Publications with Fulltext
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD(Nature Publishing Group (NPG), 2022) Günsel, Gizem Güneş; Conlon, Thomas M.; Jeridi, Aicha; Kim, Rinho; Ertuez, Zeynep; Lang, Niklas J.; Ansari, Meshal; Novikova, Mariia; Jiang, Dongsheng; Strunz, Maximilian; Gaianova, Mariia; Hollauer, Christine; Gabriel, Christina; Angelidis, Ilias; Doll, Sebastian; Pestoni, Jeanine C.; Edelmann, Stephanie L.; Kohlhepp, Marlene Sophia; Guillot, Adrien; Bassler, Kevin; Van Eeckhoutte, Hannelore P.; Kanashova, Tamara; Rodius, Sophie; Ballester-Lopez, Carolina; Robles, Carlos M. Genes; Smirnova, Natalia; Rehberg, Markus; Agarwal, Charu; Krikki, Ioanna; Piavaux, Benoit; Verleden, Stijn E.; Vanaudenaerde, Bart; Koenigshoff, Melanie; Dittmar, Gunnar; Bracke, Ken R.; Schultze, Joachim L.; Watz, Henrik; Eickelberg, Oliver; Stoeger, Tobias; Burgstaller, Gerald; Tacke, Frank; Heissmeyer, Vigo; Rinkevich, Yuval; Schiller, Herbert B.; Conrad, Marcus; Schneider, Robert; Kayalar, Özgecan; Konyalılar, Nur; Bayram, Hasan; Yıldırım, Ali Önder; Researcher; PhD Student; Faculty Member; Other; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; N/A; N/A; 4890; N/AExtravasation of monocytes into tissue and to the site of injury is a fundamental immunological process, which requires rapid responses via post translational modifications (PTM) of proteins. Protein arginine methyltransferase 7 (PRMT7) is an epigenetic factor that has the capacity to mono-methylate histones on arginine residues. Here we show that in chronic obstructive pulmonary disease (COPD) patients, PRMT7 expression is elevated in the lung tissue and localized to the macrophages. In mouse models of COPD, lung fibrosis and skin injury, reduced expression of PRMT7 associates with decreased recruitment of monocytes to the site of injury and hence less severe symptoms. Mechanistically, activation of NF-kappa B/RelA in monocytes induces PRMT7 transcription and consequential mono-methylation of histones at the regulatory elements of RAP1A, which leads to increased transcription of this gene that is responsible for adhesion and migration of monocytes. Persistent monocyte-derived macrophage accumulation leads to ALOX5 over-expression and accumulation of its metabolite LTB4, which triggers expression of ACSL4 a ferroptosis promoting gene in lung epithelial cells. Conclusively, inhibition of arginine mono-methylation might offer targeted intervention in monocyte-driven inflammatory conditions that lead to extensive tissue damage if left untreated. Chronic obstructive pulmonary disease is a progressive and incurable chronic condition that involves accumulation of inflammatory macrophages in the lung tissue. Authors here show in mouse models of lung disease that PRMT7, a protein arginine methyltransferase, is an important regulator of recruitment and the pro-inflammatory phenotype of macrophages.Publication Open Access Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice(Nature Portfolio, 2022) Akyel, Yasemin Kübra; Korkmaz, Tuba; Selvi, Saba; Danış, İbrahim; İpek, Özgecan Savluğ; Aygenli, Fatih; Öztürk, Nuri; Öztürk, Narin; Ünal, Durişehvar Özer; Güzel, Mustafa; Okyar, Alper; N/A; Department of Chemical and Biological Engineering; Department of Industrial Engineering; Gül, Şeref; Gül, Zeynep Melis; Işın, Şafak; Özcan, Onur; Akarlar, Büşra; Taşkın, Ali Cihan; Türkay, Metin; Kavaklı, İbrahim Halil; Researcher; Other; Faculty Member; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Industrial Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; N/A; N/A; N/A; N/A; N/A; 291296; 105301; 24956; 40319Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53(-/-) mice by similar to 25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on the p53 mutation.Publication Open Access Cross-linguistic patterns in the acquisition of quantifiers(National Academy of Sciences, 2016) Katsos, Napoleon; Cummins, Chris; Ezeizabarrena, Maria-Jose; Gavarro, Anna; Kraljevic, Jelena Kuvac; Hrzica, Gordana; Grohmann, Kleanthes K.; Skordi, Athina; de Lopez, Kristine Jensen; Sundahl, Lone; van Hout, Angeliek; Hollebrandse, Bart; Overweg, Jessica; Faber, Myrthe; van Koert, Margreet; Smith, Nafsika; Vija, Maigi; Zupping, Sirli; Kunnari, Sari; Morisseau, Tiffany; Rusieshvili, Manana; Yatsushiro, Kazuko; Fengler, Anja; Varlokosta, Spyridoula; Konstantzou, Katerina; Farby, Shira; Guasti, Maria Teresa; Vernice, Mirta; Okabe, Reiko; Isobe, Miwa; Crosthwaite, Peter; Hong, Yoonjee; Balciuniene, Ingrida; Nizar, Yanti Marina Ahmad; Grech, Helen; Gatt, Daniela; Cheong, Win Nee; Asbjornsen, Arve; Torkildsen, Janne von Koss; Haman, Ewa; Miekisz, Aneta; Gagarina, Natalia; Puzanova, Julia; Andelkovic, Darinka; Savic, Maja; Josic, Smiljana; Slancova, Daniela; Kapalkova, Svetlana; Barberan, Tania; Hassan, Saima; Chan, Cecilia Yuet Hung; Okubo, Tomoya; van der Lely, Heather; Sauerland, Uli; Noveck, Ira; Department of Psychology; Özge, Duygu; Department of Psychology; College of Social Sciences and HumanitiesLearners of most languages are faced with the task of acquiring words to talk about number and quantity. Much is known about the order of acquisition of number words as well as the cognitive and perceptual systems and cultural practices that shape it. Substantially less is known about the acquisition of quantifiers. Here, we consider the extent to which systems and practices that support number word acquisition can be applied to quantifier acquisition and conclude that the two domains are largely distinct in this respect. Consequently, we hypothesize that the acquisition of quantifiers is constrained by a set of factors related to each quantifier's specific meaning. We investigate competence with the expressions for "all," "none," "some," "some. not," and "most" in 31 languages, representing 11 language types, by testing 768 5-y-old children and 536 adults. We found a cross-linguistically similar order of acquisition of quantifiers, explicable in terms of four factors relating to their meaning and use. In addition, exploratory analyses reveal that language-and learner-specific factors, such as negative concord and gender, are significant predictors of variation.Publication Open Access De novo mutations in Plxnd1 and Rev3l cause mobius syndrome(Nature Publishing Group (NPG), 2015) Tomas-Roca, Laura; Tsaalbi-Shtylik, Anastasia; Jansen, Jacob G.; Singh, Manvendra K.; Epstein, Jonathan A.; Altunoglu, Umut; Verzijl, Harriette; Soria, Laura; van Beusekom, Ellen; Roscioli, Tony; Iqbal, Zafar; Gilissen, Christian; Hoischen, Alexander; de Brouwer,Arjan P. M.; Erasmus, Corrie; Schubert, Dirk; Brunner, Han; Aytes, Antonio Perez; Marin, Faustino; Aroca, Pilar; Carta, Arturo; de Wind, Niels; Padberg, George W.; van Bokhoven, Hans; N/A; Kayserili, Hülya; Other; School of Medicine; 7945Mobius syndrome (MBS) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The aetiology of this syndrome has been enigmatic since the initial descriptions by von Graefe in 1880 and by Mobius in 1888, and it has been debated for decades whether MBS has a genetic or a non-genetic aetiology. Here, we report de novo mutations affecting two genes, PLXND1 and REV3L in MBS patients. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA, respectively. Interestingly, analysis of Plxnd1 and Rev3l mutant mice shows that disruption of these separate pathways converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation. The finding that PLXND1 and REV3L mutations are responsible for a proportion of MBS patients suggests that de novo mutations in other genes might account for other MBS patients.Publication Open Access Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication(Nature Portfolio, 2021) Yurtman, Erinç; Özer, Onur; Yüncü, Eren; Dağtaş, Nihan Dilşad; Koptekin, Dilek; Çakan, Yasin Gökhan; Özkan, Mustafa; Akbaba, Ali; Kaptan, Damla; Atağ, Gözde; Vural, Kıvılcım Başak; Gündem, Can Yümni; Martin, Louise; Kılınç, Gülşah Merve; Ghalichi, Ayshin; Açan, Sinan Can; Yaka, Reyhan; Sağlıcan, Ekin; Lagerholm, Vendela Kempe; Krzewinska, Maja; Gunther, Torsten; Miranda, Pedro Morell; Pişkin, Evangelia; Sevketoğlu, Müge; Bilgin, C. Can; Atakuman, Ciğdem; Erdal, Yılmaz Selim; Sürer, Elif; Altınışık, N. Ezgi; Lenstra, Johannes A.; Yorulmaz, Sevgi; Abazari, Mohammad Foad; Hoseinzadeh, Javad; Baird, Douglas; Bıcakcı, Erhan; Çevik, Özlem; Gerritsen, Fokke; Gotherstrom, Anders; Somel, Mehmet; Togan, İnci; Özer, Füsun; Department of Archeology and History of Art; Özbal, Rana; Faculty Member; Department of Archeology and History of Art; College of Social Sciences and Humanities; 55583Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.Publication Open Access Bioabsorbable polymer optical waveguides for deep-tissue photomedicine(Nature Publishing Group (NPG), 2016) Gather, Malte C.; Humar, Matjaz; Choi, Myunghwan; Kim, Seonghoon; Kim, Ki Su; Hahn, Sei Kwang; Scarcelli, Giuliano; Randolph, Mark; Redmond, Robert W.; Yun, Seok Hyun.; Department of Electrical and Electronics Engineering; Nizamoğlu, Sedat; Faculty Member; Department of Electrical and Electronics Engineering; College of Engineering; 130295Advances in photonics have stimulated significant progress in medicine, with many techniques now in routine clinical use. However, the finite depth of light penetration in tissue is a serious constraint to clinical utility. Here we show implantable light-delivery devices made of bio-derived or biocompatible, and biodegradable polymers. In contrast to conventional optical fibres, which must be removed from the body soon after use, the biodegradable and biocompatible waveguides may be used for long-term light delivery and need not be removed as they are gradually resorbed by the tissue. As proof of concept, we demonstrate this paradigm-shifting approach for photochemical tissue bonding (PTB). Using comb-shaped planar waveguides, we achieve a full thickness ( 410 mm) wound closure of porcine skin, which represents similar to 10-fold extension of the tissue area achieved with conventional PTB. The results point to a new direction in photomedicine for using light in deep tissues.Publication Open Access Transmissive silicon photonic dichroic filters with spectrally selective waveguides(Nature Publishing Group (NPG), 2018) Li, Nanxi; Raval, Manan; Poulton, Christopher V.; Ruocco, Alfonso; Singh, Neetesh; Vermeulen, Diedrik; Ippen, Erich P.; Kolodziejski, Leslie A.; Watts, Michael R.; Department of Electrical and Electronics Engineering; Mağden, Emir Salih; Department of Electrical and Electronics Engineering; College of Engineering; 276368Many optical systems require broadband filters with sharp roll-offs for efficiently splitting or combining light across wide spectra. While free space dichroic filters can provide broadband selectivity, on-chip integration of these high-performance filters is crucial for the scalability of photonic applications in multi-octave interferometry, spectroscopy, and wideband wavelength-division multiplexing. Here we present the theory, design, and experimental characterization of integrated, transmissive, 1 x 2 port dichroic filters using spectrally selective waveguides. Mode evolution through adiabatic transitions in the demonstrated filters allows for single cutoff and flat-top responses with low insertion losses and octave-wide simulated bandwidths. Filters with cutoffs around 1550 and 2100 nm are fabricated on a silicon-on-insulator platform with standard complementary metal-oxide-semiconductor processes. A filter roll-off of 2.82 dB nm(-1) is achieved while maintaining ultra-broadband operation. This new class of nanophotonic dichroic filters can lead to new paradigms in on-chip communications, sensing, imaging, optical synthesis, and display applications.Publication Open Access The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration(Nature Portfolio, 2022) Opie-Martin, Sarah; Iacoangeli, Alfredo; Topp, Simon D.; Abel, Olubunmi; Mayl, Keith; Mehta, Puja R.; Shatunov, Aleksey; Fogh, Isabella; Bowles, Harry; Limbachiya, Naomi; Spargo, Thomas P.; Al-Khleifat, Ahmad; Williams, Kelly L.; Jockel-Balsarotti, Jennifer; Bali, Taha; Self, Wade; Henden, Lyndal; Nicholson, Garth A.; Ticozzi, Nicola; McKenna-Yasek, Diane; Tang, Lu; Shaw, Pamela J.; Chio, Adriano; Ludolph, Albert; Weishaupt, Jochen H.; Landers, John E.; Glass, Jonathan D.; Mora, Jesus S.; Robberecht, Wim; Van Damme, Philip; McLaughlin, Russell; Hardiman, Orla; van den Berg, Leonard; Veldink, Jan H.; Corcia, Phillippe; Stevic, Zorica; Siddique, Nailah; Silani, Vincenzo; Blair, Ian P.; Fan, Dong-sheng; Esselin, Florence; de la Cruz, Elisa; Camu, William; Siddique, Teepu; Miller, Timothy; Brown, Robert H.; Al-Chalabi, Ammar; Shaw, Christopher E.; Başak, Ayşe Nazlı; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 1512Superoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this international, retrospective observational study, we compare phenotypic and demographic characteristics between people with SOD1-ALS and people with ALS and no recorded SOD1 variant. We investigate which variants are associated with age at symptom onset and time from onset to death or censoring using Cox proportional-hazards regression. The SOD1-ALS dataset reports age of onset for 1122 and disease duration for 883 people; the comparator population includes 10,214 and 9010 people respectively. Eight variants are associated with younger age of onset and distinct survival trajectories; a further eight associated with younger onset only and one with distinct survival only. Here we show that onset and survival are decoupled in SOD1-ALS. Future research should characterise rarer variants and molecular mechanisms causing the observed variability. Analysis of age of onset and disease duration in a large, international cohort of people with SOD1-ALS shows that there is a distinct phenotype and that onset and progression are decoupled.Publication Open Access High thermoelectric performance enabled by convergence of nested conduction bands in Pb7Bi4Se13 with low thermal conductivity(Nature Publishing Group (NPG), 2021) Hu, Lei; Fang, Yue Wen; Qin, Feiyu; Cao, Xun; Zhao, Xiaoxu; Luo, Yubo; Repaka, Durga Venkata Maheswar; Luo, Wenbo; Suwardi, Ady; Soldi, Thomas; Huang, Yizhong; Liu, Zheng; Hippalgaonkar, Kedar; Snyder, G. Jeffrey; Xu, Jianwei; Yan, Qingyu; Department of Chemistry; Aydemir, Umut; Faculty Member; Department of Chemistry; Koç University AKKİM Boron-Based Materials _ High-technology Chemicals Research _ Application Center (KABAM) / Koç Üniversitesi AKKİM Bor Tabanlı Malzemeler ve İleri Teknoloji Kimyasallar Uygulama ve Araştırma Merkezi (KABAM); College of Sciences; 58403Thermoelectrics enable waste heat recovery, holding promises in relieving energy and environmental crisis. Lillianite materials have been long-term ignored due to low thermoelectric efficiency. Herein we report the discovery of superior thermoelectric performance in Pb7Bi4Se13 based lillianites, with a peak figure of merit, zT of 1.35 at 800 K and a high average zT of 0.92 (450-800 K). A unique quality factor is established to predict and evaluate thermoelectric performances. It considers both band nonparabolicity and band gaps, commonly negligible in conventional quality factors. Such appealing performance is attributed to the convergence of effectively nested conduction bands, providing a high number of valley degeneracy, and a low thermal conductivity, stemming from large lattice anharmonicity, low-frequency localized Einstein modes and the coexistence of high-density moire fringes and nanoscale defects. This work rekindles the vision that Pb7Bi4Se13 based lillianites are promising candidates for highly efficient thermoelectric energy conversion.Publication Open Access Evaluation of the cell behavior and growth characteristics of the porcine dermal xenograft patch in relation to the surface properties(Frontiers, 2022) Aydemir, Duygu; Eren, İlker; Demirhan, Mehmet; Ulusu, Nuriye Nuray; PhD Student; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; N/A; 168021; 9892; 6807NA
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