PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Linking RNA Methylation to Structure: A Biophysical Perspective(Wiley, 2026) Akgul, Bunyamin; Guler, Gunnur; Saglam, Buket; Akkus, Onur; Akcaoz-Alasar, AzimeRecent epitranscriptomic studies show that ribonucleic acids (RNAs) are coated with an array of chemical modifications that dictate their cellular fate. Genetic, biochemical, and genomic approaches have been employed to elucidate the molecular details of RNA methylation, one of the most prevalent types of RNA modifications with significant implications for health and disease. Various biochemical approaches have been developed to identify RNA methylations both at the global and nucleotide resolution levels. However, simpler detection methods are needed to assess the global methylation status of synthetic or cellular RNAs. Although significant progress has been made in elucidating the factors involved in writing, erasing, or reading methylated epitopes or structures, the impact of these methyl moieties on the secondary structure of RNAs or macromolecular interactions remains to be fully understood. Typically, biophysical approaches, such as Fourier transformed-infrared (FT-IR) spectroscopy, circular dichroism (CD), and Raman spectroscopy, have been used to study the structures and interactions of macromolecules, including DNA and proteins. Although RNAs harbor similar chemical modifications or structure-mediated functions, the number of RNA studies that employ biophysical approaches is scarce. In this viewpoint article, we present a biophysical perspective that links RNA methylation to structure and propose that FT-IR analyses can be employed to examine global changes in the abundance of cellular RNA m(6)A marks. Additionally, we discuss the potential applications of biophysical approaches that may be employed to gain insight into methylation-mediated changes in RNA structures.Article Salt Tolerance Potential of Selected Solanum Pennellii Introgression Lines: Unique Shoot and Root Responses(Wiley, 2025) Yildiz, Hatice Selale; Doganlar, Sami; Frary, AnneSalinity stress affects agricultural lands worldwide, causing serious yield losses. Investigation of the salinity response and tolerance mechanisms of crop plants and their wild relatives is important for developing tolerant varieties. In this study, three Solanum pennellii introgression lines (IL2-5, IL7-4-1, IL8-3), reported to be tolerant to abiotic stress, were investigated for their physiological and molecular responses to severe salinity (200 mM NaCl). The findings emphasized the variety of different responses that even highly genetically similar lines can have to stress. In IL2-5, a lack of significant root and shoot growth reduction due to salinity was associated with the up-regulation of vacuolar ion transporter genes (NHX1 and NHX3) and the lowest Na+ and Cl- accumulation in leaves, while beneficial K+ levels were preserved. In IL7-4-1, lateral root development was exceptionally strong compared to the other lines, with high Na+ and Cl- accumulation in leaves due to this unique root architecture. Despite this, the negative effects were lower on IL7-4-1's shoot growth than in IL8-3 and the control cultivar M82 due to effective reactive oxygen species management and increased superoxide gene expression. IL8-3's growth response was most similar to M82; however, it was better able to maintain beneficial K+ levels under salt stress. Overall, it was revealed that S. pennellii has multiple salt tolerance mechanisms associated with specific chromosomal segments and unique plant architecture. In addition to contributing to a better understanding of the mechanisms of salinity tolerance, these findings provide important information for increasing tolerance through targeted breeding.Article Storage Protein Allergen Sensitization Patterns in Children: Insights from Multiplex Microarray Profiling and Hierarchical Clustering(Wiley, 2025) Caka, Canan; Ozcivici, Engin; Karakus, Ceyda Oksel; Sekerel, Bulent EnisBackground Storage proteins (SPs), including 2S albumins, vicilins, and legumins, are key allergenic molecules (AMs) of peanuts, tree nuts (TNs), and sesame. Their structural stability contributes to allergenicity and sensitization. This study explored SP AM clustering patterns and evaluated the test performance of multiplex microarray (MM) testing in a pediatric cohort. Methods We retrospectively analyzed 350 children (median age: 3.7 years) with detectable SP sensitizations (>= 0.1 kU(A)/L) using the ALEX(2) MM platform. Sensitization interrelationships were analyzed using correlation heatmaps, hierarchical clustering (HC), dimensionality reduction, and feature elimination. Predictive utility was assessed through ROC curve analysis at different sensitization cut-offs (>0.1 and >0.3 kU(A)/L) and total IgE thresholds (>0, >20, and >50 kU/L). Results HC identified a broad SP cluster spanning peanuts, TNs, sesame, poppy seed, and buckwheat. Strong correlations and early HC linkages suggested extensive cross-sensitization (e.g., Ana o 3-Pis v 1 and Jug r 4-Cor a 9), alongside evidence of co-sensitization and molecular spreading. Unexpected clustering of structurally dissimilar peanut and pistachio AMs pointed to shared epitopes and/or cross-contamination. 2S albumins (Ara h 2, Cor a 14, Jug r 1, Ana o 3, and Ses i 1) were most predictive for clinical reactivity. Lower cut-offs and exclusion of patients with low total IgE improved test performance. Alpha-hairpinin (Pap s 2S albumin) showed potential as specific markers. Conclusions MM testing enables detailed SP sensitization profiling. Cluster-based interpretation may clarify cross- vs. co-sensitization, supporting informed clinical decisions. Use of recombinant AMs and IgE stratification may further enhance MM utility in food allergy diagnostics.Article Effect of Marination on the Formation of Polycyclic Aromatic Hydrocarbons in Grilled Vegetables(Wiley, 2025) Kacmaz Ozcetin, Sibel; Artok, LeventThe effect of marination on the formation of polycyclic aromatic hydrocarbons (PAH) in charcoal-grilled vegetables was studied. Various marinade ingredients, including apple cider vinegar, red grape vinegar, lemon juice, garlic powder, black pepper, and the food additive tert-butylhydroquinone (TBHQ) were applied to vegetable samples before charcoal grilling. The total phenolic content (TPC) and total antioxidant capacity (TAC) of each marinade ingredient were assessed for their contribution to PAH inhibition. A substantial decrease in PAH4 formation was observed in marinated vegetables. Red grape vinegar exhibited the strongest average inhibitory effect on total PAH4 formation (75%), followed by apple vinegar (68%), lemon juice (52%), garlic powder (34%), and black pepper (30%). Additionally, the TBHQ (67%) demonstrated a strong inhibitory effect, reducing total PAH4 formation by 67%. These findings offer valuable insights for reducing PAH levels in grilled vegetables and preventing their formation.Article Citation - WoS: 5Citation - Scopus: 5Magnetically Controllable and Degradable Milliscale Swimmers as Intraocular Drug Implants(Wiley, 2025) Yildiz, E.; Bozuyuk, U.; Yildiz, E.; Wang, F.; Han, M.; Karacakol, A.C.; Sitti, M.Intraocular drug implants are increasingly used for retinal treatments, such as age-related macular degeneration and diabetic macular edema, due to the rapidly aging global population. Although these therapies show promise in arresting disease progression and improving vision, intraocular implant-based therapies can cause unexpected complications that require further surgery due to implant dislocation or uncontrolled drug release. These frequent complications of intraocular drug implants can be overcome using magnetically controllable degradable milliscale swimmers (MDMS) with a double-helix body morphology. A biodegradable hydrogel, polyethylene glycol diacrylate, is employed as the primary 3D printing material of MDMS, and it is magnetized by decorating it with biocompatible polydopamine-encapsulated iron-platinum nanoparticles. MDMS have comparable dimensions to commercial intraocular implants that achieve translational motions in both aqueous and vitreous bodies. They can be imaged in real-time using optical coherence tomography, ultrasound, and photoacoustic imaging. Thanks to their biodegradable hydrogel-based structure, they can be loaded with anti-inflammatory drug molecules and release the medications without disrupting retinal epithelial viability and barrier function, and decrease proinflammatory cytokine release significantly. These magnetically controllable swimmers, which degrade in a couple of months, can be used for less invasive and more precise intraocular drug delivery compared to commercial intraocular drug implants. © 2025 The Author(s). Advanced Science published by Wiley-VCH GmbH.Article Citation - WoS: 1Citation - Scopus: 1Hn1 Functions in Protein Synthesis Regulation Via Mtor-Rps6 Axis and Maintains Nucleolar Integrity(Wiley, 2025) Ozduman, Guelseren; Javed, Aadil; Alasar, Azime Akcaoz; Akgul, Buenyamin; Korkmaz, Kemal SamiHaematological and Neurological Expressed 1 (HN1) is an oncogene for various cancers and previously has been linked with centrosome clustering and cell cycle pathways. Moreover, HN1 has recently been reported to activate mTOR signalling, which is the regulator of ribosome biogenesis and maintenance. We explored the role of HN1 in mTOR signalling through various gain- and loss-of-function experiments using biochemical approaches in different cell lines. We demonstrated for the first time that HN1 is required for nucleolar organiser region (NOR) integrity and function. Immunoprecipitation-based association and colocalization studies demonstrated that HN1 is an important component of the mTOR-RPS6 axis, and its depletion results with reduced mRNA translation in mammalian cancer cell lines. This study also demonstrated that the depletion of HN1 leads to the irregular distribution of nucleolar structures, potentially leading to cell cycle deregulation as reported previously. Accordingly, components of the translation machinery aggregate with a distinct speckled pattern, lose their essential interactions and ultimately impair mRNA translation efficiency when the HN1 is depleted. These results suggest that HN1 is an essential component of the nucleolus, required for ribosome biogenesis as well as global mRNA translation.Article Citation - WoS: 4Citation - Scopus: 5Near-Infrared Emissive Super Penetrating Conjugated Polymer Dots for Intratumoral Imaging in 3d Tumor Spheroid Models(Wiley, 2024) Karabacak, Soner; Coban, Basak; Yildiz, Ahu Arslan; Yildiz, Umit HakanThis study describes the formation of single-chain polymer dots (Pdots) via ultrasonic emulsification of nonionic donor-acceptor-donor type (D-A-D) alkoxy thiophene-benzobisthiadiazole-based conjugated polymers (Poly BT) with amphiphilic cetyltrimethylammonium bromide (CTAB). The methodology yields Pdots with a high cationic surface charge (+56.5 mV +/- 9.5) and average hydrodynamic radius of 12 nm. Optical characterization reveals that these Pdots emit near-infrared (NIR) light at a maximum wavelength of 860 nm owing to their conjugated polymer backbone consisting of D-A-D monomers. Both colloidal and optical properties of these Pdots make them promising fluorescence emissive probes for bioimaging applications. The significant advantage of positively charged Pdots is demonstrated in diffusion-limited mediums such as tissues, utilizing human epithelial breast adenocarcinoma, ATCC HTB-22 (MCF-7), human bone marrow neuroblastoma, ATCC CRL-2266 (SH-SY5Y), and rat adrenal gland pheochromocytoma, CRL-1721 (PC-12) tumor spheroid models. Fluorescence microscopy analysis of tumor spheroids from MCF-7, SH-SY5Y, and PC-12 cell lines reveals the intensity profile of Pdots, confirming extensive penetration into the central regions of the models. Moreover, a comparison with mitochondria staining dye reveals an overlap between the regions stained by Pdots and the dye in all three tumor spheroid models. These results suggest that single-chain D-A-D type Pdots, cationized via CTAB, exhibit long-range mean free path of penetration (approximate to 1 mu m) in dense mediums and tumors. The single chain near infrared (NIR) emissive Pdots with high cationic surface charge enable penetration in dense medium such as tumor spheroids. Both colloidal and optical properties of Pdots make them promising fluorescent probe in bioimaging. imageReview Citation - WoS: 4Citation - Scopus: 4Unraveling the Intriguing Interplay: Exploring the Role of Lncrnas in Caspase-Independent Cell Death(Wiley, 2024) Ciftci, Yusuf Cem; Akgül, Bünyamin; Vatansever, Ipek Erdogan; Akgul, BuenyaminCell death plays a crucial role in various physiological and pathological processes. Until recently, programmed cell death was mainly attributed to caspase-dependent apoptosis. However, emerging evidence suggests that caspase-independent cell death (CICD) mechanisms also contribute significantly to cellular demise. We and others have reported and functionally characterized numerous long noncoding RNAs (lncRNAs) that modulate caspase-dependent apoptotic pathways potentially in a pathway-dependent manner. However, the interplay between lncRNAs and CICD pathways has not been comprehensively documented. One major reason for this is that most CICD pathways have been recently discovered with some being partially characterized at the molecular level. In this review, we discuss the emerging evidence that implicates specific lncRNAs in the regulation and execution of CICD. We summarize the diverse mechanisms through which lncRNAs modulate different forms of CICD, including ferroptosis, necroptosis, cuproptosis, and others. Furthermore, we highlight the intricate regulatory networks involving lncRNAs, protein-coding genes, and signaling pathways that orchestrate CICD in health and disease. Understanding the molecular mechanisms and functional implications of lncRNAs in CICD may unravel novel therapeutic targets and diagnostic tools for various diseases, paving the way for innovative strategies in disease management and personalized medicine.Article Citation - WoS: 6Epitranscriptomics M<sup>6</Sup>a Analyses Reveal Distinct M<sup>6</Sup>a Marks Under Tumor Necrosis Factor Α (tnf-Α) Apoptotic Conditions in Hela Cells(Wiley, 2024) Akçaöz Alasar, Azime; Tüncel, Özge; Sağlam, Buket; Gazaloğlu, Yasemin; Atbinek, Melis; Çağıral, Umut; Akgül, BünyaminTumor necrosis factor-alpha (TNF-alpha) is a ligand that induces both intrinsic and extrinsic apoptotic pathways in HeLa cells by modulating complex gene regulatory mechanisms. However, the full spectrum of TNF-alpha-modulated epitranscriptomic m(6)A marks is unknown. We employed a genomewide approach to examine the extent of m(6)A RNA modifications under TNF-alpha-modulated apoptotic conditions in HeLa cells. miCLIP-seq analyses revealed a plethora of m(6)A marks on 632 target mRNAs with an enrichment on 99 mRNAs associated with apoptosis. Interestingly, the m(6)A RNA modification patterns were quite different under cisplatin- and TNF-alpha-mediated apoptotic conditions. We then examined the abundance and translational efficiencies of several mRNAs under METTL3 knockdown and/or TNF-alpha treatment conditions. Our analyses showed changes in the translational efficiency of TP53INP1 mRNA based on the polysome profile analyses. Additionally, TP53INP1 protein amount was modulated by METTL3 knockdown upon TNF-alpha treatment but not CP treatment, suggesting the existence of a pathway-specific METTL3-TP53INP1 axis. Congruently, METLL3 knockdown sensitized HeLa cells to TNF-alpha-mediated apoptosis, which was also validated in a zebrafish larval xenograft model. These results suggest that apoptotic pathway-specific m(6)A methylation marks exist in cells and TNF-alpha-METTL3-TP53INP1 axis modulates TNF-alpha-mediated apoptosis in HeLa cells.Article Citation - WoS: 6Citation - Scopus: 5Epitranscriptomics M6a Analyses Reveal Distinct M6a Marks Under Tumor Necrosis Factor Α (tnf-Α) Apoptotic Conditions in Hela Cells(Wiley, 2024) Akçaöz Alasar, Azime; Tuncel, Özge; Sağlam, Buket; Gazaloğlu, Yasemin; Atbinek, Melis; Çağıral, Umut; İşcan, Evin; Özhan, Güneş; Akgül, BünyaminTumor necrosis factor-alpha (TNF-alpha) is a ligand that induces both intrinsic and extrinsic apoptotic pathways in HeLa cells by modulating complex gene regulatory mechanisms. However, the full spectrum of TNF-alpha-modulated epitranscriptomic m(6)A marks is unknown. We employed a genomewide approach to examine the extent of m(6)A RNA modifications under TNF-alpha-modulated apoptotic conditions in HeLa cells. miCLIP-seq analyses revealed a plethora of m(6)A marks on 632 target mRNAs with an enrichment on 99 mRNAs associated with apoptosis. Interestingly, the m(6)A RNA modification patterns were quite different under cisplatin- and TNF-alpha-mediated apoptotic conditions. We then examined the abundance and translational efficiencies of several mRNAs under METTL3 knockdown and/or TNF-alpha treatment conditions. Our analyses showed changes in the translational efficiency of TP53INP1 mRNA based on the polysome profile analyses. Additionally, TP53INP1 protein amount was modulated by METTL3 knockdown upon TNF-alpha treatment but not CP treatment, suggesting the existence of a pathway-specific METTL3-TP53INP1 axis. Congruently, METLL3 knockdown sensitized HeLa cells to TNF-alpha-mediated apoptosis, which was also validated in a zebrafish larval xenograft model. These results suggest that apoptotic pathway-specific m(6)A methylation marks exist in cells and TNF-alpha-METTL3-TP53INP1 axis modulates TNF-alpha-mediated apoptosis in HeLa cells.