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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3

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    Splicing variants of versican in CD133+/CD44+ prostate cancer stem cells
    (Elsevier GMBH, 2024) Ayla, Sule; Karakoc, Emre; Byrne, Yasemin Yozgat; Parlayan, Cuneyd; Keskin, Ilknur; Taskiran, Aysegul; Oktem, Gulperi; Karahüseyinoğlu, Serçin;  ; School of Medicine;  
    A cancer mass is composed of a heterogeneous group of cells, a small part of which constitutes the cancer stem cells since they are less differentiated and have a high capacity to develop cancer. Versican is an extracellular matrix protein located in many human tissues. The mRNA of versican has been shown to have "splicing patterns" as detected by RT-PCR, northern blot analysis, and cDNA sequencing. Based on this knowledge this study aims to reveal the splice variants of versican molecules, which are thought to be involved in the pathogenesis of the DU145 human prostatic carcinoma cell line and prostatic cancer stem cells isolated from this cell line. In this study, RWPE-1 normal prostatic and DU-145 human prostate cancer cell lines have been used. Prostatic cancer stem cells and the remaining group of non-prostatic-cancer stem cells (bulk population) were isolated according to their CD133+/CD44+. RNA was isolated in all groups, and sequence analysis was accomplished for splicing variants by Illumina NextSeq 500 sequencing system. The results were analyzed by bioinformatic evaluation. As five isoforms of the versican gene in the differential transcript expression are analyzed, it was observed that a significant change was only found in the isoforms Versican 0 and Versican 1. In this study, we explored the function of this molecule which we think to be effective in cancer progression, and suggested that more valuable results can be obtained after the accomplishment of in vivo experiments.
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    Graph domain adaptation with localized graph signal representations
    (Elsevier GMBH, 2024) Pilavci, Yusuf Yigit; Guneyi, Eylem Tugce; Vural, Elif; Cengiz, Cemil;  ; Graduate School of Sciences and Engineering;  
    In this paper we propose a domain adaptation algorithm designed for graph domains. Given a source graph with many labeled nodes and a target graph with few or no labeled nodes, we aim to estimate the target labels by making use of the similarity between the characteristics of the variation of the label functions on the two graphs. Our assumption about the source and the target domains is that the local behavior of the label function, such as its spread and speed of variation on the graph, bears resemblance between the two graphs. We estimate the unknown target labels by solving an optimization problem where the label information is transferred from the source graph to the target graph based on the prior that the projections of the label functions onto localized graph bases be similar between the source and the target graphs. In order to efficiently capture the local variation of the label functions on the graphs, spectral graph wavelets are used as the graph bases. Experimentation on various data sets shows that the proposed method yields quite satisfactory classification accuracy compared to reference domain adaptation methods.
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    Indium-based quantum dots trapped in solid-state matrices: a one-pot synthesis, thermoresponsive properties, and enhanced micropollutant removal
    (Royal Society of Chemistry, 2024) Ük, Nida; Aykut, Sümeyye; Nar, Ilgın; Ünlü, Caner; Jahangiri, Hadi; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM);  ;  
    Indium-based quantum dots (QDs), such as copper indium disulfide and zinc copper indium sulfide, have been the center of research for decades due to their low toxicity and unique photophysical properties. In contrast, versatile indium-based materials like In2S3 and ZnIn2S4 have been rarely studied in their QD form because of the challenges in their synthesis and used in solid-state material based applications because of their colloidal nature. In this study, a one-pot single-step method to synthesize In2S3, ZnIn2S4, and Cu-doped ZnIn2S4 QDs trapped in insoluble solid-state oleic acid matrices was developed. The QDs in solid-state matrices exhibited bright orange colored fluorescence with controllable emission properties achieved by altering the chemical composition. Among these QDs, the ZnIn2S4 QDs displayed thermo-responsive properties. As the temperature increased, the fluorescence intensity of ZnIn2S4 QDs decreased. In addition, all QDs demonstrated high removal efficiency for micropollutants in the aqueous medium, especially against cationic organic dyes. This study represents one of the first attempts at the direct development of QDs trapped in insoluble solid-state matrices. The QDs in solid-state matrices hold promise for applications in thermal sensors and studies related to the micropollutant removal. © 2024 The Royal Society of Chemistry.
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    SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation
    (Nature Portfolio, 2024) Beillard, Emmanuel; Kayhan, Cavit Kerem; Bosco, Luca; Steindl, Katharina; Richter, Manuela Friederike; Bademci, Guney; Rauch, Anita; Fattahi, Zohreh; Valentino, Maria Lucia; Connolly, Anne M.; Bahr, Angela; Viola, Laura; Bergmann, Anke Katharina; Rocha, Maria Eugenia; Peart, Leshon; Castro-Rojas, Derly Liseth; Bueltmann, Eva; Khan, Suliman; Giarrana, Miriam Liliana; Teleanu, Raluca Ioana; Gonzalez, Joanna Michelle; Pini, Antonella; Schadlich, Ines Sophie; Vill, Katharina; Brugger, Melanie; Zuchner, Stephan; Pinto, Andreia; Donkervoort, Sandra; Bivona, Stephanie Ann; Riza, Anca; Streata, Ioana; Glaeser, Dieter; Baquero-Montoya, Carolina; Garcia-Restrepo, Natalia; Kotzaeridou, Urania; Brunet, Theresa; Epure, Diana Anamaria; Bertoli-Avella, Aida; Kariminejad, Ariana; Tekin, Mustafa; von Hardenberg, Sandra; Boennemann, Carsten G.; Stettner, Georg M.; Zanni, Ginevra; Nashabat, Marwan; Nabavizadeh, Nasrinsadat; Saraçoğlu, Hilal Pırıl; Sarıbaş, Burak; Avcı, Şahin; Börklü Yücel, Esra; Yılmaz, Elanur; Uygur, Seyide Ecesu; Eren, Zeynep Bengi; Kayserili, Hülya; Beillard, Nathalie Sonia Escande; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; Graduate School of Health Sciences; School of Medicine; Koç University Hospital
    SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients' primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.
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    A study on the early metabolic effects of salt and fructose consumption: the protective role of water
    (Springer, 2024) Hasbal, Nuri Barış; Siriopol, Dimitrie; Sanchez-Lozada, Laura G.; Lanaspa, Miguel A.; Johnson, Richard J.; Bakır, Çiçek Nur; İncir, Said; Kanbay, Mehmet;  ; School of Medicine;  
    Increasing serum osmolality has recently been linked with acute stress responses, which over time can lead to increased risk for obesity, hypertension, and other chronic diseases. Salt and fructose are two major stimuli that can induce acute changes in serum osmolality. Here we investigate the early metabolic effects of sodium and fructose consumption and determine whether the effects of sodium or fructose loading can be mitigated by blocking the change in osmolality with hydration. Forty-four healthy subjects without disease and medication were recruited into four groups. After overnight fasting, subjects in Group 1 drank 500 mL of salty soup, while those in Group 2 drank 500 mL of soup without salt for 15 min. Subjects in Group 3 drank 500 mL of 100% apple juice in 5 min, while subjects in Group 4 drank 500 mL of 100% apple juice and 500 mL of water in 5 min. Blood pressure (BP), plasma sodium, and glucose levels were measured every 15 min in the first 2 h. Serum and urine osmolarity, serum uric acid, cortisol, fibroblast growth factor 21 (FGF21), aldosterone, adrenocorticotropic hormone (ACTH) level, and plasma renin activity (PRA) were measured at the baseline and 2 h. Both acute intake of salt or fructose increased serum osmolality (maximum similar to 4 mOsm/L peaking at 75 min) associated with a rise in systolic and diastolic BP, PRA, aldosterone, ACTH, cortisol, plasma glucose, uric acid, and FGF21. Salt tended to cause greater activation of the renin-angiotensin-system (RAS), while fructose caused a greater rise in glucose and FGF21. In both cases, hydration could prevent the osmolality and largely block the acute stress response. Acute changes in serum osmolality can induce remarkable activation of the ACTH-cortisol, RAS, glucose metabolism, and uric acid axis that is responsive to hydration. In addition to classic dehydration, salt, and fructose-containing sugars can activate these responses. Staying well hydrated may provide benefits despite exposure to sugar and salt. More studies are needed to investigate whether hydration can block the chronic effects of sugar and salt on disease.