i.e., carbon dioxide emissions, ecological footprint) using the provincial panel data. Second, it unravels the moderating roles of different ERs on the environmental impact of FDI in the provinces and regions. The results indicate that FDI directly mitigates ED, verifying the pollution halo hypothesis while ERs directly alleviate ED in China. However, the interaction between FDI and ERs do not alleviate ED in China albeit regional heterogeneity exist. The economic implication is that FDI is not a channel through which ERs enhance environmental sustainability in China. This study recommends some policy options arising from the findings.Article Citation - WoS: 23Citation - Scopus: 28Ultra-Rapid Catalytic Degradation of 4-Nitrophenol With Ionic Liquid Recoverable and Reusable Ibuprofen Derived Silver Nanoparticles(Elsevier Sci Ltd, 2018-06) Hassan, Syeda Sara; Carlson, Krista; Mohanty, Swomitra Kumar; Sirajuddin; Canlier, AliThis study reports a one-pot and eco-friendly method for the synthesis of spherical ibuprofen derived silver nanoparticles (IBU-AgNPs) in aqueous media using ibuprofen analgesics drug as capping as well as reducing agent. Formation of AgNPs occurred within a few min (less than 5 min) at room temperature without resorting to any harsh conditions and hazardous organic solvents. Synthesized AgNPs were characterized with common analytical techniques. Transmission electron microscope (TEM) images confirmed the formation of spherical particles having a size distribution in the range of 12.5 +/- 1.5 nm. Employment of IBU analgesic aided the control of better size distribution and prevented agglomeration of particles. Such AgNPs solution was highly stable for more than two months when stored at ambient temperature. The IBU-AgNPs solution showed excellent ultra-rapid catalytic activity for the complete degradation of toxic 4-nitrophenol (4-NPh) into non-toxic 4-aminophenol (4-APh) within 40 s. AgNPs were recovered with the help of water insoluble-room temperature ionic liquid and reused with enhanced catalytic potential. This method provides a novel, rapid and economical alternative for the treatment of toxic organic pollutants to maintain water quality and environmental safety against water pollution. It is extendable for the control of other reducible contaminants in water as well. Furthermore, this catalytic activity for an effective degradation of organic toxins is expected to play a crucial role for achieving the Sustainable Development Goal 6 set by United Nations. (C) 2017 Elsevier Ltd. All rights reserved.