Publications without Fulltext
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3
Browse
91 results
Search Results
Publication Metadata only TW68, cryptochromes stabilizer, regulates fasting blood glucose levels in diabetic ob/ob and high fat-diet-induced obese mice(Pergamon-Elsevier Science Ltd, 2023) Gul, Seref; Akyel, Yasemin Kubra; Ipek, Ozgecan Savlug; Akarlar, Busra Aytul; Taskin, Ali Cihan; Goren, Ahmet Ceyhan; Baris, Ibrahim; Ozturk, Nuri; Guzel, Mustafa; Aydin, Cihan; Okyar, Alper; Department of Molecular Biology and Genetics; Sürme, Saliha; Ayva, Çağla Ergün; Gül, Zeynep Melis; Özcan, Onur; Türkay, Metin; Department of Molecular Biology and Genetics; College of Sciences; Graduate School of Sciences and EngineeringCryptochromes (CRYs), transcriptional repressors of the circadian clock in mammals, inhibit cAMP production when glucagon activates G-protein coupled receptors. Therefore, molecules that modulate CRYs have the po-tential to regulate gluconeogenesis. In this study, we discovered a new molecule called TW68 that interacts with the primary pockets of mammalian CRY1/2, leading to reduced ubiquitination levels and increased stability. In cell-based circadian rhythm assays using U2OS Bmal1-dLuc cells, TW68 extended the period length of the circadian rhythm. Additionally, TW68 decreased the transcriptional levels of two genes, Phosphoenolpyruvate carboxykinase 1 (PCK1) and Glucose-6-phosphatase (G6PC), which play crucial roles in glucose biosynthesis during glucagon-induced gluconeogenesis in HepG2 cells. Oral administration of TW68 in mice showed good tolerance, a good pharmacokinetic profile, and remarkable bioavailability. Finally, when administered to fasting diabetic animals from ob/ob and HFD-fed obese mice, TW68 reduced blood glucose levels by enhancing CRY stabilization and subsequently decreasing the transcriptional levels of Pck1 and G6pc. These findings collectively demonstrate the antidiabetic efficacy of TW68 in vivo, suggesting its therapeutic potential for controlling fasting glucose levels in the treatment of type 2 diabetes mellitus.Publication Metadata only EDA2R-NIK signaling in cancer cachexia(Lippincott Williams and Wilkins, 2024) Department of Molecular Biology and Genetics; Ağca, Samet; Kır, Serkan; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of SciencesPurpose of review Cachexia is a debilitating condition causing weight loss and skeletal muscle wasting that negatively influences treatment and survival of cancer patients. The objective of this review is to describe recent discoveries on the role of a novel signaling pathway involving ectodysplasin A2 receptor (EDA2R) and nuclear factor kappa B (NF kappa B)-inducing kinase (NIK) in muscle atrophy.Recent findingsStudies identified tumor-induced upregulation of EDA2R expression in muscle tissues in pre-clinical cachexia models and patients with various cancers. Activation of EDA2R by its ligand promoted atrophy in cultured myotubes and muscle tissue, which depended on NIK activity. The non-canonical NF kappa B pathway via NIK also stimulated muscle atrophy. Mice lacking EDA2R or NIK were protected from muscle loss due to tumors. Tumor-induced cytokine oncostatin M (OSM) upregulated EDA2R expression in muscles whereas OSM receptor-deficient mice were resistant to muscle wasting.SummaryRecent discoveries revealed a mechanism involving EDA2R-NIK signaling and OSM that drives cancer-associated muscle loss, opening up new directions for designing anti-cachexia treatments. The therapeutic potential of targeting this mechanism to prevent muscle loss should be further investigated. Future research should also explore broader implications of the EDA2R-NIK pathway in other muscle wasting diseases and overall muscle health.Publication Metadata only The role of interleukin-6 family cytokines in cancer cachexia(Wiley, 2024) Department of Molecular Biology and Genetics; Ağca, Samet; Kır, Serkan; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of SciencesCachexia is a wasting syndrome that manifests in more than half of all cancer patients. Cancer-associated cachexia negatively influences the survival of patients and their quality of life. It is characterized by a rapid loss of adipose and skeletal muscle tissues, which is partly mediated by inflammatory cytokines. Here, we explored the crucial roles of interleukin-6 (IL-6) family cytokines, including IL-6, leukemia inhibitory factor, and oncostatin M, in the development of cancer cachexia. These cytokines have been shown to exacerbate cachexia by promoting the wasting of adipose and muscle tissues, activating mechanisms that enhance lipolysis and proteolysis. Overlapping effects of the IL-6 family cytokines depend on janus kinase/signal transducer and activator of transcription 3 signaling. We argue that the blockade of these cytokine pathways individually may fail due to redundancy and future therapeutic approaches should target common downstream elements to yield effective clinical outcomes.Publication Metadata only Tumour-induced alterations in single-nucleus transcriptome of atrophying muscles indicate enhanced protein degradation and reduced oxidative metabolism(Wiley, 2024) Dag, Meric; Dogan, Sukru Anil; Department of Molecular Biology and Genetics; Ağca, Samet; Waraich, Aylin Domaniku; Bilgiç, Şevval Nur; Sucuoğlu, Melis; Kır, Serkan; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of SciencesBackground Tumour-induced skeletal muscle wasting in the context of cancer cachexia is a condition with profound implications for patient survival. The loss of muscle mass is a significant clinical obstacle and is linked to reduced tolerance to chemotherapy and increased frailty. Understanding the molecular mechanisms driving muscle atrophy is crucial for the design of new therapeutics.MethodsLewis lung carcinoma tumours were utilized to induce cachexia and muscle atrophy in mice. Single-nucleus libraries of the tibialis anterior (TA) muscle from tumour-bearing mice and their non-tumour-bearing controls were constructed using 10X Genomics applications following the manufacturer's guidelines. RNA sequencing results were analysed with Cell Ranger software and the Seurat R package. Oxygen consumption of mitochondria isolated from TA muscle was measured using an Oroboros O2k-FluoRespirometer. Mouse primary myotubes were treated with a recombinant ectodysplasin A2 (EDA-A2) protein to activate EDA-A2 receptor (EDA2R) signalling and study changes in gene expression and oxygen consumption.Results Tumour-bearing mice were sacrificed while exhibiting moderate cachexia. Average TA muscle weight was reduced by 11% (P = 0.0207) in these mice. A total of 12 335 nuclei, comprising 6422 nuclei from the control group and 5892 nuclei from atrophying muscles, were studied. The analysis of single-nucleus transcriptomes identified distinct myonuclear gene signatures and a shift towards type IIb myonuclei. Muscle atrophy-related genes, including Atrogin1, MuRF1 and Eda2r, were upregulated in these myonuclei, emphasizing their crucial roles in muscle wasting. Gene set enrichment analysis demonstrated that EDA2R activation and tumour inoculation led to similar expression patterns in muscle cells, including the stimulation of nuclear factor-kappa B, Janus kinase-signal transducer and activator of transcription and transforming growth factor-beta pathways and the suppression of myogenesis and oxidative phosphorylation. Muscle oxidative metabolism was suppressed by both tumours and EDA2R activation.ConclusionsThis study identified tumour-induced transcriptional changes in muscle tissue at single-nucleus resolution and highlighted the negative impact of tumours on oxidative metabolism. These findings contribute to a deeper understanding of the molecular mechanisms underlying muscle wasting.Publication Metadata only Bud14 function is crucial for spindle pole body size maintenance(TUBITAK, 2024) Department of Molecular Biology and Genetics; Girgin, Sevilay Münire; Çaydaşı, Ayşe Koca; Department of Molecular Biology and Genetics; College of Sciences; Graduate School of Sciences and EngineeringBackground/aim: Spindle pole bodies (SPB), the functional equivalent of centrosomes in yeast, duplicate through generation of a new SPB next to the old one. However, SPBs are dynamic structures that can grow and exchange, and mechanisms that regulate SPB size remain largely unknown. This study aims to elucidate the role of Bud14 in SPB size maintenance in Saccharomyces cerevisiae. Materials and methods: We employed quantitative fluorescence microscopy to assess the relative and absolute amounts of SPB structural proteins at SPBs of wildtype cells and in cells lacking BUD14 (bud14∆). Quantifications were performed using asynchronous cell cultures, as well as cultures synchronously progressing through the cell cycle and upon different cell cycle arrests. We also utilized mutants that allow the separation of Bud14 functions. Results: Our results indicate that higher levels of SPB inner, outer, and central plaque proteins are present at the SPBs of bud14∆ cells compared to wildtype cells during anaphase, as well as during nocodazole-induced M-phase arrest. However, during α-factor mediated G1 arrest, inner and outer plaque proteins responded differently to the absence of BUD14. A Bud14 mutant that cannot interact with the Protein Phosphatase 1 (Glc7) phenocopied bud14∆ in terms of SPB-bound levels of the inner plaque protein Spc110, whereas disruption of Bud14-Kel1-Kel2 complex did not alter Spc110 levels at SPBs. In cells synchronously released from α-factor arrest, lack of Bud14-Glc7 caused increase of Spc110 at the SPBs at early stages of the cell cycle. Conclusion: We identified Bud14 as a critical protein for SPB size maintenance. The interaction of Bud14 with Glc7, but not with the Kelch proteins, is indispensable for restricting levels of Spc110 incorporated into the SPBs. © TÜBİTAK.Publication Metadata only Ectodysplasin A2 receptor signaling in skeletal muscle pathophysiology(Elsevier Ltd, 2024) Department of Molecular Biology and Genetics; Özen, Sevgi Döndü; Kır, Serkan; Department of Molecular Biology and Genetics; College of Sciences; Graduate School of Sciences and EngineeringSkeletal muscle is essential in generating mechanical force and regulating energy metabolism and body temperature. Pathologies associated with muscle tissue often lead to impaired physical activity and imbalanced metabolism. Recently, ectodysplasin A2 receptor (EDA2R) signaling has been shown to promote muscle loss and glucose intolerance. Upregulated EDA2R expression in muscle tissue was associated with aging, denervation, cancer cachexia, and muscular dystrophies. Here, we describe the roles of EDA2R signaling in muscle pathophysiology, including muscle atrophy, insulin resistance, and aging-related sarcopenia. We also discuss the EDA2R pathway, which involves EDA-A2 as the ligand and nuclear factor (NF)κB-inducing kinase (NIK) as a downstream mediator, and the therapeutic potential of targeting these proteins in the treatment of muscle wasting and metabolic dysfunction. © 2024 Elsevier LtdPublication Metadata only Global repair is the primary nucleotide excision repair subpathway for the removal of pyrimidine-pyrimidone (6-4) damage from the arabidopsis genome(Nature Portfolio, 2024) Kaya, Sezgi; Sancar, Aziz; Adebali, Ogün; Department of Molecular Biology and Genetics; Erdoğan, Duğçar Ebrar; Öztaş, Onur; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of SciencesUltraviolet (UV) component of solar radiation impairs genome stability by inducing the formation of pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] in plant genomes. (6-4)PPs disrupt growth and development by interfering with transcription and DNA replication. To resist UV stress, plants employ both photoreactivation and nucleotide excision repair that excises oligonucleotide containing (6-4)PPs through two subpathways: global and transcription-coupled excision repair (TCR). Here, we analyzed the genome-wide excision repair-mediated repair of (6-4)PPs in Arabidopsis thaliana and found that (6-4)PPs can be repaired by TCR;however, the main subpathway to remove (6-4)PPs from the genome is global repair. Our analysis showed that open chromatin genome regions are more rapidly repaired than heterochromatin regions, and the repair level peaks at the promoter, transcription start site and transcription end site of genes. Our study revealed that the repair of (6-4)PP in plants showed a distinct genome-wide repair profile compared to the repair of other major UV-induced DNA lesion called cyclobutane pyrimidine dimers (CPDs).Publication Metadata only Lice (Phthiraptera, Amblycera, Ischnocera) collected on the birds in the Aras Basin in Iğdır Province, Türkiye with new records and new host associations(Springer, 2024) Dik, Bilal; Coban, Aysegul; Kirpik, Mehmet Ali; Keskin, Adem; Catalkaya, Begum; Coban, Emrah; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Department of Molecular Biology and Genetics; ; College of Sciences;Chewing lice (Phthiraptera, Ischnocera and Amblycera) are permanent ectoparasites of birds and primarly feed on the feathers and scales of birds. To detect the chewing lice species found on birds in Aras basin, Igdir, Turkiye, a total of 240 birds represented by 61 species belonging to 30 families in 13 orders were examined during the 2021 bird migration season. A total of 531 (186 females, 136 males and 209 nymphs) lice were collected from 75 individuals (31,25% of birds examined) of 26 species, 21 families and 10 orders. Thirty-one lice species (11 amblyceran and 20 ischnoceran species) in 22 genera were identified. Of these, 15 lice species were reported for the first time in Turkiye, namely Cuculiphilus fasciatus, Pseudomenopon qadrii, Philopterus sp., Ricinus serratus, Philopterus picae, Rostrinirmus buresi, Sturnidoecus sp., Philopterus excisus, Philopterus microsomaticus, Philopterus coarctatus, Brueelia fuscopleura, Sturnidoecus pastoris, Brueelia currucae, Penenirmus auritus and Strigiphilus tuleskovi. In addition, new host associations were reported for the lice species Kurodaia fulvofasciata, Degeeriella rufa and Myrsidea rustica.Publication Metadata only CilioGenics: an integrated method and database for predicting novel ciliary genes(Oxford Univ Press Inc, 2024) Pir, Mustafa S.; Yenisert, Ferhan; Demirci, Hasan C.; Korkmaz, Mustafa E.; Karaman, Asli; Tsiropoulou, Sofia; Blacque, Oliver E.; Oner, Sukru S.; Doluca, Osman; Cevik, Sebiha; Kaplan, Oktay, I; Department of Molecular Biology and Genetics; Begar, Efe; Karalar, Elif Nur Fırat; Department of Molecular Biology and Genetics; ; Graduate School of Sciences and Engineering; College of Sciences;Uncovering the full list of human ciliary genes holds enormous promise for the diagnosis of cilia-related human diseases, collectively known as ciliopathies. Currently, genetic diagnoses of many ciliopathies remain incomplete (). While various independent approaches theoretically have the potential to reveal the entire list of ciliary genes, approximately 30% of the genes on the ciliary gene list still stand as ciliary candidates (,). These methods, however, have mainly relied on a single strategy to uncover ciliary candidate genes, making the categorization challenging due to variations in quality and distinct capabilities demonstrated by different methodologies. Here, we develop a method called CilioGenics that combines several methodologies (single-cell RNA sequencing, protein-protein interactions (PPIs), comparative genomics, transcription factor (TF) network analysis, and text mining) to predict the ciliary capacity of each human gene. Our combined approach provides a CilioGenics score for every human gene that represents the probability that it will become a ciliary gene. Compared to methods that rely on a single method, CilioGenics performs better in its capacity to predict ciliary genes. Our top 500 gene list includes 258 new ciliary candidates, with 31 validated experimentally by us and others. Users may explore the whole list of human genes and CilioGenics scores on the CilioGenics database (https://ciliogenics.com/).Publication Metadata only Mammal responses to global changes in human activity vary by trophic group and landscape(Nature Portfolio, 2024) Burton, A. Cole; Beirne, Christopher; Gayno, Kaitlyn M.; Sun, Catherine; Granados, Alys; Allen, Maximilian L.; Alston, Jesse M.; Alvarenga, Guilherme C.; Calderon, Francisco Samuel Alvarez; Amir, Zachary; Anhalt-Depies, Christine; Appel, Cara; Arroyo-Arce, Stephanny; Balme, Guy; Bar-Massada, Avi; Barcelos, Daniele; Barr, Evan; Barthelmess, Erika L.; Baruzzi, Carolina; Basak, Sayantani M.; Beenaerts, Natalie; Belmaker, Jonathan; Belova, Olgirda; Bezarevic, Branko; Bird, Tori; Bogan, Daniel A.; Bogdanovic, Neda; Boyce, Andy; Boyce, Mark; Brandt, LaRoy; Brodie, Jedediah F.; Brooke, Jarred; Bubnicki, Jakub W.; Cagnacci, Francesca; Carr, Benjamin Scott; Carvalho, Joao; Casaer, Jim; Cerne, Rok; Chen, Ron; Chow, Emily; Churski, Marcin; Cincotta, Connor; Cirovic, Dusko; Coates, T. D.; Compton, Justin; Coon, Courtney; Cove, Michael V.; Crupi, Anthony P.; Dal Farra, Simone; Darracq, Andrea K.; Davis, Miranda; Dawe, Kimberly; De Waele, Valerie; Descalzo, Esther; Diserens, Tom A.; Drimaj, Jakub; Dul'a, Martin; Ellis-Felege, Susan; Ellison, Caroline; Ertürk, Alper; Fantle-Lepczyk, Jean; Favreau, Jorie; Fennell, Mitch; Ferreras, Pablo; Ferretti, Francesco; Fiderer, Christian; Finnegan, Laura; Fisher, Jason T.; Fisher-Reid, M. Caitlin; Flaherty, Elizabeth A.; Flezar, Ursa; Flousek, Jiri; Foca, Jennifer M.; Ford, Adam; Franzetti, Barbara; Frey, Sandra; Fritts, Sarah; Frybova, Sarka; Furnas, Brett; Gerber, Brian; Geyle, Hayley M.; Gimenez, Diego G.; Giordano, Anthony J.; Gomercic, Tomislav; Gompper, Matthew E.; Grabin, Diogo Maia; Gray, Morgan; Green, Austin; Hagen, Robert; Hagen, Robert; Hammerich, Steven; Hanekom, Catharine; Hansen, Christopher; Hasstedt, Steven; Hebblewhite, Mark; Heurich, Marco; Hofmeester, Tim R.; Hubbard, Tru; Jachowski, David; Jansen, Patrick A.; Jaspers, Kodi Jo; Jensen, Alex; Jordan, Mark; Kaizer, Mariane C.; Kelly, Marcella J.; Kohl, Michel T.; Kramer-Schadt, Stephanie; Krofel, Miha; Krug, Andrea; Kuhn, Kellie M.; Kuijper, Dries P. J.; Kuprewicz, Erin K.; Kusak, Josip; Kutal, Miroslav; Lafferty, Diana J. R.; LaRose, Summer; Lashley, Marcus; Lathrop, Richard; Lee, Thomas E., Jr.; Lepczyk, Christopher; Lesmeister, Damon B.; Licoppe, Alain; Linnell, Marco; Loch, Jan; Long, Robert; Lonsinger, Robert C.; Louvrier, Julie; Luskin, Matthew Scott; MacKay, Paula; Maher, Sean; Manet, Benoit; Mann, Gareth K. H.; Marshall, Andrew J.; Mason, David; McDonald, Zara; McKay, Tracy; McShea, William J.; Mechler, Matt; Miaud, Claude; Millspaugh, Joshua J.; Monteza-Moreno, Claudio M.; Moreira-Arce, Dario; Mullen, Kayleigh; Nagy, Christopher; Naidoo, Robin; Namir, Itai; Nelson, Carrie; O'Neill, Brian; O'Mara, M. Teague; Oberosler, Valentina; Osorio, Christian; Ossi, Federico; Palencia, Pablo; Pearson, Kimberly; Pedrotti, Luca; Pekins, Charles E.; Pendergast, Mary; Pinho, Fernando F.; Plhal, Radim; Pocasangre-Orellana, Xochilt; Price, Melissa; Procko, Michael; Proctor, Mike D.; Ramalho, Emiliano Esterci; Ranc, Nathan; Reljic, Slaven; Remine, Katie; Rentz, Michael; Revord, Ronald; Reyna-Hurtado, Rafael; Risch, Derek; Ritchie, Euan G.; Romero, Andrea; Rota, Christopher; Rovero, Francesco; Rowe, Helen; Rutz, Christian; Salvatori, Marco; Sandow, Derek; Schalk, Christopher M.; Scherger, Jenna; Schipper, Jan; Scognamillo, Daniel G.; Semenzato, Paola; Sevin, Jennifer; Shamon, Hila; Shier, Catherine; Silva-Rodriguez, Eduardo A.; Sindicic, Magda; Smyth, Lucy K.; Soyumert, Anil; Sprague, Tiffany; St Clair, Colleen Cassady; Stenglein, Jennifer; Stephens, Philip A.; Stepniak, Kinga Magdalena; Stevens, Michael; Stevenson, Cassondra; Ternyik, Balint; Thomson, Ian; Torres, Rita T.; Tremblay, Joan; Urrutia, Tomas; Vacher, Jean-Pierre; Visscher, Darcy; Webb, Stephen L.; Weber, Julian; Weiss, Katherine C. B.; Whipple, Laura S.; Whittier, Christopher A.; Whittington, Jesse; Wierzbowska, Izabela; Wikelski, Martin; Williamson, Jacque; Wilmers, Christopher C.; Windle, Todd; Wittmer, Heiko U.; Zharikov, Yuri; Zorn, Adam; Kays, Roland.; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Department of Molecular Biology and Genetics; ; College of Sciences;Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human-wildlife interactions along gradients of human influence. Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.